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Sarah Irvine’s Battle with MS: The Hope of Stem Cell Treatment – BNN Breaking

By adminJanuary 16, 2024Stem Cell Treatment

Sarah Irvines Battle with MS: The Hope of Stem Cell Treatment

On a quiet street in a bustling city, Sarah Irvine lives a life that is far from ordinary. Diagnosed with a progressive form of multiple sclerosis (MS) in 2019, she faces a daily battle against her own body. In the midst of the turmoil, Sarah, like a beacon of resilience, is aspiring to undergo stem cell treatment in London, a decision that could potentially change the course of her life.

Multiple sclerosis is a debilitating condition where the immune system, in an uncharacteristic act of betrayal, turns against the nerve cells in the brain, spinal cord, and optic nerves. This internal assault can lead to severe impairments in mobility and other neurological functions, trapping individuals in a body that refuses to obey.

For Sarah, this is more than just medical jargon. Its her reality. Every day, she wakes up to a world where simple tasks become Herculean challenges and where the uncertainty of the future looms large. Yet, in the face of adversity, she stands undeterred, ready to fight.

In her quest to combat the impact of this disease, Sarah is setting her sights on a treatment that, while often seen as a last resort, holds the promise of potentially slowing down, or even halting, the progression of her MS symptoms. This treatment involves the transplantation of stem cells, tiny powerhouses of regeneration that may hold the key to resetting the immune system and halting its attack on the nervous system.

Sarahs journey is far from easy. The road to potential treatment is fraught with obstacles, each more daunting than the last. But her determination is unwavering. In her struggle, she becomes a symbol of resilience, a testament to the human spirits indomitable will to survive.

As Sarah navigates her path towards potential recovery, her story serves as a reminder of the ongoing struggle faced by individuals living with MS and the relentless search for effective therapies. In the midst of the battle, however, one thing remains clear: the spirit of the human will, as embodied by Sarah, remains unbroken, undeterred, and unstoppable.

A guide to stem cell therapy in Thailand – Thaiger

By adminJanuary 16, 2024Stem Cell Treatment

PHOTO: Stem Cell Therapy at Identity Clinic

You probably have heard about stem cell therapy and its ability to improve your quality of life and feel sceptical about it. While the procedure may sound like something out of science fiction, its actually a promising medical procedure with a wide range of benefits. In fact, it has grown in popularity and shown remarkable effectiveness over the past few years. Thailand has been quick to adapt stem cell therapy and is now leading the charge in Asia.

If youre thinking about getting stem cell therapy in Thailand, you probably have a lot of questions about it. What exactly is it? Is it the appropriate procedure for your condition? Can it really reverse ageing? Where should you head to in Thailand to receive this treatment? To answer some of your questions, we sat down with Dr. Puii and Josh from Identity Clinic Bangkok to get an insight into stem cell therapy in Thailand.

Before we go into details on stem cell therapy in Thailand, lets first talk about the basics.

Stem cell therapy is a newer medical procedure that uses the power of stem cells, which are unspecialized cells that provide new cells for your body as you grow, and replace specialised cells that are damaged or lost. Were born with these cells and they continue to multiply until we reach the age of around 20. After that, though, their numbers and effectiveness start to decline. At around the age of 30 to 35 years old, they take a significant dip in both quality and quantity. This reduction in stem cells is one reason why our bodies start showing signs of ageing.

Stem cells play a crucial role in our health, helping with growth, repair, and even tackling inflammation. Thats why stem cell therapy is a promising medical procedure to treat various medical conditions.

Stem cell therapy provides a wide range of benefits. While it can be used to treat a range of health conditions, stem cell therapy also makes its way into cosmetic treatments and wellness initiatives. Here are some of the main benefits of stem cell therapy that you can get in Identity Clinic Bangkok, Thailand:

Stem cell therapy offers a wide range of benefits for those seeking enhanced well-being.

One of the most popular benefits of stem cell therapy is skin rejuvenation. The therapy facilitates the healing of bruises, cuts, and other skin imperfections. In addition, it can also reduce wrinkles and increase the strength of your dermis the thick layer of living tissue that forms your true skin beneath the epidermis. Stem cell therapy restores the skin deep down to the cellular level, causing your skin to become brighter and tighter. Thus, youll feel refreshed and rejuvenated after each treatment.

In addition to enhancing your immune system, this cutting-edge treatment can also positively impact your sleep quality, which in turn will boost your overall energy levels. Research by DVC Stem reveals that patients undergoing stem cell therapy have reported impressive results, with a notable 75% increase in stamina and a significant 51.40% improvement in energy levels 3 months after treatment.

Stem cell therapy can improve your cognitive function, such as memory and decision-making abilities. Plus, it can make a big difference in how well your nerves send signals to your muscles, which means it can enhance your motor functions.

Youd be amazed to know how much your blood work can benefit from consistent stem cell therapy. Over time, this can also boost the performance of your kidneys and liver, and generally enhance the health of all your organs.

Stem cell therapy in Identity Clinic Bangkok, Thailand can also be used as targeted treatment for specific conditions.

If youve been dealing with knee pain, stem cell therapy may be able to regenerate your knee joints due to arthritis, traumatic ligament injuries, and degenerative conditions.

Stem cell therapy has shown promise in slowing down dementia, such as Alzheimers disease. This is achieved by substituting impaired cells with robust ones, enhancing memory functionality, and regenerating neurons.

Erectile dysfunction, the inability to keep an erection, can be treated with stem cell therapy. With this therapy, the stem cells act as a muscle inside the penis, thereby rejuvenating its tissues and restoring their functionality.

Stem cell therapy is a breakthrough in the treatment of Crohns disease. It has the potential to lessen intestinal inflammation, foster the recovery of the intestinal lining, and enhance your overall life quality.

According to Dr. Puii, another significant benefit of stem cell therapy is helping individuals with pathological conditions like diabetes, hypertension, and heart conditions. Stem cell therapy becomes a continuous treatment option for those seeking to improve and manage their conditions.

