Stem cell transplants found to extend survival by 4 years in ALS |… – ALS News Today

Transplants using mesenchymal stromal cells or MSCs a type of stem cell found in bone marrow delivered into the spinal canal can significantly extend survival in people with amyotrophic lateral sclerosis (ALS) compared with what would be expected based on their clinical characteristics, a new analysis of trials from the early 2000s found.

In two Phase 1 clinical trials that tested such stem cell transplants, the median time patients lived without requiring permanent ventilatory support was about 118 months, or nearly 10 years about four years longer than the roughly 70 months of predicted survival time pooled study data show.

At the time of the analysis, four patients (about 20% of participants) were alive, including one with a predicted survival of 91 months (about 7.5 years) who was alive at 303 months without needing a breathing or feeding tube. In other words, the patient was alive more than 20 years later.

The current study represents the first very long-term analysis of survival as an effect of MSC focal transplantation in the central nervous system [brain and spinal cord] of ALS patients, demonstrating that MSC transplantation could potentially slow down ALS progression and improve survival, the researchers wrote.

The study, Effect of mesenchymal stromal cell transplantation on long-term survival in amyotrophic lateral sclerosis, was published inCytotherapy.

ALS is a rare neurodegenerative disease marked by the progressive loss of motor neurons, the nerve cells that control voluntary movements. There is no cure to date, and few effective treatments are available to slow disease progression.

MSCs, also called mesenchymal stem cells, are a form of stem cells that can give rise to several connective tissue cells, such as fat cells and blood vessel cells.

These cells also can produce a range of signaling molecules that modulate immune responses and have tissue-protective and regenerative properties. As such, their use is considered a potentially promising approach for treating ALS.

The safety and feasibility of transplanting MSCs into the spinal canal has been established in ALS clinical trials. But few studies have reported the long-term effects of these cells in patients.

To address that, and eventually support a Phase 2/3 trial, researchers in Italy examined the long-term outcomes of ALS patients treated with MSCs in clinical trials conducted in the early 2000s. Specifically, the two Phase 1 clinical trials reviewed here were conducted by the team in 2002 and 2006.

Nineteen patients were treated in these studies, with nine involved in the first trial and 10 in the second.

For each patient, the team calculated survival defined as time to permanent non-invasive ventilation, breathing tube, or death using the European Network to Cure ALS (ENCALS) model. This tool predicts survival based on certain clinical characteristics, including age at disease onset, lung function, any delay in diagnosis, the rate of disease progression, and the presence of certain ALS-related mutations.

The expected survival for each patient based on this model was then compared with the individuals actual survival time.

The results showed MSC treatment significantly extended the patients lives compared with what would be expected based on their clinical characteristics. While the ENCALS model estimated a median survival of 70.8 months, patients actually lived for 118.8 months on average four more years than estimated.

The current study represents the first very long-term analysis of survival as an effect of MSC focal transplantation in the central nervous system [brain and spinal cord] of ALS patients, demonstrating that MSC transplantation could potentially slow down ALS progression and improve survival.

Of the total 19 patients, 13 (68%) had a longer survival time than expected. One patient had been classified as having a short survival and transitioned to intermediate, and three were intermediate and ended up having a long-to-very-long survival. The other nine were classified as very long survival, but still ended up living for more months than expected.

The survival extension was particularly evident in a group of patients with slow disease progression, 80% of whom lived longer than expected. Among those with fast progression, only 55% had longer survival than estimated; the other 45% lived less time than expected.

At the time of the analysis, four patients were still alive, including one who started noninvasive ventilation 35 months (nearly three years) after treatment and one who is still living without the need for ventilatory support. The other two patients have required a tracheostomy a procedure in which a tube is fitted through a hole in the neck to help with breathing.

Together, these results show a potential for stem cell transplants with MSCs to slow disease progression and improve survival in ALS patients, providing new insights for planning the next generation of efficacy MSCs clinical trials in ALS, the researchers wrote.

The team noted that stem cell transplantations role in ALS still needs further understanding. But the researchers hypothesized that the observed clinical effects could be primarily based on modifying the extra-motor neuron environment, such as through the release of trophic factor and the modulation of neuroinflammation.

