Automation is the key to future advances, says the Head of the … – National Health Executive

Below, Lee highlights how his passion for stem cell research brought him to the UKSCB, its role in the development of advanced therapeutics and discusses how automation and machine learning in the manufacturing process could mean faster patient access to stem cell therapies in the future.

My career has been hugely varied, taking me around the world across the public, private and academic sectors, but one thing has remained constant: my fascination with cell and gene therapies, and through research, bringing these closer to patients.

Ive been lucky enough to study cell and gene therapies in many different ways over the last twenty years, from the potential of stem cells as a therapy for Type I Diabetes and the role of genes in the cancer cell cycle, to perfecting techniques that differentiate stem cells into precursors for adult blood cells for transfusion therapies. But theres always more to discover.

One application that excites me the most is the use of stem cells for immuno-oncology, where immune cells are used to treat cancer. Were now able to take immune cells from donors and use gene modification so they can fight cancer in patients where they would normally be rejected.

These stem cells can provide an unlimited supply of cancer-fighting T cells, available off-the-shelf to treat anyone quickly when referred to a clinic. This living drug has the potential to constantly adapt to cancer, combating resistance, and existing within patients to continue fighting the disease indefinitely.

In fact, this simplest form of cell can become almost any cell type for many applications in cell therapies, and the UKs national repository for all human embryonic stem cell lines derived within the UK, is here, at the MHRAs UK Stem Cell Bank.

Established 20 years ago to curate all human embryonic stem cells created in the UK and to regulate their use and provision for research and in the clinic, the UKSCB at the MHRAs South Mimms Laboratories is now recognised globally as a leading repository with over 180 different human embryonic stem cell lines.

During this time, weve received support from the Medical Research Council (MRC) and National Institute for Health Research (NIHR) to deliver our banking activities and, together with the lines available for research, weve banked over 30 lines now available for clinical application, making the UKSCB the largest source of clinical grade human embryonic stem cells in the world.

As part of the MHRA, the UKSCB plays an important role in providing regulatory guidance and workshops to the stem cell health sector across the UK, and weve established links with Harvard University to support international training programmes.

The UKSCB is a unique asset within the MHRA, sitting at the forefront of the advanced therapies landscape in the UK, and Im eager to build on its great history and legacy at a time where were only just starting to realise the full potential and application of advanced cell therapies.

As an aging population, we can expect to receive novel treatments for disease in the form of small molecules and prescription drugs but often these only serve to manage symptoms or limit disease progression. Using stem cells, we can now develop replacement joints, neurons for improved brain function and even entire hearts can be made in the lab without the need for human donors.

But what can we do to keep up with demand and ensure quality? The UKSCB has contributed to over 100 publications in international peer reviewed journals, establishing strong links with the World Health Organisation and international partners to improve standards and controls. Weve recently completed a successful international collaboration with Japanese partners, Sinfonia, to trial their automated cell processing robot and we aim to continue with these efforts towards the cost-effective scaling up of our manufacturing.

I believe that future improvements in customer service lies in automation. Reliance on scientists for the manufacture of stem cells is labour intensive, expensive and introduces human error. Automation will alleviate a lot of the manual aspects of cell culture, allowing us to scale-up manufacturing, drive down costs and ensure the highest quality and consistency, allowing stem cell-derived advanced therapies to be more accessible to patients and affordable for healthcare systems. By introducing automation into this process, we can free-up capacity for our leading experts to move away from labour-intensive manufacturing and instead work on improving and adapting novel advanced therapies.

When I look at my role as the third custodian of the UKSCB I hope to build on the significant past achievements of Glyn Stacey and Elsa Abranches that have established us as the leading stem cell institution in the UK today. I hope to move us forward with a sustainable business model that secures the long-term viability of the UKSCB. This means expanding our operations across various cell therapy platforms, supporting the development of specific cell types for use in human cell therapies, and developing new standards, enabling regulatory approval and eventual uptake by healthcare organisations.

I also want the UKSCB to continue making an impact around the world, supporting the development of stem cell therapies and reference materials for advanced therapies with the World Health Organisation. Over the last twenty years, weve delivered more than 370 cell line vials to 25 different countries for research, and in 2022, 54% of the stem cell lines requested have been of clinical grade, rising year on year. I want to see this trend continue as demand for these lines as starting materials for cell therapies grows further.

The future of the MHRAs UKSCB is diverse and exciting and, much like the cells we curate, there are endless possibilities for us to support research and clinical advances in the UK and around the world. I cannot wait to see where the next 20 years will take us.

Image credit: iStock

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Automation is the key to future advances, says the Head of the ... - National Health Executive

DNA aptamer finds novel application in regulating cell differentiation – Science Daily

Generating specific cell lineages from induced pluripotent stem cells and embryonic stem cells is the holy grail of regenerative medicine. Guiding iPSCs toward a target cell line has garnered much attention, but the process remains challenging. Now, researchers from Japan have discovered that an anti-nucleolin DNA aptamer, iSN04, can determine a cell's lineage during differentiation. By demonstrating the generation of cardiomyocytes from murine pluripotent stem cells, their concept shows promise as a regenerative therapy.

Self-renewal and pluripotency-the capacity to form any cell lineage-are inherent characteristics of induced pluripotent stem cells (iPSCs). Furthermore, they are highly prized in regenerative therapies targeting cardiovascular, neurological, and metabolic diseases as they are immunologically suitable for transplantation back into a donor. Unfortunately, regenerative medicine is not yet feasible outside a laboratory setting as available protocols to generate target cells are complicated and expensive. This raises a pertinent question: Can regulating the fate of stem cells in clinical settings and at scale be made more economical?

A team of researchers from Shinshu University, the National Institute of Advanced Industrial Science and Technology, and the University of Shizuoka in Japan set out to address this question by leveraging nucleic acid aptamers. Aptamers are single-stranded pieces of DNA that bind to target proteins and are able to modulate signaling cascades during cell differentiation when a stem cell commits to a specific functional role or phenotype. They hold promise in regenerative medicine as they are easily modified, can be synthesized economically, and are suitable for long-term storage.

The team, led by Associate Professor Tomohide Takaya from the Department of Agricultural and Life Sciences at Shinshu University, recently discovered that an anti-nucleolin aptamer, myogenetic oligodeoxynucleotide iSN04, induced myocardial differentiation in embryonic stem cells (ESCs). The study was led by Mina Ishioka, a graduate student in Dr. Takaya's laboratory, and published in The International Journal of Molecular Sciences on 21 September 2023.

"We had previously found that iSN04 promoted myogenic precursor cells (myoblasts) to differentiate into skeletal muscle cells and had hypothesized that the aptamer also enhanced differentiation of pluripotent stem cells. We were intrigued by the prospect of using iSN04 to promote iPSC differentiation into cardiomyocytes as this could lead to regenerating heart tissue," says Dr. Takaya, elaborating on the team's motivation to pursue the research.

Using various assays like RNA sequencing, cell staining and imaging, and molecular interaction and pathway analysis, the researchers investigated iSN04's effect on murine ESCs and iPSCs. iSN04 treatment under differentiating conditions inhibited stem cell commitment to the cardiac lineage. However, when these pluripotent stem cells were treated after experiencing differentiating conditions for five days, specific marker genes were upregulated, and the cells committed to forming beating cardiomyocytes.

"Ours is the first report to confirm a DNA aptamer that allows cardiomyocytes to develop from iPSCs," explains Dr. Takaya when asked about the significance of the work. "We uncovered two mechanisms of nucleolin interference with iSN04 at play whereby early treatment inhibits cardiomyogenesis, while treatment at a later stage enhances the generation of cardiac progenitors. First, iSN04 governs the translocation of nucleolin protein between the cytoplasm, plasma membrane, and nucleus. Second, it results in the modulation of the Wnt signaling pathway that governs cell differentiation."