Beyond adult treatments, stem cell therapy shows promise in treating chronic diseases in children, such as cerebral palsy, mental disorders, and movement abnormalities. The therapy offers hope for improving conditions that persist into adulthood.

If youve been reading about stem cell therapy, youre probably aware that there are misconceptions surrounding it, causing confusion and fear. One prevalent misconception suggests that stem cell therapy can increase your risk of cancer. There have been no reports of the therapy causing cancer, but to mitigate potential risks, its essential to get this treatment from trusted clinics that use approved stem cells.

Another misconception about stem cells is that they may lead to the growth of extra limbs. Its crucial to clarify that such fantastical claims lack scientific basis. Stem cell therapy, when administered responsibly, adheres to stringent safety standards and does not result in abnormal cell proliferation or limb regeneration.

Its important to remember that while stem cell therapy isnt a universal solution, its not a harmful procedure. Stem cell therapy doesnt reverse ageing or prompt the growth of additional body parts. Instead, its focus is on aiding the bodys natural healing processes and enhancing overall well-being.

There are many medical centres across Thailand offering stem cell therapy, but not all of them are the same. Just like any other healthcare procedure, the most important thing when it comes to stem cell therapy is choosing the right clinic. Be sure to verify that the doctors and staff are well-versed in the procedure and that the clinic is committed to advancing their stem cell therapy technology, This ensures you receive the best possible treatment with a high success rate.

One of the leading clinics offering stem cell therapy in Thailand is Identity Clinic. With top-notch stem cell banks, world-class laboratories, and VIP rooms, the clinic ensures clients receive a royal and unmatched experience. Heres what Identity Clinic offers to their patients:

What sets Identity Clinic apart is its commitment to high-quality stem cells. They use Mesenchymal Stem Cells (MSCs) from the umbilical cord that are carefully screened for health conditions by world-class certified labs and the US FDA. Moreover, these stem cells come with extensive certifications, blood work, and detailed reports. The clinic uses an ID Barcode system to ensure accuracy and traceability. Therefore, clients have full transparency about the stem cells they receive.

Identity Clinic boasts certifications from esteemed global institutions. These include the American Association of Blood Banks (AABB) standards, a recognition highly esteemed by medical organisations worldwide, particularly those in the United States. The clinic also holds the ISO 9001 certification and uses US FDA-approved medical equipment to provide the best and safest procedures for their patients. Furthermore, the clinic has been honoured with the European Society for Quality Research award from Germany, a prestigious recognition given to organisations that demonstrate exceptional quality and ethical practices.

Patients at Identity Clinic enjoy a luxurious and comfortable experience. From the customer service to the interior, the clinic ensures a premium healthcare journey. The staff goes the extra mile to meet all of your needs. Moreover, the treatment rooms are designed to promote both physical comfort and peace of mind as you undergo stem cell therapy.

Identity Clinic takes pride in staying at the forefront of stem cell research and therapy. The dedicated team, led by renowned doctors like Dr. Shin and Dr. Puii, continuously studies and integrates the latest advancements in stem cell treatment.

Stem cell therapy can work wonders in addressing a wide range of medical conditions. And Identity Clinic is dedicated to offering stem cell therapies for all kinds of patients, including those seeking skin rejuvenation. They combine stem cell therapy with state-of-the-art skin treatments like laser procedures and Thermage. This integrated approach not only enhances overall health but also greatly improves skin texture and appearance, adding a youthful glow like never before.

At Identity Clinic, stem cell therapy is not a one-size-fits-all treatment. They offer personalised care plans for various health conditions to make sure that every patient receives positive and sustained effects from their stem cell therapy. To achieve this, they perform a series of preliminary medical evaluations on every new patient prior to beginning their treatment. Among these tests, checking for allergies and carrying out comprehensive assessments for potential underlying medical conditions are essential parts of their preparation protocol.

If youre curious about the potential benefits of stem cell therapy, be sure to contact Identity Clinic for more information. With a focus on quality, certifications, and personalised care plans, the clinic ensures a top-notch experience for every patient.

Clinical applications of stem cell-derived exosomes | Signal Transduction and Targeted Therapy – Nature.com

By adminJanuary 16, 2024Embryonic Stem Cells

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Clinical applications of stem cell-derived exosomes | Signal Transduction and Targeted Therapy - Nature.com

Developing in-vivo chimeric lungs with pluripotent stem cells – Drug Target Review

By adminJanuary 16, 2024Embryonic Stem Cells

Reverse-blastocyst complementation elucidates the conditions required to form lungs in rat-mouse chimeric models.

Researchers from the Nara Institute of Science and Technology (NAIST) have used the reverse-blastocyst complementation (rBC) method to understand the conditions required to form lungs in rat-mouse chimeric models. They also used the tetraploid-based organ complementation (TOC) method to create a rat-derived lung in their mouse model.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of global deaths. The pathogenesis of COPD is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD.1

Lung transplantation is the only viable treatment option, yet finding suitable lung donors is difficult. However, regenerative medicine is advancing the development of lungs from pluripotent stem cells (PSCs) using interspecies animal models. Current expectations for realisation of the promise of PSCs are at the highest they have ever been. However, there are many challenges that need to be addressed in order to bring PSC technology within the grasp of many more patients. Three particular challenges are: tumorigenicity, immunogenicity, and heterogeneity.2

PSCs and embryonic stem cells (ESCs) from one species can be injected into blastocytes, the cluster of diving cells made by a fertilised egg, in a biological technique named blastocyst complementation to create interspecies chimeric animals. This has enabled successful regeneration of the heart, pancreas and kidney in rat-mouse chimeras, but functional lung formation remains to be achieved successfully in vitro due to the complex three-dimensional (3D) structures and multiple cell types needed. This has warranted more research into the viable conditions required to generate PSC-derived organs.

Fibroblast growth factors (FGFs)are polypeptides with various biological activities bothin vivoandin vitro.3 The fibroblast growth factor 10 (Fgf10) and its interaction with the Fgf receptor isoform IIIb (Fgfr2b) in the lungs are essential for lung development. The rBC method in the new study involved injecting mutant ESCs which fail to show lung formation into wild-type (WT) embryos. This allowed for efficient detection of mutant PSCs in the recipient tissue, aiding the determination of the conditions necessary for successful lung formation in the organ-deficient animal.