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Professor Neil Hanley to become new Head of the College of … – University of Birmingham

The University of Birmingham has appointed Professor Neil Hanley as Pro-Vice-Chancellor and Head of the College of Medical and Dental Sciences

The University of Birmingham has appointed Professor Neil Hanley as Pro-Vice-Chancellor and Head of the College of Medical and Dental Sciences.

Professor Hanley, who is currently Vice-Dean (Research and Innovation) in the Faculty of Biology, Medicine and Health at the University of Manchester and an Honorary Consultant Endocrinologist at Manchester Royal Infirmary, will take up his new role from 1 September 2023.

Professor Adam Tickell, Vice-Chancellor of the University of Birmingham, said:

I am delighted to announce that we have found the next leader of our College of Medical and Dental Sciences. In Neil, we have an excellent clinician, educator, and researcher with an enviable CV, who will bring energy and experience to this important role.

Professor Hanley holds a BSc in Pharmacology, an MBChB from the University of Edinburgh, and a PhD in Molecular Genetics from Newcastle University. He was first made full professor in 2006 and is a past president of the Association of Physicians of Great Britain and Ireland. He has been at The University of Manchester since 2008, becoming Director of Research and Innovation at Manchester University NHS Foundation Trust in 2016, and Vice-Dean (Research and Innovation) in 2020.

There is a real sense of ambition at the University, making it an honour and a very exciting time to be joining the mission to change lives for the better through education and research.

Professor Hanley said:

The University of Birmingham has a strong track record for improving the health of people locally and across the world through new discoveries, treatments, and training the next generation of healthcare practitioners. There is a real sense of ambition at the University, making it an honour and a very exciting time to be joining the mission to change lives for the better through education and research.

An expert in early human development and stem cell biology, Professor Hanley has held doctoral, intermediate, and senior clinical fellowships from NIHR or Wellcome, and additional funding as lead investigator from MRC, BBSRC and EPSRC, among others. Over the last decade, this has led to outputs in several Nature journals, eLife, and PNAS. His current partnership as chief investigator with Innovate UK and industry leaders has translated his collaborative discovery science into integrated novel diagnostics for the early detection of liver disease.

Professor Hanley has a passion for education and training, having established an academy in Manchester for those embarking on their own research careers. He also directs the Wellcome-funded PhD programme for healthcare professionals across the universities of Leeds, Manchester, Newcastle and Sheffield, and led the future vision of NIHRs 2016 national review of training.

The University of Birminghams College of Medical and Dental Sciences is shaping the future of health and medicine through the provision of innovative education and exceptional research, both delivered by world-leading academics. Earlier this year, the University of Birmingham rose 30 places in the QS World Subject Rankings for Life Sciences and Medicine and is now ranked at number 62.

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Identification of tunnels connecting neurons in the developing brain – Science Daily

Over a hundred years after the discovery of the neuron by neuroanatomist Santiago Ramn y Cajal, scientists continue to deepen their knowledge of the brain and its development. In a publication in Science Advances on April 5, a team from the Institut Pasteur and the CNRS, in collaboration with Harvard University, revealed novel insights into how cells in the outer layers of the brain interact immediately after birth during formation of the cerebellum, the brain region towards the back of the skull. The scientists demonstrated a novel type of connection between neural precursor cells via nanotubes, even before the formation of synapses, the conventional junctions between neurons.

In 2009, Chiara Zurzolo's team (Membrane Traffic and Pathogenesis Unit at the Institut Pasteur) identified a novel mechanism for direct communication between neuronal cells in culture via nanoscopic tunnels, known as tunneling nanotubes. These are involved in the spread of various toxic proteins that accumulate in the brain during neurodegenerative diseases. Nanotubes may therefore be a suitable target for the treatment of these diseases or cancers, where they are also present.

In this new study, the researchers discovered nanoscopic tunnels that connect precursor cells in the brain, more specifically the cerebellum -- an area that develops after birth and is important for making postural adjustments to maintain balance -- as they mature into neurons. These tunnels, although similar in size, vary in shape from one to another: some contain branches while others don't, some are enveloped by the cells they connect while others are exposed to their local environment. The authors believe these intercellular connections (ICs) may enable the exchange of molecules that help pre-neuronal cells physically migrate across various layers and reach their final destination as the brain develops.