The immunostaining experiments revealed that nucleolin was retained in the nucleoli following iSN04 treatment. Nucleolar nucleolin has a role in chromatin remodeling and gene transcription, and interestingly enough, Wnt pathway genes were differentially expressed in the RNA-seq data following iSN04 suppression. The team postulates that the iSN04-anchored nucleolin alters gene expression and Wnt signaling. Ultimately, terminal cell differentiation commits to the cardiomyocyte lineage.

And how could these findings impact regenerative medicine and patients' lives in the long term? Dr. Takaya provides insights into the broader implications of their work. "We believe there is a strong case to be made for further studies evaluating DNA aptamers in regenerative medicine. Aptamers are cost-effective and open up the possibility of producing specific cells from the patient's stem cells. But it doesn't end there! Since the aptamers can regulate stem cell fate, they can serve as therapeutic agents for many conditions linked to stem cell dysfunction," he concludes.

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DNA aptamer finds novel application in regulating cell differentiation - Science Daily

A comprehensive review of human trophoblast fusion models: recent … – Nature.com

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A comprehensive review of human trophoblast fusion models: recent ... - Nature.com

Cell atlases of the human brain – Science Daily

In two parallel projects, researchers at Karolinska Institutet have been involved in creating the most comprehensive atlases of human brain cells to date. The two studies, which are published in Science, provide clues on different brain diseases and give hope for medical advancements in the future, such as new cancer drugs.

Knowing what cells constitute the healthy brain, where different cell types are located and how the brain develops from the embryo stage is fundamental to the ability to compare and better understand how diseases arise. There are at present advanced atlases of the mouse brain, but not for the human brain. Until now.

A brain-cell census

"We've created the most detailed cell atlases of the adult human brain and of brain development during the first months of pregnancy," says Sten Linnarsson, professor of molecular system biology at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet in Sweden. "You could say that we've taken a kind of brain-cell census."

The first project was led by Kimberly Siletti from Linnarsson's group. It was conducted in close collaboration with Ed Lein at the Allen Institute for Brain Science in Seattle, USA, as part of the international Human Cell Atlas initiative, and based on three donated human brains from adults. The researchers analysed more than three million individual cell nuclei using the technique of RNA sequencing, which reveals each cell's genetic identity. All in all, the researchers studied cells from just over a hundred brain regions and found over 3,000 cell types, some 80 per cent of which were neurons, the remainder being different kinds of glial cells.

"A lot of research has focused on the cerebral cortex, but the greatest diversity of neurons we found in the brainstem," says Professor Linnarsson. "We think that some of these cells control innate behaviours, such as pain reflexes, fear, aggression and sexuality."

Groundwork for medical advances

The researchers could also see that the cells' identity reflects the place in the brain where they first developed in the fetus, which links to the second project. Here, Emelie Braun and Miri Danan-Gotthold from Sten Linnarsson's group collaborated with the Swedish consortium for the Human Developmental Cell Atlas to analyse over a million individual cell nuclei from 27 embryos at different stages of development (between 5 and 14 weeks of fertilisation). The study enabled the researchers to show how the entire brain develops and is organised over time.

Even though the results are examples of molecular biological basic research, the new knowledge generated can also lay the groundwork for medical advances. Professor Linnarsson's research group has used similar methods to examine different kinds of brain tumours, one of which was a glioblastoma -- a cancer with a poor prognosis.

"The tumour cells resemble immature stem cells and it looks like they're trying to form a brain, but in a totally disorganised way," he explains. "What we observed was that these cancer cells activated hundreds of genes that are specific to them, and it might be interesting to dig into whether there is any potential for finding new therapeutic targets."

Freely available brain atlases

The brain atlases will be freely available to researchers around the world so that they can compare the brain diseases they are researching with what a normally developed brain looks like.

The studies are part of a larger package of articles published simultaneously in the scientific journal Science. The study on the adult brain was supported by a grant from the National Institutes of Health, while the embryo study was financed by the Knut and Alice Wallenberg and Erling-Persson foundations.

Sten Linnarsson is a scientific advisor at Moleculent, Combigene and Oslo University Center of Excellence in Immunotherapy. He and co-authors Alejandro Mossi Albiach and Lars E. Borm also hold shares in EEL Transcriptomics AB, which owns the intellectual property rights to the EEL method ("Spatial RNA localization"). Co-authors aneta Andrusivov and Joakim Lundeberg are scientific consultants for 10x Genomics, which holds the intellectual property rights to the Spatial Transcriptomics (Visium) technique.

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Cell atlases of the human brain - Science Daily

World Arthritis Day sheds light on innovative treatments – Omnia Health Insights

In the UAE, arthritis affects one in five people and is the top cause of disability globally. Arthritis includes over 100 autoimmune and rheumatic musculoskeletal conditions, and while it is commonly associated with ageing, younger patients are also affected.

World Arthritis Day, held on October 12 annually, emphasises the importance of recognising the symptoms of this painful disease, which can help lead to early intervention. Renowned organisations such as the Middle East Arthritis Foundation (MEAF) host focused events to further raise awareness and assist those who suffer from this debilitating disease.

While traditional treatments such as medications, physiotherapy, and surgery can alleviate symptoms, as World Arthritis Day is observed, we examine some alternatives and advancements that may offer hope for an enhanced quality of life.

Related:Understanding Systemic Juvenile Idiopathic Arthritis and gut health

The use of remote monitoring offers a promising way to decrease hospital visits for arthritic patients through a combination of self-management and telemedicine. With the potential to replace labour-intensive outpatient clinic visits, this could positively impact healthcare utilisation while keeping disease activity low.

Regenerative medicine in arthritis could utilise cell therapy, bioengineering and gene therapy to stimulate the body's natural healing response. A key development is Platelet-Rich Plasma (PRP), derived from a patient's blood, PRP can be used to treat pain, damaged tendons, hair loss and ageing skin. While it can relieve symptoms and boost healing, its effectiveness may vary based on preparation methods and patient factors.

Similar to fat-based PRP, Autologous Micro-fragmented Adipose Tissue (AMAT) involves liposuction to extract fat, which is then injected into areas needing treatment. Studies show improvements in osteoarthritis pain and function, but consistency in AMAT quality remains a challenge.

Stem cell therapy holds great potential for tissue repair and regeneration. The various stem cell types include: embryonic, adult, induced pluripotent, and very small embryonic-like stem cells. Clinical trials are ongoing and the FDA cautions against unproven therapies from for-profit clinics. It emphasises the need for standardised guidelines and further research to discover the full potential of stem cells in arthritis care.

Related:Gen AI may power the next generation of immunotherapies

Surgical options such as Osteochondral Autograft Transplantation Surgery (OATS) and Matrix-Induced Autologous Chondrocyte Implantation (MACI) use a patient's own or donor tissue to repair localised cartilage damage, preventing arthritis progression. Researchers are exploring gene editing tools like CRISPR-Cas9 to create custom-designed cells and gene therapies that target inflammatory proteins in osteoarthritis.

While these treatments in regenerative medicine demonstrate substantial potential, continuous research, protocol refinement, and establishing standardised methodologies are imperative to fully discover their benefits in the field of arthritis care.