The team, led by Dr Shunsuke Yuri and Dr Ayako Isotani, discovered that WT ESCs provide uniform contributions across target and non-target organs in the chimeras. This helped to ascertain that a particular number of WT or normal cells are required to overcome the lung development failure in Fgf10-deficient or Fgfr2b-deficient animals.

Having this understanding enabled them to produce rat-derived lungs in the Fgfr2b-deficient mouse embryos with the TOC method, without the requirement of producing a mutant mouse line. Dr Yuri said: Interestingly, we found that the rat epithelial cells conserved intrinsic species-specific timing in the interspecies model, resulting in an underdeveloped lung. Consequently, these lungs remained nonfunctional post-birth.

The studys findings identified the factors required for the successful generation of functional lungs in rat-mouse interspecies chimeras, as well as the issues to overcome. Dr Yuri concluded: We believe that our study makes an important contribution to the literature by presenting a faster and more efficient method of exploring blastocyst complementation.

These novel results can significantly advance the progress toward developingin-vivochimeric lungs for the purpose of transplantation, which could transform the practical application of regenerative medicine.

This study was published in Development.

1 Hogg JC, Timens W. The Pathology of Chronic Obstructive Pulmonary Disease. Annual Review of Pathology: Mechanisms of Disease. 2008 October 27 [2024 January 5]; 4:435-459. Available from: https://doi.org/10.1146/annurev.pathol.4.110807.092145

2 Yamanaka S. Pluripotent Stem Cell-Based Cell Therapy Promise and Challenges. Cell Stem Cell. 2020 October 1 [2024 January 5]; 27(4):523-31. Available from: https://doi.org/10.1016/j.stem.2020.09.014

3 Birnbaum D, Coulier F, Emoto H, Itoh N, Mattei MG, Tagashira S. Structure and Expression of Human Fibroblast Growth Factor-10*. Journal of Biological Chemistry. 1997 September [2024 January 2024]; 272(37):23191-4. Available from: https://doi.org/10.1074/jbc.272.37.23191

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Developing in-vivo chimeric lungs with pluripotent stem cells - Drug Target Review

No, Rep. Steve Scalise Didn’t Vote Against Stem Cell Research From Which He Is Now Benefiting – Yahoo News

By adminJanuary 16, 2024Embryonic Stem Cells

A long-dormant medical controversy was revived last week following an announcement from House Majority Leader Steve Scalise. On January 5, his office released a statement indicating that he was undergoing a stem cell transplant as part of his previously announced treatment for multiple myeloma. Hearkening back to the stem cell controversies of the early 2000s, a number of posts emerged onlineincluding a viral Reddit thread and tweet with 54,000 likes and almost 10,000 retweetsaccusing the congressman of hypocrisy for receiving a treatment that he allegedly fought against.

The treatment Scalise is receiving has no relation to the embryonic stem cell research often opposed by pro-life Americans, however, and the congressman has never voted to restrict research into the form of treatment he is receiving.

Scalise first announced his diagnosis of multiple myelomaa rare blood cancerin late August 2023, telling reporters a month later that his body had responded well to his first round of treatment. The good news is the cancer has dropped dramatically because of the success of the chemotherapy, he said in September. The next step for Scalise, as mentioned above, is an autologous stem cell transplant. [Rep. Scalise] is currently undergoing the transplant process, marking a significant milestone in his battle against cancer, his offices January 5 statement read. Once the procedure is completed, he will be recovering under the supervision of his medical team and will work remotely until returning to Washington next month. Scalise is receiving treatment in his home state of Louisiana.

Because multiple myeloma attacks a patients bone marrowan essential tissue for the bodys production of blood cellsstem cell transplants are often used to help replace marrow damaged by the cancer with new and healthy marrow. In a typical autologous stem cell treatment, the kind which Scalise is receiving, a patients own hematopoietic stem cells are extracted and frozen multiple weeks before treatment. These cells used to be extracted from the bone marrow itself, but today most patients are given a growth factor that allows for stem cells to be taken directly from the blood. The patient is then given intensive chemotherapy, often in a single large dose, before receiving a transfusion of his or her own healthy stem cells. It then takes two to three weeks for the transfused stem cells to restore the functionality of the bone marrow, during which patients can be substantially immunocompromised because of their bodies inability to produce the white blood cells necessary for proper immune function.

Unlike embryonic stem cells, which are harvested from early stage human embryos and can take the form of any cell in the body, the hematopoietic stem cells used in the treatment of multiple myeloma are extracted from a patients own body or from a voluntary donor and can develop into only a limited range of blood cells. These are not the type of stem cells that are in an embryo that can become anything, Dr. Marc Braunstein, a hematology and stem cell transplant expert at NYU Langone Health, told The Dispatch Fact Check. These are slightly differentiated stem cells that are destined to become blood cells, but not anything else.

Traditional stem cell therapies are widely accepted and utilized in modern medical practice, unlike the embryonic stem cell research that reached a point of national controversy in the mid-2000s. We can debate the ethics of using embryonic stem cells, Braunstein said, but I think in this case were not talking about that at all. According to Braunstein, even patients who are practicing Jehovahs Witnessa religious group that typically rejects the use of blood transfusionsare often not opposed to autologous stem cell treatments. For those individuals who may be leery about the use of embryonic stem cells, I dont think they would be as concerned with the use of adult hematopoietic stem cells, Braunstein said.

Furthermore, Scalise has not taken any notable votes against stem cell researchembryonic or non-embryonic. Two notable bills intended to advance embryonic stem cell research, the Stem Cell Research Enhancement Act of 2005 and Stem Cell Research Enhancement Act of 2007, passed both the House and Senate, but both were vetoed by then President George W. Bush. These votes occurred prior to Scalise assuming office in May 2008, however, and very little legislative activity involving embryonic stem cell research has happened since.