Intriguingly, ICs share anatomical similarities with bridges formed when cells finish dividing. "ICs could derive from cellular division but persist during cell migration, so this study could shed light on the mechanisms allowing coordination between cell division and migration implicated in brain development. On the other hand, ICs established between cells post mitotically could allow direct exchange between cells beyond the usual synaptic connections, representing a revolution in our understanding of brain connectivity. We show that there are not only synapses allowing communication between cells in the brain, there are also nanotubes," says Dr. Zurzolo, senior author and head of the Membrane Traffic and Pathogenesis Unit (Institut Pasteur/CNRS).

To achieve these discoveries, the researchers used a three-dimensional (3D) electron microscopy method and brain cells from mouse models to study how the brain regions communicate between each other. Very high resolution neural network maps could thus be reconstructed. The 3D cerebellum volume produced and used for the study contains over 2,000 cells. "If you really want to understand how cells behave in a three-dimensional environment, and map the location and distribution of these tunnels, you have to reconstruct an entire ecosystem of the brain, which requires extraordinary effort with twenty or so people involved over 4 years," said the article's first author Diego Cordero.

To meet the challenges of working with the wide range of cell types the brain contains, the authors used an AI tool to automatically distinguish cortical layers. Furthermore, they developed an open-source program called CellWalker to characterize morphological features of 3D segments. The tissue block was reconstructed from brain section images. This program being made freely available will enable scientists to quickly and easily analyze the complex anatomical information embedded in these types of microscope images.

The next step will be to identify the biological function of these cellular tunnels to understand their role in the development of the central nervous system and in other brain regions, and their function in communication between brain cells in neurodegenerative diseases and cancers.The computational tools developed will be made available to other research teams around the globe.

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BetaLife and A*STAR Agree to Focus on Novel Cell-Based Therapy … – Genetic Engineering & Biotechnology News

BetaLife agreed to collaborate with the Agency for Science, Technology and Research (A*STAR), both organizations based in Singapore, to accelerate the development of next generation cell-based therapy for diabetes.

BetaLife, a stem cell therapy company focused on developing regenerative medicine for diabetes, has acquired the rights to human induced Pluripotent Stem Cell (iPSC) technology from A*STAR. The technology enables the generation of iPSCs to provide a renewable and sustainable human stem cell resource to generate any mature cell type of interest, according to a BetaLife spokesperson who adds that such iPSC-derived cells can potentially be used to regenerate or replace defective tissues in human patients.

According to the International Diabetes Federation, over 530 million people worldwide live with diabetes, and human iPSC-based technology could potentially provide a curative treatment for this chronic disease.

BetaLife and A*STAR plan on generating highly curated human iPSC banks that capture the genetic diversity of Asian ethnicities and on developing human iPSC-derived pancreatic islet cells. The collaboration combines A*STARs capabilities in stem cells and diabetes biology with BetaLifes infrastructure and proprietary platforms for the scaleup and therapeutic development of an off-the-shelf human iPSC-based therapy.

Pancreatic beta cells derived in the lab from human iPSCs not only provide a cell model for diabetes research but may even be developed into a regenerative medicine product to help patients regain control of their blood glucose levels, points out Adrian Teo, PhD, principal investigator at the A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB) and scientific co-founder of BetaLife.

Diabetes is prevalent among Singaporeans. It is heartening to witness how A*STARs R&D is able to empower local biotech companies to advance treatment for diabetes patients and contribute towards better health and societal outcomes, says Hong Wanjin, executive director at A*STAR IMCB.

For more on stem cells see GEN: Stem Cells May Move to the Front Line Against Multiple Sclerosis and 3D Bioprinting and Stem Cells Help Create Model of Eye Diseases.

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OMRF researcher named scientific director of OCASCR | Community … – Duncan Banner

OKLAHOMA CITY The Oklahoma Center for Adult Stem Cell Research (OCASCR) has named Oklahoma Medical Research Foundation scientist Lorin Olson, Ph.D., as its new scientific director.

OCASCR was founded in 2010 by the Oklahoma Tobacco Settlement Endowment Trust (TSET) to increase adult stem cell research in Oklahoma. Since then, OCASCR has funded research projects on diabetes, blindness, cancer and other illnesses at OMRF, Oklahoma State University, the University of Oklahoma and the OU Health Sciences Center.