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World Arthritis Day sheds light on innovative treatments - Omnia Health Insights

Adipose stromal cells bioproducts as cell-free therapies … – Journal of Translational Medicine

Cell culture

ASC from lipoaspirates from three donors were processed by the group of Prof. Karen Bieback (University of Heidelberg, Heidelberg, Germany) after informed consent. The Mannheim Ethics Commission II approved the study (vote 2011-215N-MA). The ASC were cultured using MEM- media, Gibco, ThermoFisher Scientific, 2,561,029) and 10% Fetal Bovine Serum (FBS, 10270-106, Gibco, MA, USA) at 37 with 5% CO2 and controlled humidity. These three ASC batches (referred to a N=3 biological replicates in the figure legends) were shipped as cryo-aliquots to the other two centers to be cultured under identical harmonized culture conditions from passage 46 as detailed previously [29]. Bioproducts were derived from the conditioned medium of either 3D cultured ASC, processed by size exclusion chromatography to yield (1) EV-SEC or the (2) protein-rich fraction, or 2D-cultured cells, processed by ultracentrifugation to yield (3) EV-UC or after concentration to yield (4) the conditioned medium (CM) or (5) the respective wash-off (CM-WO) (Fig.1).

At 80% confluence, ASC were passaged and seeded in a hollow-fibber bioreactor at a concentration of 14106 cells/cartridge (20kDa MWCO, 450cm2, C2025D, FiberCell System-KD Bio, France). Prior to injecting the cells, a pre-culture step was carried out to initiate and activate the bioreactor, first Dulbeccos phosphate-buffered saline (PBS) for 24h, followed by fibronectin coating over-night. After the pre-culture process, ASC were seeded in serum-free MEM- in the extra-capillary space, at 37 with 5% CO2 and controlled humidity for 7days without harvesting the supernatant, with continuous monitoring of glucose levels. Serum-containing medium was used as circulating medium, given that EVs and high molecular weight proteins cannot cross the 20 kD MWCO filter fiber and thus do not contaminate the cell-derived EVs harvested from the extra-capillary-space (according to the Hollow Fiber Bioreactor Protocol for Mesenchymal Stem Cells by fibercellsystems.com) ASC were cultured for 4weeks in the bioreactor and during this period, the supernatant was collected daily. Following centrifugation to remove cell debris (5min at 420g), the supernatant was stored at 80 until EV isolation by size exclusion chromatography (see below) was performed. Cells were harvested and counted to calculate the bioproduct per producer cell concentration.

The secretome obtained in vitro, also named conditioned media (CM), was generated from ASC at passage 4 to 6. Upon reaching 80% confluence, cells were washed with PBS and incubated for 24h in serum-free MEM- medium. The supernatant was collected and centrifuged for 5min at 400g to remove cell debris before being placed in centrifugal concentrator units of 3KDa molecular weight cut-off (UFC9003, Merck Millipore, USA). The CM was centrifuged for 90min at 3,000g, 4 using an Eppendorf 5810 R Centrifuge to achieve tenfold concentration. The flow-through resulted from the concentration step (thereafter named wash-off, CM-WO) was kept and used as a control. Concentrated conditioned media samples were stored at 80 until further use. Cells were harvested and counted to calculate the bioproduct per producer cell concentration.

When the cells reached 80% confluence, they were starved for 1624h in serum-free medium. The supernatant was collected and centrifuged for 20min at 3000g to remove cell debris and apoptotic cells. The supernatant was then ultracentrifuged for 2h at 100,000g, 4 using Beckman Coulter Optima L-100K Ultracentrifuge (Beckman Coulter, CA, USA) with the rotor type 70Ti. The EV pellet was resuspended in PBS supplemented with 1% DMSO. The suspension of EVs (EV-UC) was then stored at80 until further use. EVs were collected from ASC at 4-6th passage. Cells were harvested and counted to calculate the cell equivalents used for cell treatments.

After thawing at 4, samples were centrifuged for 10min at 300g and 20min at 4000g. After, the supernatant was filtered through a 0.2m syringe filter and concentrated with a 100kD MWCO concentration filter to a final volume of 10mL. The qEV10-IZON column 35mm was initially washed with sterile PBS, and then 10mL of the sample was added to concentrate it to the final volume of 1.5mL (Vivaspin 20, 100,000 MWCO PE, Sartorius). Each EV sample (EV-SEC) and the resultant supernatant containing the protein fraction (Protein-Rich Fraction) were collected, concentrated (Vivaspin 20, 100,000 MWCO PE, Sartorius) and stored at 80 until further use.

ASC derived bioproducts were used at a ratio of 2:1 and 20:1 relative to recipient cells. To do so, we counted the number of ASC after harvesting and used it to relate the number of particles/volumes generated of EVs and CM respectively for each bioproduct.

After the isolation, the concentration of all the samples was measured (a) by Nanosight NS300 or (b) ZetaView.

After the isolation, the concentration of all the samples was measured (a) by Nanosight NS300 (Malvern Instruments Ltd., Malvern, UK) equipped with a 488nm laser module that utilizes Brownian motion and refraction index. The particle size scatters 10nm to 1000nm, although the optimized size range is 70300nm. It uses the scattered light to detect a particle and tracks its motion as a function of time. The particles scattered light was recorded with a light-sensitive camera under a 90 angle to the irradiation plane. This angle allows the Brownian motion of the EVs. Samples were diluted 1:100 in physiologic solution. For each sample, 3 videos of 60s at camera level 15 and threshold 5 were captured using a syringe pump 30. All the samples were characterized with NTA 3.2.16 Analytical software. The NTA settings were kept constant between samples.

After the isolation, the concentration of all the samples was measured b) by ZetaView (Particle Metrix GmbH, Germany). 1L of concentrated EVs was diluted in sterile-filtered PBS in a dilution 1:1,000 and visualized using the ZetaView (sensitivity 80%, shutter 100, 11 positions, 2 cycles; Particle Metrix, Germany).

Super-resolution microscopy pictures of EVs were obtained using a temperature-controlled Nanoimager S Mark II microscope from ONI (Oxford Nanoimaging, Oxford, UK) equipped with a 100 , 1.4NA oil immersion objective, an XYZ closed-loop piezo 736 stage, and 405nm/150mW, 473nm/1W, 560nm/1W, 640nm/1W lasers and triple emission channels split at 640/and 555nm. For sample preparation, we followed the manufacturers protocol using EV profiler Kit ONI (Alfatest, Rome, Italy). Before each imaging session, bead slide calibration was performed for aligning the channels, to achieve a channel mapping precision smaller than 12nm. Images were taken in dSTORM mode using 50% laser power for the 647nm channel, 30% laser power for the 488nm laser channel, and 30% for the 555 channel. Three-channels (2000 frames per channel) (647, 555 and 488) were acquired sequentially at 30Hz (Hertz) in total reflection fluorescence (TIRF) mode. Single-molecule data was filtered using NimOSsoftware (v.1.18.3, ONI) based on the point spread function shape, photon count and localization precision to minimize background noise and remove low-precision and non-specific colocalization. Data has been processed with the Collaborative Discovery (CODI) online analysis platform https://www.alto.codi.bio/ from ONI and the drift correction pipeline version 0.2.3 was used. Clustering analysis was performed on localizations and BD clustering-constrained parameters were defined (photon count 300-max, sigma 0200nm, p-value 01, localization precision 020nm). Colocalization was defined by a minimum number of localizations for each fluorophore/protein within a distance of 100nm or a distance used from the centroid position of a cluster.

MACSPlex Exosome Kit (Miltenyi Biotec, Bergisch Gladbach, Germany) containing fluorescent labeled (FITC-PE) capture beads coupled to 37 exosomal surface epitopes and 2 isotope controls was used, following the manufacturers instructions (in detail: CD3, CD4, CD19, CD8, HLA-DR, CD56, CD105, CD2, CD1c, CD25, CD49e, ROR1, CD209, CD9, SSEA-4, HLA-ABC, CD63, CD40, CD62P, CD11c, CD81, MCSP, CD146, CD41b, CD42a, CD24, CD86, CD44, CD326, CD133-1, CD29, CD69, CD142, CD45, CD31, REA control, CD20, CD14, mIgG1 control). Briefly, 15L of beads were added to 120L of buffer or sample, including a total of 1109 EVs, and the complex was then incubated on a rotor overnight at 4. After the incubation and washing steps, a cocktail of APC fluorescent antibodies against tetraspanins (CD9, CD63 and CD81) was added (allowing the detection of beads bound EVs) and set on the rotor for 1h at room temperature. After washing, samples were detected using BD FACSCelestaTM Flow Cytometer (BD Bioscience, NJ, USA). Median background values of buffer control were subtracted, and samples were normalized to the median fluorescence intensity of tetraspanins.