In September 2020, Scalise co-signed a letter by Mississippi Sen. Roger Wicker calling for an end to taxpayer funded embryonic stem cell research at the National Institutes of Health, but the letter expressed no opposition to non-embryonic stem cell research or treatment. In fact, Scalise voted in favor of the Stem Cell Therapeutic and Research Reauthorization Act of 2010, Stem Cell Therapeutic and Research Reauthorization Act of 2015, and TRANSPLANT Act of 2021, all of which reauthorized a program intended to support patients in need of stem cell transplants.

Asked by The Dispatch Fact Check whether they believed allegations of hypocrisy were unfair, Scalises office declined to comment further, instead saying that the statement on his treatment spoke for itself.

If you have a claim you would like to see us fact check, please send us an email at factcheck@thedispatch.com. If you would like to suggest a correction to this piece or any other Dispatch article, please email corrections@thedispatch.com.

ROR2 expression predicts human induced pluripotent stem cell differentiation into neural stem/progenitor cells and … – Nature.com

By adminJanuary 8, 2024Induced Pluripotent Stem Cells

Cell culture

Commercially available hiPSC lines were used in this study (Supplementary Table 1). HiPSC lines were obtained from RIKEN Cell Bank (201B7, 253G1, 409B2, HiPS-RIKEN-1A, HiPS-RIKEN-2A, and HiPS-RIKEN-12A), American Type Culture Collection (ATCC-DYR0110 hiPSC and ATCC-HYR01103 hiPSC), JCRB Cell Bank (Tic), and System Biosciences (human mc-iPS). HiPSCs were screened for mycoplasma contamination and hiPSCs used in this study were mycoplasma-free. Undifferentiated hiPSCs were maintained on an iMatrix-511 (Nippi) in StemFit AK02 medium (Ajinomoto). All cells were cultured at 37C in a humidified atmosphere containing 5% CO2 and 95% air.

Differentiation of hiPSCs into NS/PCs was induced, as previously reported, with a few modifications. For adhesive differentiation, hiPSCs were detached through incubation with StemPro Accutase (Thermo Fisher Scientific) containing 10M Y-27632 for 10min and seeded onto 24-well cell culture plates (BD Biosciences) coated with iMatrix at a density of 25,000 cells/cm2 for 23days before NS/PC induction. Confluent hiPSCs were treated with 10M of the ALK inhibitor SB431542 (Stemgent) and 500ng/mL of Noggin (R&D systems) in DMEM/F12 medium containing 20% KSR. The medium was replaced on days 1 and 2. On day 6 of differentiation, SB431542 was withdrawn, and increasing amounts of N2 media (25%, 50%, and 75%) were added to the knockout serum replacement medium every 2days while maintaining 500ng/mL of Noggin. For suspension differentiation, hiPSCs were treated with 10M Y-27632 for 1h at 37C and dissociated with StemPro Accutase (Thermo Fisher Scientific) containing 10M Y-27632 for 10min to generate single-cell suspensions and suspended in B27N2-based medium [DMEM/F12 with 15mM HEPES, 5% B27, and 5% N2 supplements (Life Technologies), 10M SB431542, 2M Dorsomorphin (Fujifilm), and 10ng/mL bFGF (R&D systems)]. The completely dissociated cells were seeded into ultralow attachment 96-well plates (PrimeSurface 96-well, Sumitomo Bakelite) at 9,000 cells/well, centrifuged at 700g for 3min (quick aggregation). The medium was changed daily for up to 10days; for the first 3days, 10M of Y-27632 was added. Total RNA was obtained from 40 wells of neuro spheres per sample. For microarray analysis, hiPSCs were differentiated into NS/PCs using a STEMdiff SMADi Neural Induction Kit (Stem Cell Technologies) according to the manufacturers instructions. Briefly, hiPSCs were maintained on an iMatrix-coated plate in StemFitAK02 media (Ajinomoto) before NS/PC induction. Cells were harvested using Accutase (Thermo Fisher Scientific); 2106 cells were transferred to a Matrigel-coated 6-well plate in STEMdiff Neural Induction Medium+SMADi (Stem Cell Technologies) supplemented with 10M Y-27632. The medium was replenished daily with warmed (37C) STEMdiff Neural Induction Medium+SMADi until the culture was terminated. Cells were passaged every 7days, and RNA was extracted from cells harvested at passages (days 7, 14, and 21).

Total RNA was isolated from hiPSCs or differentiated cells using the RNeasy Mini Kit (Qiagen) and treated with DNase I according to the manufacturers instructions. qRT-PCR was performed using a QuantiTect Probe One-Step RT-PCR Kit (Qiagen) on a STEPONEPLUS Real-Time PCR System (Applied Biosystems). The expression levels of target genes were normalized to those of the GAPDH transcript or 18S rRNA, which were quantified using TaqMan human Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) control reagents (Applied Biosystems) or eukaryotic 18S rRNA endogenous controls (Applied Biosystems), respectively. The probes and primers were obtained from Sigma-Aldrich. The used primer and probe sequences are listed in Supplementary Table 2. PCA was performed using SYSTAT 13 software (Systat Software Inc.) after data standardization (z-scoring) for each NS/PC marker gene.

To identify microarray probe sets related to the differentiation of hiPSCs into NS/PC, correlations between the intensity value rank of the filtered probe sets and the PC1 rank in the 10 hiPSC lines were determined by calculating Spearmans rank correlation coefficients (rs), as described in a previous study26. Probe sets exhibiting statistically significant correlations (P<0.01) were selected. When n=10 data points, the observed value of rs should exceed 0.794 (positively correlated) or less than 0.794 (negatively correlated) to be considered statistically significant (P<0.01).

ROR2 KD cells were generated by infecting R-2A cells with MISSION Lentiviral Transduction Particle expressing ROR2-targeted shRNAs (#1: TRCN0000199888, #2: TRCN0000001492) or MISSIONpLKO.1-puro Control Non-Mammalian shRNA Control Transduction Articles (Sigma, SHC002V), according to the manufacturers instructions. Media containing viruses were collected 48h after transfection, and the cells were transduced with the viruses using 8g/mL polybrene (Sigma-Aldrich) for 24h. The cells were selected using 2g/mL puromycin (Gibco) for 48h.