Olson earned his undergraduate degree from Brigham Young University and his doctorate in biomedical science from the University of California, San Diego. Following postdoctoral training at the Fred Hutchinson Cancer Research Center in Seattle and the Mount Sinai School of Medicine in New York City, Olson launched his lab at OMRF in 2010. His work in the Cardiovascular Biology Research Program focuses on the intricate process of wound repair and the genes that control connective tissue development and disease.

Olson succeeds OMRFs recently appointed vice president of research, Courtney Griffin, Ph.D., as OCASCRs scientific director. In that role, he will oversee a semiannual review of grant applications from Oklahoma scientists to fund studies and equipment needed for specific research.

Olson plans to continue OCASCRs focus on adult stem cell research and regenerative medicine. Regenerative medicine is looking at how to use adult stem cells or their by-products to repair and restore diseased or damaged organs. Thats especially important in diseases related to smoking and obesity, both of which are focuses of TSET, he said.

TSET Executive Director Julie Bisbee said she is excited about the future of OCASCR and the role this research plays in TSETs overall goal.

TSET is proud to support OCASCR as their researchers develop new treatments for cancer and other tobacco-related diseases, said Bisbee. That work is key to TSETs mission and helps support scientific research and discoveries in Oklahoma. The work of this unique collaboration between academic and research institutions will be felt for generations to come.

Since OCASCRs founding, TSET has invested $31 million in Oklahoma scientists focused on adult stem cell research, with a return on that investment of more than $280 million in grants resulting from projects launched through the initiative.

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Blindness from Retinitis Pigmentosa reversed with MD Stem Cells treatment- benefit may last years – EIN News

RP patient improves from legal blindness to 20/20 vision following MD Stem Cell Treatment- wants to repeat

Steven Levy MD

WHAT'S NEW: The stem cell approach pioneered by MD Stem Cells has shown positive results helping patients suffering from a number of eye and neurologic diseases. In one of their initial scientific papers, MD Stem Cells showed that patients with Retinitis Pigmentosa or RP could benefit from the treatment provided in the Stem Cell Ophthalmology Treatment Study. That paper is titled Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of Retinitis Pigmentosa. We now see that these improvements can achieve normal acuity that results can last many years.

ACTUAL RESULTS: Results reported were all statistically significant- the gold standard in medicine for confirming results. 64.7% of patients showed improved binocular vision averaging 10.23 lines of Snellen acuity per eye over pre-treatment acuity; 35.3% of patients remaining stable over the follow up period. Improvements ranged from 1 to 27 lines of vision. Using the Logmar Scale visual acuity improvement ranged from 23% to 90% with an average of 40.9% visual acuity improvement over baseline vision. MD Stem Cells unique approach is the first and only treatment to actually improve and maintain vision in patients with RP.

WHAT IS THE TREATMENT: The Stem Cell Ophthalmology Treatment Study II ( SCOTS2) uses the patient's own stem cells for treatment. The patient is provide a short period of anesthesia and there is no pain. They take a small amount of the patients own bone marrow, isolate the stem cells, and provide 2 ocular injections followed by intravenous. .

OTHER EYE DISEASES THIS CAN HELP: MD Stem Cells has treated a number of eye diseases with benefit to vision. Retinal conditions such as dry AMD (macular degeneration), Retinitis Pigmentosa, Usher, Stargardt, Cone-Rod, Rod-Cone, Cone dystrophies, Bests dystrophy, different retinal problems including retinopathy, injury, inflammation, POHS ,choroiditis, some diabetic retinopathies and certain post Retinal Detachment vision loss. A number of optic nerve conditions have also responded including Glaucoma, LHON, Dominant Optic Atrophy, Optic neuropathies and many other optic nerve problems.

KEY POINTS: Retinitis Pigmentosa can now be treated with the SCOTS2 procedure with a high, statistically significant chance of improvement. Contact MD Stem Cells directly for a case review. MD Stem Cells has vast experience with eye disease and has published multiple medical and scientific papers. This is reassuring to patients and health care providers seeking treatment options. MD Stem Cells has the knowledge to carefully treat your retinal or optic nerve condition, if appropriate, leading to optimal results.