Proteins extracted from Hela cells were used as cellular control, the pellet was resuspended in RIPA buffer (50mM TrisHCl, pH7.4, 150mM NaCl, 1% Triton X-100, 1% Na-deoxycholate, 0.1% SDS, 0.1mM CaCl2, and 0.01mM MgCl2 supplemented with protease inhibitor cocktail (Thermo Fisher Scientific), incubate 30min in ice vortexing every 10min and centrifuge 20min at 20,000g. An equal volume of bioproducts (38L) was loaded and separated on 415% Mini-PROTEAN TGX Precast Gels (Bio-Rad, USA). Bioproducts and cell lysates were treated with protein loading dye (Laemmli sample buffer; Bio-Rad) with freshly added -mercaptoethanol 10%; v/v; Sigma, Germany) and boiled for 5min at 95 before SDS-PAGE. Proteins were subsequently blotted to a nitrocellulose blotting membrane (0.2m; 1,060,000; GE Healthcare, USA). Membranes were blocked in 5% BSA (Carl Roth, Germany) in 0.1% Tween in TBS (TBS-T). After blocking, blots were probed with the following primary antibodies diluted in 5% BSA/TBS-T: Calnexin (1:500 dilution, E-10, Santa Cruz Biotechnology). After overnight incubation at 4, membranes were washed 3 times with TBS-T and subsequently incubated with the secondary antibody dilution: Polyclonal Goat anti-mouse HRP (1:5000 dilution; P0447) for 1h at room temperature followed by washing. Blots were then developed using Western Bright ECL (541,004; Biozym Scientific, Germany) and protein bands were detected using the FusionCapt Advanced Solo 4 (Vilber, Germany).

The capacity of ASC or their bioproducts to inhibit induced proliferation of peripheral blood mononuclear cells (PBMCs) was analyzed as described before [27]. PBMCs were isolated from leukapheresis samples from healthy donors, provided by the German Red Cross Blood Donor Service in Mannheim (Mannheim Ethics Commission; vote number 2018-594N-MA). To assess their proliferation, PBMCs were labelled with proliferation dye Cytotell Green (ATT Bioquest, 22,253) (1:500 dilution) and seeded at a 1:10 ASC/bioproduction:PBMCs ratio in RPMI, supplemented with 10% FBS, 2% l-glutamine (PAN Biotech, P04-80100), 1% Penicillin/Streptomycin (PAN Biotech, P06-07100), and 200U/mL IL-2 (Promokine, C61240). PBMC proliferation was stimulated with phytohemagglutinin-L (PHA, 4.8g/mL (Biochrom, Merck Millipore, M5030)). PBMCs cultured alone without ASC in the absence and presence of PHA served as negative and positive controls, respectively. After 5days, PBMC proliferation was measured based on the dilution of Cytotell Green dye using a FACS Canto II (BD Biosciences) and the data were analyzed with FlowJo Software.

THP-1 monocyte-like cell line (ATCC, Manassas, VA, USA) were cultured in RPMI-1640 growth medium with l-Glutamine (Sigma-Aldrich Ireland Ltd. Wicklow, Ireland) supplemented with 10% FBS (Sigma-Aldrich), 1% penicillin G (100U/mL) and streptomycin (100g/mL) solution (Sigma-Aldrich). In vitro assessment of phagocytic activity was done as described before [30]. THP-1 cells were seeded at a density of 5104 cells/well in dark 96 well-plates (Perkin Elmer Ireland Ltd. Dublin, Ireland) and exposed to 1g/mL of para-methoxyamphetamine (PMA, Sigma-Aldrich, St. Louis, MO, USA) for 48h to induce a macrophage-like phenotype. Cultures were washed with DPBS and fed with growth media for 24h. Afterwards, cells were activated with 100ng/mL of lipopolysaccharide (LPS, Sigma-Aldrich) for 24h. To measure the phagocytic capacity, Zymosan A FITC BioParticles (Thermo Fisher Ltd.) were used. Particles were opsonized with human serum (2mg/mL per 2107 particles, Sigma-Aldrich) for 1h and added to the cells in experimental media containing ASC bioproducts and growth media for 4h. Then, cells were washed twice with DPBS, fixed with 4% PFA for 15min and stained with Hoechst 33,342 (Invitrogen, Thermo Fisher Ltd). Images were taken on the Cytation 1 Imaging Reader at 20X (BioTek, with Gen5 Version 3.04 software, Swindon, UK). Six replicates were undertaken per condition and particle analysis was done by counting particle opsonization in a minimum of 200 cells per well.

HUVEC were seeded in 48-well plates at 84,000 cells/cm2 and cultured overnight. Subsequently, a p200 tip was used to create a scratch in each monolayer. Cultures were washed with DPBS before adding EVs/CM as described before. Complete EndoGRO-LS medium was used as a positive control, while EndoGRO-LS without FBS and VEGF served as a negative control. Scratches were imaged immediately after the addition of CM (0h) and after 8- and 24-h incubation using the automated Cytation 1 Imaging Reader at 4X. Six replicates were undertaken, and the total area of each scratch was measured using Image J. The percentage of closure was calculated relative to time 0h.

20,000 ASC were seeded in a 96-well Essen ImageLock plate and cultured overnight. Then, a 96-pin WoundMaker was used to create precise and reproducible wounds in all the wells. After the wound, the cells were washed 2 times with DPBS and ASC bioproducts added in different concentrations. Plates were then cultured in an IncuCyte ZOOM incubator and every 3h were taken a picture with the software. The results were analyzed after 24h. Relative Wound Density algorithm was used to report data.

Human umbilical vascular endothelial cells (HUVEC) either from Lonza or prepared as described before [31] and cultured until the 6th passage in EndoGRO-LS Complete Culture Media Kit (SCME001, Sigma-Aldrich, St. Louis, MO, USA). In vitro formation of capillary-like structures was performed on growth factorreduced Matrigel (356,231, Corning, NY, USA, center 1 and 3) or geltrex (Geltrex LDEV-free reduced growth factor matrix; Thermo Fisher Scientific, United States, center 2) HUVEC cells were treated with EVs or CM as described before, seeded at a density of 10103cells/well on a 48-well plate. Positive control was full EndoGro-LS medium, negative control medium without VEGF and FBS (as used for all the conditions). Cells were periodically observed with a Nikon TE2000E inverted microscope (Nikon, Tokyo, Japan), and experimental results were recorded after 16h; 3 images were taken per well. Image analysis was performed with the ImageJ software v.1.53c, using the Angiogenesis Analyzer (center 1,3). The data from three independent experiments were expressed as the meanSD of tube length in arbitrary units per field. Center 2 used live cell imaging (Incucyte Zoom) to assess network formation as described before [32].

Presence of vascular endothelial growth factor (VEGF) on ASC bioproducts was determined by solid phase sandwich ELISA using the human VEGF DuoSet ELISA (R&D Systems, USA) according to manufacturers instructions. The samples were read immediately at 450nm with a wavelength correction at 570nm using a VICTOR X4 multilabel plate reader (Perkin Elmer, Waltham, Massachusetts, USA). Levels of cytokines were quantified against an eight-point standard curve using twofold serial dilutions in reagent diluent.