The cell lysates were used for western blotting analysis. Proteins were separated using sodium dodecyl sulfatepolyacrylamide gel electrophoresis, transferred to PVDF membranes (Bio-Rad), and blocked for 60min in Blocking One (Nacalai tesque). Primary antibody dilutions were prepared in Can Get Signal immunoreaction enhancer solution (TOYOBO) as follows: anti-ROR2 antibody (AF2064; R&D Systems) 1:1000, anti--actin antibody (A5441; Sigma-Aldrich) 1:2000. Membranes were incubated with HRP-conjugated anti-mouse IgG (Invitrogen) or anti-goat IgG (Invitrogen). Proteins were visualized using ECL Prime Western Blotting Detection Reagent (GE Healthcare) and the ChemiDoc Touch Imaging System (Bio-Rad).

HiPSC-derived NS/PC or forebrain neuron was fixed in 4% paraformaldehyde in PBS (Nacalai) for 20min at 25C. After washing with PBS, the cells were permeabilized with 0.2% Triton-X100 (Merk) in PBS for 15min and blocked with Blocking One (Nacalai) for 30min. The samples were incubated for 1h with primary antibodies (anti-PAX6 antibody [PRB-278P-100, BioLegend], anti-MAP2 antibody [MAB8304, R&D systems], and anti-GAD1 antibody [AF2086, BioLegend]). Indirect immunostaining was performed with the secondary antibody (anti-rabbit IgG/Alexa Fluor 555 [A27039, Thermo Fisher Scientific], anti-goat IgG/Alexa Fluor 488 [A32814, Thermo Fisher Scientific], and anti-mouse IgG/Alexa Fluor 488 [A28175, Thermo Fisher Scientific]) for 1h and examined under a BZ-X810 fluorescence microscope (Keyence).

ROR2 overexpression cells were generated by infecting 253G1 cells with lentiviral particles expressing ROR2. Briefly, the nucleotide sequence of the human ROR2 open reading frame (NM_004560) was de novo synthesized (Eurofins Genomics) and cloned into the pLVSIN-EF1 puromycin vector (Takara Clontech). Lentivirus packaging and virus infection were performed as described above.

Total RNA was extracted from hiPSC-derived NS/PC cells using an RNeasy Mini Kit (QIAGEN) according to the manufacturers instructions. Total RNA (100ng per sample) was used as the input for the Clariom D Assay (Thermo Fisher Scientific). Target preparation was performed using a Gene Chip WT PLUS Reagent Kit (Thermo Fisher Scientific) according to the manufacturers instructions. Hybridization was performed in a Gene Chip Hybridization Oven 645 for 16h at 45C. Gene chips were scanned using a GeneChip Scanner 3000. Array quality control was performed using Transcriptome Analysis Console software (version 4.0.2.15). The National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) accession number for the microarray data is GSE233228.

Differentiation of hiPSCs into mature nerves was performed according to the manufacturers instructions using the STEMdiff Forebrain Neuron Differentiation Kit (#08600, STEMCELL Technologies) for forebrain-type nerves and the STEMdiff Midbrain Neuron Differentiation Kit (#100-0038, STEMCELL Technologies) for midbrain nerves. Using the STEMdiff SMADi Neural Induction Kit (Stem Cell Technologies) monolayer culture protocol described above, hiPSCs were differentiated into NS/PC, and mature neural differentiation was induced.

For midbrain neuron differentiation, hiPSC-derived NS/PCs (day21, passage 3) were detached using Accutase and seeded into PLO (Sigma)-and laminin (Sigma)-coated 12-well plate at a density of 1.25105 cells/cm2 culture in STEMdiff Neural Induction Medium+SMADi medium for 24h. The complete medium was replaced daily for 6days with STEMdiff Midbrain Neuron Differentiation Medium. The midbrain neural precursors (day 7) were detached using ACCUTASE and seeded into PLO-and Laminin-coated 12-well plate at a density of 5104 cells/cm2 in STEMdiff Midbrain Neuron Maturation medium with a half-medium change every 23days for 14days.

For forebrain-type neuron differentiation, hiPSC-derived NS/PCs (day21, passage 3) were detached using Accutase and then seeded into PLO-and Laminin-coated 12-well plate at a density of 1.25105 cells/cm2 culture in STEMdiff Neural Induction Medium+SMADi medium for 24h. The full medium was replaced daily for 6days with STEMdiff Forebrain Neuron Differentiation medium. The forebrain neural precursors (day7) were detached using Accutase and seeded into PLO- and Laminin-coated 12-well plate at a density of 5104 cells/cm2 in STEMdiff Forebrain Neuron Maturation media with a half-medium change every 23days for 14days.

Statistical analyses were performed using Prism 9 software (version 9.5.1; GraphPad Software Inc.). Data are presented as meanstandard deviation (SD). For comparison between two groups the t-test was applied; in cases where another statistic test was applied, it is mentioned accordingly. Statistical significance was set at P<0.05.

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ROR2 expression predicts human induced pluripotent stem cell differentiation into neural stem/progenitor cells and ... - Nature.com

Consumers should beware of stem cell treatments for Covid-19 – BioEdge

By adminJanuary 8, 2024Stem Cell Clinics

A recent analysis has identified 38 companies offering so-called stem cell treatments and exosome treatments for preventing as well as treating COVID. These interventions are not supported by convincing safety and efficacy data; they have not been authorised by regulatory bodies such as the Food and Drug Administration (FDA).

The study, led by Professor Leigh Turner, from University of California, Irvine, also found that some of these dubious businesses are claiming to treat long Covid. This is often a debilitating condition that has no proven treatments at present. Some patients with long Covid may have physical symptoms including brain fog, fatigue and headaches that persist for months or possibly years. Desperate patients are extremely vulnerable to misleading claims made by such unscrupulous businesses due to the seriousness of the symptoms they are suffering.

As the human bodys master cells, stem cells have tremendous potential to repair and regenerate cells. However, these therapies have not been approved by regulatory groups. The FDA approved stem cell treatments for only some blood disorders but not for any other medical condition.