I WANT MORE INFORMATION: Receive information about participating in SCOTS2 by emailing Dr. Levy at stevenlevy@mdstemcells.com with your name, cell phone, email address and brief history of their disease. You may also use the contact us page on http://www.mdstemcells.com or call directly 203-423-9494. MD Stem Cells has no grant support and is not a pharmaceutical company; this is a patient sponsored studies and the patients pay for both treatment and travel.

Steven Levy MDMD Stem Cells+1 203-423-9494stevenlevy@mdstemcells.com

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Researchers develop method to identify, sort and observe function in neural stem cells – Medical Xpress

This article has been reviewed according to ScienceX's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

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by Justin Jackson , Medical Xpress

Graphical abstract. Credit: Cell (2023). DOI: 10.1016/j.cell.2023.02.017

Researchers at Stanford University in California have devised a fluorescence-activated cell-sorting method for isolating distinct neural stem and progenitor cell types from human brain tissue. The markers used in the study are conserved across diverse brain regions. The technique should aid future research on neurodevelopment and accelerate the development of neuronal cell-transplantation-based therapeutic regimens to treat a host of neurological disorders.

In the research article, "Purification and characterization of human neural stem and progenitor cells," published in the journal Cell, the Stanford team describes the combination of cutting-edge methods they used to develop a reliable isolation and identification scheme to capture the stem cells of interest.

The human brain is home to about 171 billion individual cells, with just over half (~86 billion) being neuronal cells. Those 86 billion neuronal cells are a diverse group, with hundreds of dedicated types and functions, but all originate from three neuronal lineagesneurons, oligodendrocytes and astrocytes. The three lineages all start from a pool of neural stem and progenitor radial glia cells that undergo rapid development during the second trimester of prenatal gestation. Understanding these radial glia cells, how they differentiate into the three lineages and how the three lineages differentiate into the diverse range of neuronal cells would be of enormous benefit to medical research.

Fluorescence-activated cell sorting was used to separate brain tissue cell types by cell surface immunophenotype from a suspension of single cells. The cells were indexed (fluorescence recorded) and isolated from each other. The cells were then submitted to single-cell RNA sequencing to capture their individual transcriptomes. By combining the surface-marker profile with indexing and transcriptome, the researchers now had a profile of each cell type that could be used for later identification. Researchers also measured the expression of 352 additional surface markers not used in the initial separation scheme but which could be used to better differentiate cells in the future.

Index-sort data allowed for each sequenced cell to be mapped back to its original immunophenotype and the researchers discovered that RNA and cell-surface protein expression did not always correlate. Some similar looking cells might have different functions. The strategy resulted in functionally similar populations of sorted cells allowing for the isolation of specific neural stem and progenitor cell type functions to be analyzed.

Ten neural stem and progenitor cell types were identified, and the researchers looked to characterize the behavior of the cells by transplanting them directly into the brains of neonatal immunodeficient mice. After six months, the cells had migrated and engrafted extensively throughout the brain and differentiated to give rise to all three major neural lineages. By observing how and where individual cell types propagated, the researchers could make some initial inferences about site-appropriate activities. Though the experiment was meant simply as a method viability test, researchers did identify and functionally characterize a distinct bipotent glial progenitor cell that had not been previously described.

The Stanford team's successful proof of concept (with a discovery) that distinct cell types from the developing brain can be isolated based on surface markers could be readily adapted by other research scientists, as it operates on relatively standard research equipment. If the method used can be replicated for other stem cell types, there could be a surge in our understanding of specific functions, mechanisms and hierarchical roles that cells play in the brain or in other organs.

More information: Daniel Dan Liu et al, Purification and characterization of human neural stem and progenitor cells, Cell (2023). DOI: 10.1016/j.cell.2023.02.017

Journal information: Cell

2023 Science X Network

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Researchers develop method to identify, sort and observe function in neural stem cells - Medical Xpress

Using stem cells to prevent brain damage in very preterm babies – Monash University

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21 March 2023

Australian researchers have conducted the first attempts to collect umbilical cord blood cells from very preterm babies, with a view to using them to reduce their increased risk of brain injury and disability.

The trial was conducted at Monash Childrens Hospital Melbourne, Australia, led by Dr Lindsay Zhou, under the supervision of Professor Atul Malhotra, Co-Director of the Newborn Cell Therapies Group from the Department of Paediatrics at Monash University and published recently in the journal Cytotherapy.