The Pierce BCA Protein Assay Kit (ThermoFisher Scientific, UK) was used to determine protein concentration. In order to quantify the total amount of protein, samples were first lysed with RIPA buffer 4:1 (ThermoFisher Scientific, UK) for 30min on ice. The assay was carried out as per manufacturers instructions. The absorbance values were read in a VICTOR X4 plate reader (Perkin Elmer) at a 550nm wavelength, and the protein concentrations of the samples were quantified against the standard curve.

Statistical analysis was performed using GraphPad prism v9.4.2 (GraphPad software, USA). Data are expressed as meanstandard deviation (SD). N indicates biological replicates; n indicates technical replicates. Statistical differences among groups were calculated using ordinary two-way analysis of variance (ANOVA) and Tukeys post-hoc test when group distributions were normal (ShapiroWilks test) and variances of populations were equal (Bartletts test). When either or both assumptions were violated, non-parametric analysis was conducted; KruskalWallis test used to perform multiple comparison analysis and Dunns multiple comparison test for pairwise comparison. Results were considered statistically significant when p>0.05.

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Adipose stromal cells bioproducts as cell-free therapies ... - Journal of Translational Medicine

SIRT2 Works Against Cardiac Aging in Mice and Monkeys – Lifespan.io News

Working with non-human primates, scientists have discovered that the protein SIRT2, a member of the sirtuin family, might play an important role in slowing cardiac aging [1].

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The heart is arguably the hardest worker among the organs, constantly pumping enormous amounts of blood without ever skipping a beat (well, almost). This marvel of evolution works for decades before it begins to show its age. Heart aging happens due to all the usual culprits, including chronic inflammation, mitochondrial dysfunction, oxidative stress, and telomere damage [2].

In this study published in Nature Aging, the researchers used long-tailed macaques to elucidate the molecular aspects of cardiac aging using multi-omics analysis. Unlike short-lived mice and rats, non-human primates like these have hearts that closely resemble those of humans and, due to their relatively long lifespan, suffer from spontaneous heart conditions as well.

The researchers compared the hearts of eight young (4-6 years) and eight aged (18-21 years) monkeys, which roughly translates to 16 and 65 human years. In aged monkeys, hearts exhibited all the familiar signs of aging: they contained more senescent cells and more fibrotic areas, and their heart muscle cells were significantly enlarged with structural abnormalities. The levels of several inflammatory factors were elevated as well.

Using proteomic analysis, the researchers identified 126 upregulated and 43 downregulated aging-associated differentially expressed proteins (DEPs).Further analysis showed that the upregulated DEPs were mainly related toinflammation, blood clotting, and fibrosis, while protein synthesis, mitochondrial function, and lipid metabolism DEPs were downregulated.

The researchers then compared those DEPs to genes known to be involved in age-related cardiovascular diseases. SIRT2, a SIRT family protein that often pops up in studies of aging [3],was the only protein that was downregulated in aged monkey hearts and was also linked to all four types of cardiovascular diseases. It was also the only downregulated DEP that overlapped with the aging-related genes from the Aging Atlas database.

The scientists then generated human SIRT2-deficient cardiomyocytes from embryonic stem cells. The resulting cells resembled old cardiomyocytes, including hypertrophy and an increased percentage of senescent cells. They also showed signs of mitochondrial dysfunction.

Transcriptomic analysis showed that many genes were either upregulated or downregulated in SIRT2-deficient cardiomyocytes compared to young healthy cells. The researchers were able to identify the transcription factor (a gene that regulates expression of other genes) STAT3 as a major driver of those changes. STAT3 is also a well-known mediator of inflammation.

Notably, STAT3 was the only transcription factor that controlled changes in gene expression in both SIRT2-deficient human cardiomyocytes and in aged hearts of monkeys of both sexes. The researchers then confirmed via a technique called co-immunoprecipitation that STAT3 was one of the few transcription factors to interact with SIRT2.

SIRT2 acts by deacetylating proteins (removing an acetyl group from lysine residues, which alters the proteins function). Overexpression of SIRT2 led to decreased levels of acetylated STAT3, suggesting that SIRT2 recognizes STAT3 as a substrate. STAT3 levels did not react to overexpression of a SIRT2 mutant that lacked deacetylation ability. Aged monkey hearts had more acetylated STAT3 than young ones, showing impaired deacetylation.

Since transcription factors act by changing the expression of other genes, the researchers searched for downstream targets that would be relevant to the cardiac aging phenotype. They identified the gene CDKN2B, which encodes the senescence-related protein p15, as an important target. Apparently, acetylated STAT3 induces the transcription of CDKN2B, which, in turn, induces cellular senescence in cardiomyocytes. By deacetylating STAT3, SIRT2 intervenes in this process and ameliorates cardiac aging.

The researchers tested this hypothesis by injecting the hearts of aged mice with viral vectors containing SIRT2. Decreased ejection fraction and fractional shortening, two major markers of cardiac aging observed in old mice, were partially reversed by the treatment, as was the age-related enlargement of cardiomyocytes, indicating a possible cardioprotective role for SIRT2.

In this study, we systemically surveyed the multi-dimensional profiles of the NHP heart and unveiled a panel of critical biological pathways that shifted during primate heart aging. We identified SIRT2 as a key mediator of geroprotection in primate heart aging and showed that SIRT2-deficient human cardiomyocytes recaptured key senescence features of aged primate hearts. We also found that SIRT2 formed complexes with STAT3 and deacetylated it on Lys685, which, in turn, transcriptionally inactivated the senescence inducer CDKN2B. Thus, our results suggest a SIRT2STAT3CDKN2B axis, regardless of sex, in the regulation of primate cardiomyocyte senescence.

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[1] Ye, Y., Yang, K., Liu, H., Yu, Y., Song, M., Huang, D., & Liu, G. H. (2023). SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B. Nature Aging, 1-19.

[2] Li, H., Hastings, M. H., Rhee, J., Trager, L. E., Roh, J. D., & Rosenzweig, A. (2020). Targeting age-related pathways in heart failure. Circulation research, 126(4), 533-551.

[3] de Oliveira, R. M., Sarkander, J., Kazantsev, A. G., & Outeiro, T. F. (2012). SIRT2 as a therapeutic target for age-related disorders. Frontiers in pharmacology, 3, 82.

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SIRT2 Works Against Cardiac Aging in Mice and Monkeys - Lifespan.io News

Bayer Opens First Cell Therapy Manufacturing Facility to Advance … – BioSpace

BERLIN, Germany & BERKELEY, Calif.--(BUSINESS WIRE)-- Bayer AG announced today the opening of its first Cell Therapy Launch Facility in Berkeley, California to create the capacity to bring cell therapies to patients on a global scale. The $250 million (USD), 100,000-square-foot facility will supply the material required for late-stage clinical trials and potential commercial launch of BlueRock Therapeutics bemdaneprocel (BRT-DA01), an investigational cell therapy currently in evaluation for treating Parkinsons disease. In addition, it includes space for a second module of production suites to support additional cell therapies as Bayers portfolio advances. BlueRock Therapeutics LP is a clinical stage, cell therapy company and wholly owned, independently operated subsidiary of Bayer AG.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20231009274687/en/

(Photo: Business Wire)

Cell therapy represent a groundbreaking class of medicines and is an area where Bayer is making a significant investment to research potentially transformative treatment approaches for people with unmet medical needs, said Sebastian Guth, President of Bayer U.S.A. and Pharmaceuticals North America, and member of the Pharmaceutical Executive Committee. Our new cell therapy facility represents true innovation in product development and manufacturing in addition to contributing to Bayers sustainability goal as our first fully electric pharmaceutical manufacturing plant.

The new Cell Therapy Launch Facility is part of a transformation at the companys dedicated biotechnology site in Berkeley, where Bayer has invested nearly USD 500 million in infrastructure over the past five years.