In 2021, the early days of the pandemic, Turner published a study regarding 1,480 American businesses promoting unlicensed stem cell-based interventions, some of which even claimed to prevent and treat Covid-19. In the present study, the companies continue to make those same claims while adding claims about long Covid; 36 of the 38 businesses in this analysis stated they had treatments for it. Six companies promoted them as immune boosters, five claimed to treat patients in the acute stage and two businesses stated their products were preventive. As means of advertising their products, some businesses resorted to social media like Facebook, Instagram, Twitter and TikTok. There were also promotional videos on YouTube.

The 38 companies are either operating or facilitating access to 60 clinics. Of the 60 clinics, 24 operate in the US and 22 in Mexico. Other clinics are in Ukraine, Guatemala, Malaysia, Panama, the Philippines, Poland, Spain, Thailand and the United Arab Emirates (UAE). Many of these treatments are costly between US$2,950 and $25,000. Some prices were stated as minimum costs, which suggests that the real expenses might be much more. Health insurance coverage generally does not cover stem cell interventions.

It is critical to have strict oversight as well as enforcement of the existing law. Regulatory bodies, such as the FDA and FTC (Federal Trade Commission) need to play their part enforcing the regulation. The FDAs Center for Biologics Evaluation and Research (CBER) is tasked with regulating cells, tissues and cellular and tissue-based products (HCT/P) which are intended for implantation, transplantation, infusion or transfer into a recipient. The agency has published detailed documents (good tissue practice, donor screening and donor testing requirements), to prevent the introduction, transmission and spread of communicable disease.

The FTC should pursue enforcement action against the clinics based on its jurisdiction over consumer protection issues such misleading and deceptive advertising. This agencys aims include the promotion of competition as well asprotecting and educating consumers. The commission should pursue a legal action when it has reason to believe that the violators are breaking or are about to break the law and it appears that bringing a lawsuit is needed as it is in the public interest. These federal bodies must implement various enforcement steps against these unscrupulous stem cell clinics. The measures should include warning letters and untitled letters and even suing these businesses.

There is at least one case that involves a lawsuit brought against a clinic that promoted stem cell products are treatments for Covid. In State of Washington v. US Stemology LLC and Tami Meraglia, it was alleged that US Stemology violated the states consumer protection legislation by deceptively promoting stem cell treatments of severe conditions, including Covid-19, without scientific basis. These claims were made at the start of the pandemic. A promotion from the company mentioned that a critically ill Covid patient recovered from the treatments. It also claimed a Free Coronavirus Thriving Guide that called stem cell treatment your personalised vaccine against getting sick with Covid-19.It stated, The reason for this is because stem cell therapy treats the lungs first and has long-term anti-inflammatory and immune modulating properties. Ultimately, the parties reached a settlement the company would pay $500,000 to the Attorney Generals Office, whichwill be distributed to the patients.

On a positive note, the National Institutes of Health (NIH) has begun several clinical trials on treating long Covid. Also the FDA has authorised stem cell clinical trials for long Covid. There has been a worrying surge of cases during this holiday period. Thus, patients with Covid, especially those with long Covid, need to shun these unscrupulous clinics peddling dubious treatments. Equally important, the various enforcement agencies need to do their part.

*******

Dr Patrick Foong is a senior law lecturer at Western Sydney University. His research interest lies in bioethics and health law.

Dr Alan W. Leung was a junior faculty at Yale University and Nationwide Childrens Hospital, and led iPSC product development at CRISPR therapeutics and Elevatebio. He is currently a freelance life science consultant and writer. His research interest lies in human embryonic stem cell therapy and preclinical applications.

Dr Patrick Foong is a senior law lecturer at Western Sydney University. His research interest lies in bioethics and health law.

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Consumers should beware of stem cell treatments for Covid-19 - BioEdge

Majority Leader Scalise to miss all of January as he undergoes stem cell treatment – Washington Examiner

By adminJanuary 8, 2024Stem Cell Treatment

House Majority Leader Steve Scalise (R-LA) will not return to Washington, D.C., until February as he undergoes a stem cell transplant as part of his cancer treatment, his office announced on Friday.

Last year, Scalise was diagnosed with multiple myeloma and underwent chemotherapy, which he completed in December. According to his office, Scalise had a positive response to the treatment and became eligible for an autologous stem cell transplant.

GOP TO PRESS FAUCI ON HANDLING OF SCIENTIFIC DEBATE IN FIRST POST-RETIREMENT TESTIMONY

He is currently undergoing the transplant process, marking a significant milestone in his battle against cancer. Once the procedure is completed, he will be recovering under the supervision of his medical team and will work remotely until returning to Washington next month. He is incredibly grateful to have progressed so well, and is thankful to his entire medical team, family, friends, and colleagues for their prayers and support, his office said in a statement.

With Scalise being gone for the month of January, it further dwindles House Republicans already slim majority during a month in which they are faced with a battle over must-pass legislation.

CLICK HERE TO READ MORE FROM THE WASHINGTON EXAMINER

When the House returns on Jan. 9, lawmakers will immediately be tasked with passing government funding, some of which will expire on Jan. 19.

Currently, House Republicans have a 220-seat majority. That will drop to 219 with Scalise gone and 218 when Rep. Bill Johnson (R-OH) leaves on Jan. 21. This will make it that much harder for leadership to pass legislation, which it was already struggling to get through the lower chamber.

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Majority Leader Scalise to miss all of January as he undergoes stem cell treatment - Washington Examiner

Global Stem Cell Therapy Market to Reach Value of USD 26.15 Billion by 2030 | Skyquest Technology – GlobeNewswire

By adminJanuary 8, 2024Stem Cell Treatment

Westford,USA, Jan. 02, 2024 (GLOBE NEWSWIRE) -- According to SkyQuest report, the global stem cell therapy market is experiencing substantial growth, primarily propelled by the increasing burden of chronic diseases such as cardiovascular disorders, neurodegenerative conditions, and orthopedic injuries. These debilitating ailments have placed a significant strain on healthcare systems worldwide.