Our teams are driving innovation in late-stage development and manufacturing with a goal of bringing transformational cell and gene therapies to patients on a global scale, and this facility will enable us to make it real, said Jens Vogel, Sr. Vice President and Global Head of Biotech for Bayers Pharmaceutical Division. Bayer is collaborating with biotech innovators, academia, and equipment and automation suppliers to establish platforms that would help bring more therapies to patients faster.

Bayers global biotech organization recognizes the importance of helping innovators transfer their product candidates from the laboratory bench to the clinical study and commercial launch settings. The Biotech team provides its biologic development and manufacturing capabilities for Bayers larger biotherapeutics portfolio, including commercial products and late-stage protein and cell therapies in development. As part of Bayers larger mission of Health for All, the company is now also helping early-stage U.S. and European companies to enable patient trials and commercial launches through its BioPartnering Solutions offerings.

Having access to this Cell Therapy Launch Facility is central to our goal to deliver impactful cell therapies from our pipeline to patients in need, said Seth Ettenberg, President & CEO of BlueRock Therapeutics. Our team is excited to be working shoulder to shoulder with Bayers biotech scientists and manufacturing experts as we look to scale up manufacturing for our first investigational therapy, bemdaneprocel for Parkinsons disease, as it advances through clinical trials.

The new Cell Therapy Launch Facility, launched in conjunction with manufacturing day in the United States, is among several recent investments to advance Bayers biologic pipeline of protein therapeutics, cell and gene therapies including a new Cell Culture Technology Center and Cell Therapy Labs. The new Cell Therapy Launch Facility features flexible, modular space for cell culture, viral transduction and automated filling of cell therapies leveraging Biotech@Bayer expertise in iPSC and CAR-T characterization, process development, analytics and clinical to commercial production.

Beyond Berkeley, the companys global biotech network includes biologic development, manufacturing science, industrialization and advanced manufacturing engineering teams in Wuppertal and Leverkusen, Germany; and Basel, Switzerland; with a full complement of labs and clinical production suites.

About bemdaneprocel and Parkinsons Disease

Bemdaneprocel (BRT-DA01) is an investigational cell therapy designed to replace the dopamine producing neurons that are lost in Parkinsons disease. These dopaminergic neuron precursors are derived from pluripotent stem cells (PSC) that are human embryonic stem cells. In a surgical procedure, these neuron precursors are implanted into the brain of a person with Parkinsons disease. When transplanted, they have the potential to reform neural networks that have been severely affected by Parkinsons and restore motor and non-motor function to patients. Planning is underway for BlueRock Therapeutics Phase II study that is expected to begin enrolling participants in H1 (first half) 2024.

Parkinsons disease is a progressive neurodegenerative disorder caused by the death of nerve cells in the brain, leading to decreased dopamine levels. At diagnosis, it is estimated that patients have already lost 50-80% of their dopaminergic neurons. The loss of these neurons leads to a progressive loss of motor function and symptoms such as tremors, muscle rigidity, and slowness of movement. Even with medication, the symptoms of Parkinsons disease can fluctuate during the course of the day. According to the Parkinsons Foundation, more than 10 million people worldwide suffer from Parkinsons disease, with approximately one million living in the United States. There is no cure, and the effectiveness of current treatments decreases over time.

About BioPartnering Solutions for Biotech Innovators in U.S. and Europe

Through Bayers BioPartnering Solutions, innovators can leverage industry-leading biotech process development and biomanufacturing capabilities to make their therapeutic candidates a reality. Bayers highly skilled Biotech teams and infrastructure which includes preclinical, clinical and commercial launch scale manufacturing are available to advance promising cell therapy, monoclonal antibody and protein therapeutic candidates from the discovery bench to patients. Through BioPartnering Solutions, Bayer provides early-stage companies with a single source of IND- and BLA-enabling development; bioprocess and biochemical engineering; clinical and commercial manufacturing. A range of complementing support service functions such as supply chain management, procurement, quality, and CMC strategy support for regulatory filings are also available. For more information visit: https://www.bayer.com/en/us/BioPartneringSolutions.

About Bayers Biotech Campus in Berkeley, CA

Innovation happens in communities which foster it. Bayer has a 46-acre site located in Berkeley, CA where a team of about 1,000 employees drives the development and manufacturing of traditional protein therapeutics as well as novel cell and gene therapies. It has also served as the global commercial supply center for manufacturing and supplying Bayers biotherapeutics for people living with hemophilia A around the world for 30 years.

During todays event, Bayer celebrated its continuing relationship with the City of Berkeley through a 30-year extension of its Development Agreement which will support up to one million square feet of additional infrastructure. Through the agreement, Bayer will invest more than $30 million in the local community in career technical education; initiatives focused on health equity, economic resiliency and climate action; and more. For more information visit: https://www.bayer.com/en/us/berkeley-site-updates.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to http://www.bayer.com.

Find more information at https://pharma.bayer.com Follow us on Facebook: http://www.facebook.com/bayer Follow us on Twitter: @BayerPharma

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayers public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

View source version on businesswire.com: https://www.businesswire.com/news/home/20231009274687/en/

Bayer U.S.-based Media Contacts: Cathy Keck, +1-206-249-5191 Email: cathy.keck@bayer.com

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Bayer Opens First Cell Therapy Manufacturing Facility to Advance ... - BioSpace

Stem Cell Treatment Discussed with Cerebral Palsy Community – Mirage News

Exploring the boundaries of stem cell therapy, scientists consulted the cerebral palsy community to understand their perspectives.

Dr Courtney McDonald and Dr Madeleine Smith, in collaboration with researchers at the Cerebral Palsy Alliance, surveyed people in the Australian cerebral palsy community to better understand the acceptability of NSC treatment.

They distributed an online survey and received responses from 232 Australians with cerebral palsy, their parents and/or carers.

Cerebral palsy is the most common physical disability of childhood and currently has no known cure. Researchers at Hudson Institute of Medical Research have been investigating neural stem cell (NSC) treatment for cerebral palsy, but not without considering important ethical and practical considerations for the use of NSCs.

Various stem cell therapies are currently being explored for the treatment of cerebral palsy, including some in clinical trials. Advancing stem cell research is a priority for the cerebral palsy community and neural stem cells offer potential as a future regenerative treatment.

The researcher's rationale was that it's much better to engage with the community early in their research, rather than down the track, during clinical implementation.

"NSC treatment for cerebral palsy is complex, and researchers need to consider the therapeutic source of NSCs and how they are administered as a treatment.," Dr Smith said. "For instance, NSCs need to be administered directly into the brain via neurosurgery in order to replaced damaged brain cells. Another significant factor is that they can be obtained from both adult donors as well as embryonic and fetal sources."

This procedure also needs to be accompanied by strong drugs, called immunosuppressants, that help to ensure the NSCs stay in the brain and are not rejected by the body. However, both the invasiveness of neurosurgery and the use of these drugs present treatment risks.

"Via a research survey, we wanted to better understand, given all the complexities, if NSC treatment for cerebral palsy is an acceptable treatment." Dr Smith said.

Natasha Garrity, Research Assistant at Cerebral Palsy Alliance Research Institute and Co-Chair of the CPA Stem Cell Reference Group, welcomed this research as an important opportunity for people living with cerebral palsy and their families to provide their perspectives.

"It is critically important to respect the lived experience of the people with CP receiving this potential treatment and the views of their support network. By involving consumer stakeholders early on in the research process, the treatment can both be better understood by the community and targeted to the groups that are willing to use the treatment option," she said.

"Cerebral Palsy Alliance is committed to and passionate about involving people with a disability and their families in research for the benefit of researchers, clinicians and the CP community."