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Browse in-depth TOC on the "Stem Cell Therapy Market"

The field of stem cell research has undergone a remarkable transformation driven by significant advances in technology and scientific understanding. These breakthroughs have broadened our knowledge of stem cells and expanded their potential applications in the global stem cell therapy market. Innovative methods for isolating, growing, and differentiating stem cells have been developed, facilitating their use in various therapeutic environments.

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Prominent Players in Global Stem Cell Therapy Market

Allogeneic Therapy Segment is Expected to Rise Significantly due to Increasing Popularity of Stem Cell Banking

Allogeneic therapy segment has emerged as the dominant force in the stem cell therapy market, commanding a substantial market share of 59.14% in 2022. This remarkable growth can be attributed to several key factors. Firstly, allogeneic therapies often come with higher pricing, contributing significantly to revenue generation. Moreover, the increasing popularity of stem cell banking, which involves collecting and storing allogeneic stem cells for potential future use, has driven demand for these therapies.

The market in North America has firmly established its dominance in the stem cell therapy market, commanding the largest revenue share at 44.56% in 2022. One key driver is the presence of innovative companies and major regional market players. North America is home to a robust and dynamic biotechnology and pharmaceutical industry, fostering stem cell therapy product development, production, and commercialization.

Autologous Therapy Segment is Expected to Dominate Market Due to Lower Risk of Complications

Autologous therapy segment is poised to experience significant growth over the forecast period, and several key factors contribute to this trajectory in the stem cell therapy market. One primary driver is the lower risk of complications associated with autologous treatments, as these therapies utilize a patient's stem cells, minimizing the chances of immune rejection or adverse reactions. Additionally, autologous therapies are often more affordable and accessible for patients, making them attractive.

Regional market in the Asia Pacific region is poised to become a significant growth driver in the stem cell therapy market, with a projected CAGR of 16.09% expected from 2023 to 2030. The region boasts a robust product pipeline of stem cell-based therapies, with ongoing research and development initiatives driving innovation.

A comprehensive analysis of the major players in the stem cell therapy market has been recently conducted. The report encompasses various aspects of the market, including collaborations, mergers, innovative business policies, and strategies, providing valuable insights into key trends and breakthroughs in the market. Furthermore, the report scrutinizes the market share of the top segments and presents a detailed geographic analysis. Lastly, the report highlights the major players in the industry and their endeavors to develop innovative solutions to cater to the growing demand.

Key Developments in Stem Cell Therapy Market

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Global Stem Cell Therapy Market to Reach Value of USD 26.15 Billion by 2030 | Skyquest Technology - GlobeNewswire

Choosing the Right Excipients for MSC and iPSC Therapies – Pharmaceutical Technology Magazine

By adminJanuary 8, 2024Stem Cell Treatment

Buffers, stabilizers, and cryoprotectants play major roles in cell therapy formulations.

While many stem-cell therapies remain at the preclinical stage, several are progressing through the clinic toward late-stage trials. Developing successful treatments based on induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) in part depends on creating effective formulations in which cell viability is maintained during cryopreservation, storage and handling, shipment, and reconstitution prior to delivery to the patient. Excipients, therefore, play an important role in bringing novel cell therapies to the market.

As with most biologic drug products, the predominant excipient in cell therapy formulations is the buffered saline solution. In this case, the saline solution is an osmotically balanced water solution designed to keep the cells from drying out and dying, according to Ryan Guest, senior CMC translation consultant for eXmoor pharma.

In addition to physiological saline, Carole Nicco, CSO at BioSenic notes that other isotonic solutions containing chemical substances present in blood, such as Ringers lactate, are also used to help maintain the electrolyte balance and keep the cells stable, sterile, and viable with proliferative capacity until their application. Furthermore, these isotonic solutions offer chemical easy systemic and local application, according to Nicco.

Classically, most formulations will also have protein to balance the solution as a buffer or reservoir for smaller molecules and enable transport via active protein transporters on cell membranes, Guest notes. The standard is an albumin (0.52.5%), such as human serum albumin. Albumin constitutes 5075% of the colloidal osmotic pressure of blood (13) and performs a very similar role in MSC and iPSC formulations, Guest says. More specifically, albumin is a useful component in cell therapy formulations for balancing water availability during product hold times, cryopreservation, and thawing prior to product administration.

In fact, Guest observes that the presence of an equivalent protein in cell therapy formulations is predicted to have a significant impact on cell survival. In MSCs, for instance, the absence of an appropriate protein can reduce viable recovery by 2040%, he comments.

The other important excipients for cell therapy products are cryoprotectants, given that the majority of these treatments are cropreserved. The cryopreservation of MSC- and iPSC-based therapies using 210% dimethyl sulfoxide (DMSO) in solutions containing ahigh content ofserum is a common procedure, Nicco observes. She adds that while DMSO has been used to reduce the formation of ice in cells stored in liquid nitrogen since 1959, it is toxic, resulting in undesired clinical and biological side effects. Serum also introduces variation and safety risks.

There is, consequently, Nicco says, a move toward solutions containing bio-preservation media free of DMSO, serum, and other proteins, optimized for the preservation and distribution of these products at low temperatures, either in cold (28 C) or cryopreserved conditions (-70 C to -196 C). The new excipients, she explains, eliminate toxicity issues as well as the need for human product excipients (serums, proteins) that can induce a risk of contamination to the drug product. Complex formulations involving dextran-40, lactobionate, sucrose, mannitol, glucose, adenosine, and/or glutathione are examples, according to Guest.

The type of stem cell therapy generally does not impact the choice of excipients, although Guest does note that some iPSCs can be more acutely sensitive to the final formulation, hold times, and routes of administration. For example, anucleated products, specifically designed to deliver payloads, have a reduced capability to produce proteins or perform cellular repair. Nicco adds that iPSCs and cells differentiated from them are commonly multicellular systems, which she says also makes them more sensitive to the stresses of freezing and thawing than single cells.

Overall, however, similar types of excipients are used for the preservation of cell-based therapies, regardless of the cell type or method of manipulation, according to Nicco. It is the route of administration, the need for transport, and the storage temperature that influence the choice of excipients, she states.