"Overall, the survey results showed that NSC therapy is deemed acceptable in the community," Dr Smith said. "even with the known complexities of neurosurgery and the need to use immune suppressing drugs."

"The survey also provided important insights into community expectations of NSC treatment there was some hesitancy reported, which is to be expected and we can learn from the various opinions in the community to inform our future research."

Some of the responses from survey participants are listed below:

"If my brother can help himself get ready or be able to transport himself even a little bit without assistance from the family, that would be great."

"I'd love to be able to have better days than worse days. To wake up with no pain."

"It would mean inclusion. And validation to her that she is a valuable asset. Currently she is spoken over, ignored, or spoken down to."

(Anonymous participant quotes)

The findings from this study informs the work that scientists are conducting in the lab so that new treatments are acceptable to the cerebral palsy community. Additionally, this study is a great example of how early collaboration could aid in moving towards timely treatments for the people that need it the most.

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Stem Cell Treatment Discussed with Cerebral Palsy Community - Mirage News

SightCare Reviews – Legit Ingredients or Negative Scam Complaints … – Seattle Weekly

Everyone wishes to have optimal eye health because without it the world can turn bleak. People cannot function or do everyday tasks that seemed so easy once in their lives. Maybe, that is why so many people are supplementing their diet with vision supplements.

One such supplement is Sight Care. The blend of natural ingredients with no side effects is a popular choice in the United States. The official website of Sight Care says that they have helped thousands of people restore their vision naturally.

But is it really as effective as the makers claim? The official website says that you will not need any surgery or feel the need to wear glasses. They even go on to say that it can reverse blindness! That is really shocking and if true, miraculous! To get to the truth, we did exhaustive research.

In this Sight Care review, you will discover everything about the dietary supplement. We will tell you everything we discovered in our research about this vision supplement.

First, lets take a look at the summary:

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Dietary Supplement

Quantity:

Each bottle of SightCare contains 60 capsules

Side Effects:

Customer reviews did not reveal any side effects (See what people are saying!)

Characteristics:

Ingredients:

Bilberry Extract, Eyebright, N-Acetyl-L-Cysteine, Quercetin, L-Lysine, Astaxanthin, Lutein and Zeaxanthin, and others

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Poor eyesight can be caused by several factors. Some of the most common ones are age-related macular degeneration, glaucoma, cataracts, eye infection, etc. Exposure to blue light and hereditary eye conditions can also be the leading causes of poor eye health.

Sight Care supplement was manufactured after Shinya Yamanaka discovered the power of adult repair stem cells. Scientists in the United Kingdom were using stem cell therapy to regenerate eye cells to treat blindness and age-related diseases like cataracts and other eye health problems.

This scientific discovery repaired the retinas of a man in his 80s and a woman in her 60s. Earlier, the test subjects could not even read or see clearly due to poor eye health. But, after the trials, they could read up to 80 words in a minute.

When David and his friend, Mark read this research in the journal they decided to make Sight Care.

The unique feature of SightCare vision health supplement is that despite being a supplement that helps in maintaining healthy vision, it does not stop at eye health benefits only. The vision supplement also promotes your overall well-being.

The health benefits of SightCare vision health formula are innumerable. Well, not literally but they are too many for us to discuss all of them here. You can write books on each ingredients benefits if you wish. That is how many benefits Sight Care supplement has to offer!

SightCare: Try it now, you wont be disappointed!

David Lewis is the creator of the Sight Care eye health supplement. He is an eye specialist and has over 37 years of experience in helping people support healthy eye function.

In his later years, David struggled with blurred and poor eyesight. The cause was age-related macular degeneration. This made David search for a solution along with his friend, Mark. Together they created this blend of natural ingredients to support vision health naturally.

The eye health formula is made in an FDA-approved and GMP-certified facility in the USA. The makers have tested the formula multiple times to ensure that it is clean and effective.

Before you get tempted to buy this supplement to support healthy vision, you should know if it is even made for you. You do not need to make unnecessary purchases and include something in your diet that you do not need.

The official website of the SightCare vision formula claims that anyone between the ages of 19 and 90 can take the supplement. As the ingredients are plant-based, the vision supplement will have no side effects on users.

So, if you are struggling with vision impairment or age-related eye diseases, say age-related macular degeneration, SightCare will be the right choice for you. You are suitable to use it if you want to maintain healthy vision.

SightCare takes a multi-action approach to protect the eyes and promote healthy eye function. Let us give you an overview of how it works in a simple way.

First of all, the SightCare eye supplement works to boost the growth of adult repair stem cells. Adult repair stem cells are free agents which means they have no assigned role. The major function of adult repair stem cells is to assume the role of cells wherever our body or organs require them. In the case of age-related macular degeneration, adult repair stem cells assume the role of eye cells to enhance vision.

Moreover, Sight Care has ingredients with anti-inflammatory properties that induce a healthy inflammatory response to reduce inflammation caused by eye diseases and support healthy vision. The ingredients in the formula protect the eyes from free radicals and blue light to prevent any damage from occurring.

To support healthy eye function and rectify age-related macular degeneration, the Sight Care pills promote blood circulation and keep your blood vessels healthy.

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Sight Care dietary supplement brings multiple health benefits to you. From the official website and Sight Care reviews, we have gleaned the following health benefits of the Sight Care supplement:

The ingredients in the Sight Care eye formula support healthy vision. As supported by the SightCare reviews, the formula supports overall eye health. The blend of natural ingredients nourishes your eyes and prevents free radicals from damaging your eye tissue. Thus, you get healthy eyes.

The vision supplement also has cell regeneration ability to regenerate eye cells and prevent age-related eye diseases like macular degeneration. This helps in regenerating eye tissues to maintain healthy eyes with clear vision.

Sight Care formula supports liver health. SightCare eye formula has n-acetyl which has antioxidant and anti-inflammatory properties. A healthy inflammatory response protects your liver from inflammation damage and reduces the risk of liver diseases. It helps in detoxifying your body and prevents free radical damage to support a healthy liver.

By promoting healthy liver function, Sigh Care optimizes your overall well-being.

Sight Care also helps improve brain health as supported by the official website and SightCare reviews. N-acetyl has anti-inflammatory properties that protect your brain from inflammation and oxidative stress to improve brain health.

Brain Health supports healthy vision and overall eye health.

Sight Cares natural ingredients also enhance vision to support night vision. Now, you do not have to fumble around or squint hard to see things in the dark.

Sight Care is scientifically proven to specifically target age-related macular disease or macular degeneration which is the leading cause of poor eyesight in older people. Thus, it supports your overall eye health despite your age.

Click here to order your supply of SightCare now and start enjoying its benefits!

SightCare is a revolutionary product that combines the power of Bilberry Extract, Eyebright, N-Acetyl-L-Cysteine, Quercetin, Astaxanthin, Lutein, and Zeaxanthin into one powerful formula.

Its designed to help support healthy eyesight and promote clearer vision so you can get the most out of life with the help of powerful natural ingredients:

A study conducted on the effects of bilberry extract on eye health supports its inclusion in SightCare. In a randomized, double-blind, placebo-controlled trial published in the Journal of Science of Food and Agriculture, researchers looked at the impact of bilberry extract supplementation on visual function in 120 participants with early-stage AMD.

The study found that after six months of bilberry extract supplementation, there was a significant improvement in visual acuity, contrast sensitivity, and macular pigment optical density compared to the placebo group.

According to the study, participants who took the bilberry extract supplement experienced a 25% improvement in visual acuity compared to only 9% in the placebo group. Additionally, their contrast sensitivity increased by 33%, while the placebo group only showed a 13% increase.

At a microscopic level, eyebright contains various bioactive compounds such as flavonoids, iridoids, and tannins. These compounds possess antioxidant and anti-inflammatory properties, which play a key role in maintaining and improving eye health.

Another vital mechanism by which eyebright aids in visual acuity and eyesight protection is its ability to promote blood circulation to the ocular region. The tiny capillaries and blood vessels within the eyes deliver the necessary nutrients and oxygen to maintain the optimal functioning of ocular tissues.

By enhancing blood flow, eyebright ensures that these vital nutrients reach the cells of the eyes, including the retinal cells responsible for signaling and visual perception.

A study conducted by Babizhayev et al. (2016) examined the effects of NAC in patients with early cataracts. The study involved 49 individuals who were divided into two groups: one receiving NAC eye drops and the other receiving placebo eye drops.

The researchers measured various indicators of eye health, including visual acuity, glare sensitivity, and lens transparency, before and after the intervention. The results showed that the group receiving NAC eye drops experienced significant improvements in all measured parameters compared to the placebo group.

Visual acuity improved by 35%, glare sensitivity decreased by 27%, and lens transparency increased by 41%.

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Quercetin is a flavonoid compound found in various plant-based foods such as onions, apples, and berries. On a molecular level, quercetin consists of three rings and several hydroxyl groups, which contribute to its antioxidant and anti-inflammatory properties. When it comes to improving visual acuity and protecting eyesight, quercetin plays a crucial role in several core mechanisms.

By inhibiting the production of inflammatory molecules such as cytokines and chemokines, quercetin helps to reduce inflammation in the eyes. This anti-inflammatory action not only alleviates discomfort but also preserves the integrity of ocular tissues and improves visual acuity.

Moreover, quercetin aids in reducing oxidative stress in the eyes. Oxidative stress occurs when there is an imbalance between the production of harmful free radicals and the bodys ability to neutralize them with antioxidants. In the eyes, this oxidative stress can lead to the development of various eye conditions such as cataracts and age-related macular degeneration (AMD).

Astaxanthin is a naturally occurring red pigment that belongs to the carotenoid family. Its chemical composition consists of a central polyene chain with alternating single and double bonds and several end groups called keto and hydroxyl groups. This unique structure gives astaxanthin its powerful antioxidant properties.

When it comes to vision functioning, astaxanthin demonstrates remarkable benefits. It has a strong affinity for the retina and accumulates in the macula, a small area responsible for central vision. Astaxanthin protects the eyes from harmful ultraviolet (UV) radiation and filters out harmful blue light.

It also acts as a potent antioxidant, neutralizing free radicals that can damage the delicate structures of the eye. Furthermore, astaxanthin enhances blood flow to the retina, improving nutrient delivery and oxygenation, which in turn supports optimal vision functioning.

Numerous scientific studies have provided evidence for the effectiveness of lutein and zeaxanthin in supporting eye health and improving night vision. One specific study published in the Journal of the American Medical Association in 2016 examined the effects of these antioxidants on participants with intermediate AMD.

The study found that a combination of lutein and zeaxanthin supplements significantly reduced the progression of AMD and improved visual acuity compared to a placebo group. Specifically, the lutein and zeaxanthin group had a 10% reduction in the risk of progression to advanced AMD, highlighting the powerful protective effects of these antioxidants.

Furthermore, studies have shown that higher levels of lutein and zeaxanthin in the macula are associated with a lower risk of cataracts and improved contrast sensitivity, especially in low-light conditions.

In a study published in the Journal of Optometry in 2017, researchers found that individuals with higher macular pigment optical density (indicating higher levels of lutein and zeaxanthin) had better night vision and were less affected by glare.

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The advantages of purchasing the Sight Care formula are as follows:

The following are the disadvantages of purchasing Sight Care vision health formula:

We compared Sight Care dietary supplement with other eye health supplements to see how it stands apart from them and we were not disappointed. Take a look at the comparison below:

Ocusil is a dietary supplement that supports healthy eyesight. It provides crystal-clear vision and prevents free radicals from damaging your retina.

In terms of pricing, both Ocusil and Sight Care are the same. You can purchase the basic pack for $69 plus shipping charges.

If we talk about the manufacturing of both supplements then like Sight Care, the Ocusil dietary supplement is also made in an FDA-approved and GMP-certified facility ensuring its effectiveness and quality.

However, both supplements have different list ingredients and target different causes of vision loss to help you in maintaining healthy eyesight. You can go through the ingredient list of both supplements and decide which dietary supplement is better in case you are allergic to any ingredient.

Comparing the money-back guarantee, we found that Ocusil offers a 60-day money-back guarantee only. On this parameter, Sight Care is better as it is covered with a 180-day money-back guarantee.

Overall, both Ocusil and Sight Care can help you maintain healthy eyes. You can make your decision after talking to your physician.

Vision20 is another dietary supplement that supports healthy vision. The supplement fights free radicals and promotes night vision.

Comparing the ingredients of both supplements, we found that they are more or less similar. Except for a few ingredients, that is. Also, both Vision20 and Sight Care are manufactured in an FDA-approved and GMP-certified facility.

Coming to the pricing of Vision20, we found that it is cheaper than Sight Care. People living in the United States can purchase Vision20 for $59 only.

Both the supplements are manufactured by doctors. However, Vision20 is manufactured by Zenith Lab whereas, Sight Care does not mention anything like that. This gives Vision20 more credibility if we test their brands.

Another common thing between Vision20 and Sight Care is that both offer a 180-day money-back guarantee which is a great thing but makes it really impossible to choose one brand between the two.

Again, you can select the supplement based on ingredients. But we think Sight Care will be a good choice because it brings multiple health benefits in comparison to Vision20.

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First and foremost, SightCare is designed for anyone between the ages of 19 and 90. If you find yourself struggling with vision impairment, whether due to age-related macular degeneration or other eye-related issues, SightCare might just be your solution. Its specifically formulated to combat various eye health problems, making it a versatile option for a wide range of people.

But what exactly can SightCare help with? The supplement is crafted to address a multitude of eye health issues. If youre battling age-related macular degeneration, glaucoma, cataracts, or even eye infections, SightCare could offer relief. Its a natural, plant-based solution that promotes overall eye health and prevents further damage caused by free radicals and blue light exposure.

Moreover, SightCare doesnt stop at eye health; it promotes your overall well-being. By supporting healthy vision, SightCare indirectly benefits other aspects of your health. For instance, its anti-inflammatory properties protect not only your eyes but also your liver and brain, enhancing your overall vitality.

So, if youre tired of fumbling for glasses or struggling with poor eyesight, SightCare might be your ticket to clear vision. Its natural ingredients, coupled with a 180-day money-back guarantee, offer you a risk-free opportunity to experience the potential benefits.

Getting a healthy vision has become affordable and if you have made up your mind to buy SightCare vision supplement to tackle age-related eye diseases or vision impairment, let us tell you about the pricing structure of the supplement.

You can buy SightCare vision supplement in the following range of bundles from the official website:

Basic Bundle: The basic bundle consists of one bottle of SightCare. You can purchase it for $69.

Popular Bundle: The popular bundle consists of three bottles of Sight Care. It will cost you $177.

Best Value Bundle: The price of this six-bottle bundle is $294.

The Basic bundle will come with a standard shipping charge. So, your total charge will change on this order accordingly. However, for the Popular and Best Value bundles free shipping is available.

Order SightCare today and be glad you did!

The makers will not leave you hanging once you have purchased the Sight Care Formula or have placed an order. You can visit customer support (getSightCare.com) if you have any questions about the order, ingredients, or anything. Their team will be available to guide you and answer all your questions.

This is one of the most frequently asked questions and for all the right reasons. No one wants to make a risky purchase and lose their money over something that will not help them get a crystal clear vision.

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SightCare Reviews - Legit Ingredients or Negative Scam Complaints ... - Seattle Weekly