Special applications, for instance, such as therapies for artificial skins and wound healing may have specific properties or additional ingredients for sealing the wounds, Guest notes. Hence, the excipients or scaffolds are part of these therapies. Dosage size is another important factor, he adds. Larger doses need to take into account any toxic side effects of the excipients, such as DMSO, and may place maximal limits upon the total volume of excipients to be administered, he observes.

One of the most critical issues for cell therapy manufacturers is the maintenance of the cells in an appropriate medium/excipient from the end of the culture until the time of administration to the patient. Not only should the medium keep the cells viable with their properties intact, but the route of administration must also be taken into account, Nicco states. She adds that a good excipient is solvent-free and suitable for fresh or frozen suspensions of living cells formulated in a proprietary formulation adapted to the route of administration, such as intravenous, intra-articular, or intracranial.

In addition to understanding the delivery mechanism, Guest stresses the importance of considering the container and dose when choosing excipients. The next important factor, he says, is whether the cell therapy product will be supplied frozen, as that will require selection of a cryoprotectant. Formulation development experiments should then be designed carefully to optimize potency while taking into consideration hold periods and freeze/thaw steps and eliminating or otherwise minimizing the use of diluents and wash steps. In addition, Guest recommends evaluating existing administration formulations, containers, equipment, and protocols to minimize the need for new or changes to clinical practices.

An important component of any formulation strategy is consideration of the raw materials.For excipients intended for use in cell therapy products, Guest emphasizes the need to identify available good manufacturing practice (GMP)-suitable sources with acceptable lot-to-lot controls that will enable a reproducible product formulation. It is also critical, he says, to confirm the material is suitable for the manufacturing process and will be available to meet manufacturing demand for the cell therapy throughout its product life cycle.

Equally important, Guest observes, is to ensure the availability of suitable cellular material and drug product for designing formulation experiments. Understanding the patient group and the intended administration route are essential, meanwhile, for identifying potential side effects of any excipients.

Compendial excipients are generally preferred, Guest continues, due to the risk that novel or untested solutions will require significant development to ensure the material does not impact upon the therapeutic benefit of the cellular material. In addition, all materials including excipients must be suitable for the intended route of administration and present minimal risk of inducing toxicity, immune reactions, or the transfer of adventitious agents.

Controlling cellular material from the point of optimal donor selection to manufacturing under GMP conditions, commercialization, and application is critical for ensuring the quality, safety, and efficacy of the final drug product. While MSCs used as starting materials for production of advanced therapy medicinal products can only be isolated in authorized centers using globally standardized processes, the optimal conditions for culturing isolated MSCs are not standardized. That poses a major challenge in controlling their quality and therapeutic properties, Nicco contends.

It is, therefore, essential to control the cell sources (e.g., bone marrow, umbilical cord, and adipose tissue), cell density in culture, duration of culture, and cell engineering and composition of culture media and implement in-process quality controls that ensure cell efficacy and safety at all stages of manual and automated manufacturing processes, including cryopreservation, use of cell banks, and transport systems. Ultimately, the stability and quality of the cell therapy product and the excipients it contains must always be evaluated against reference samples submitted to the same storage facility, emphasizes Nicco.

Complicating this situation is the fact that it can be difficult to find reliable mode-of-action potency methods for cell-based therapies, according to Guest. Often both in vitro cell culture and in vivo models are required to confirm the suitability of the formulation, he says.

In addition, formulation strategy, hold times, cryopreservation, and thawing are intrinsically linked, and it can be difficult to determine the impact of each component of the formulation, Guest observes. Doing so requires carefully designed experiments and suitable analytical methods that assess not only the impact of formulation changes and freezing and thawing processes, but downstream biological mechanisms such as apoptosis and necrosis, which require time in a suitable cell-culture facility or in vivo models to optimize formulations, he explains.

A further difficulty rests with the fact that viability determinations are often tied to the analytical methods, the technicians performing them, and whether biological mechanisms of apoptosis and true cell recoveries are accounted for in the testing strategy, Guest comments. Therefore, it is important for cell therapy developers relying on external testing laboratories to ensure those outsourcing partners have the proper understanding, expertise, and capabilities needed for appropriate and comprehensive testing.

The cell therapy field is expanding at a rapid rate, and technology is advancing to support the increasing breadth of treatments under development. That includes formulation science and the development of enhanced excipient solutions. Cryoprotectants developed through biomimicry of natural antifreeze proteins to replace DMSO and serum protein-based media are one example highlighted by Nicco.

More work is to be done in this area, however. There is a clear unmet need for the discovery and development of novel cryoprotectants that can either replace or reduce the required amounts of current gold standards formulated to protect and treat challenging sample types such as MSCs and, even more, iPSC multicellular systems. This multivariate problem is complex, with multiple mechanisms of damage to be addressed and subtle differences between cell types and freezing methods. Combining high-throughput testing with iterative computational algorithms is key to optimizing protocols and excipient formulations to preserve emerging cell-based therapies, Nicco comments.

Guest, meanwhile, predicts that as the cell therapy field advances, clinical practice will naturally standardize formulation, delivery, and routes of administration through product safety and efficacy data. That will include the use of animal-free or recombinant excipients and other fit-for-purpose additives developed through the use of artificial intelligence to minimize cytotoxicity while improving stability and hold times, he states.

Nicco is also confident that the combination of new technologies such as intelligent library design, computational modeling, rapid screening assays, and advances in genomics will lead to a better understanding of the structure-function relationships between drug and excipient. That greater understanding will lead to more effective and efficient excipients that afford higher-performing cell therapies and ultimately benefit both cell therapy developers and patients, she concludes.

Cynthia A. Challener, PhD, is a contributing editor to Pharmaceutical Technology.

Pharmaceutical Technology Vol. 48, No. 1 January 2024 Pages: 2021, 25

When referring to this article, please cite it as Challener, C.A. Choosing the Right Excipients for MSC and iPSC Therapies. Pharmaceutical Technology 2024 48 (1).