Cord blood is the blood left in the umbilical cord and placenta of newborn babies after birth. It is rich in stem cells which can be used to help protect, repair and grow cells in the body, and according to Dr Zhou these cells have shown strong promise as a treatment for neonatal brain injury in pre-clinical models and early-phase clinical trials. While it has been tested in infants born at term, these life-giving cells have not been tested in preterm babies, who arguably have the greatest need for new treatments because their risk of brain injury and disability later in life is so much greater, he said.

The researchers, who are also from The Ritchie Centre at the Hudson Institute of Medical Research, took cord blood from 38 infants born before 28 weeks gestation. Babies born extremely preterm (<28 weeks) have a high chance of long-term developmental issues, including cerebral palsy, and learning and behavioural issues.

Of the babies included in the trial, 21 were male and 17 female. Twenty-four (63.1%) were delivered via caesarean section, and 11 (28.9%) were a multiple birth. The average age of the baby in this study was 26 weeks gestation, and the average birth weight was 761.5 grams.

The researchers were able to collect an average of 19 ml/kg of cord blood from these preterm babies, which is similar to term babies by body weight. The procedure was successful in 72% of cases. According to Professor Malhotra, these findings are important because we have shown we can collect these cells in extremely small babies, and can now use them in the CORD-SAFE study currently underway at the Monash Childrens Hospital.

The CORD SAFE study is investigating the feasibility and safety of administering autologous (their own) cord blood cells to these extreme premature infants. The study is nearing completion phase, with results likely by the end of the year.

Read the full paper in Cytotherapy journal titled: Feasibility of cord blood collection for autologous cell therapy applications in extremely preterm infants.

DOI: 10.1016/j.jcyt.2023.01.001

About Monash University

Monash University is Australias largest university with more than 80,000 students. In the 60 years since its foundation, it has developed a reputation for world-leading high-impact research, quality teaching, and inspiring innovation.

With four campuses in Australia and a presence in Malaysia, China, India, Indonesia and Italy, it is one of the most internationalised Australian universities.

As a leading international medical research university with the largest medical faculty in Australia and integration with leading Australian teaching hospitals, we consistently rank in the top 50 universities worldwide for clinical, pre-clinical and health sciences.

For more news, visitMedicine, Nursing and Health Sciences orMonash University.

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Cell Therapy Prevents Risk Of Heart Attack or Stroke: Study – Forbes

All organs in the body rely on the blood and oxygen circulated by the heart. If the muscles of the heart weaken or stiffen too much, the heartalthough still beatingcan no longer pump enough to sustain other organs. This progressive condition called heart failure presently affects more than 6 million adults in the United States. Current treatments can delay but not permanently alter the course of the disease, leaving many patients with poor prognoses. A recent study published in the Journal of the American College of Cardiology searches for a permanent solution to repair the heart via stem cell therapy.

What are Mesenchymal Stem Cells?

Mesenchymal precursor cells (MPCs) refer to a small population of adult stem cells found in the bone marrow and select tissues. While embryonic stem cells can develop into any cell type in the body, mesenchymal stem cells develop into a defined variety of specialized cells. As Figure 1 illustrates, differentiation of these cells can create connective tissue cells, cartilage cells, white fat cells, bone cells and muscle cells. The ability to regenerate muscle cells is of notable interest in discussions around healing damaged hearts.

Mesenchymal precursor cells demonstrate other unique abilities. Preclinical studies suggest that these precursor cells may reduce inflammation driven by macrophages, immune cells involved in the bodys healing processes, and chemicals called cytokines. These stem cells also release proteins which promote the growth of new blood vessels and reverse the narrowing of arteries. These two characteristics may address critical mechanisms which contribute to heart failure: acute and chronic inflammation alongside restricted blood flow to the hearts tissues.

Clinical Trial Design

For their study, Perin et al. assessed the efficacy of mesenchymal precursor cell therapy on over 500 patients with moderate to severe heart failure. To do this, they first crafted their stem cell product. The researchers derived the stem cells from the bone marrow of three healthy adult donors. They then isolated and proliferated the stem cells before preserving them in liquid nitrogen.

Of all the hearts chambers, the team focused on the left ventricle. Figure 2 highlights the structure. This section of the heart provides the most pumping power and often falters first for people with heart failure. Left ventricular performance is therefore an important marker of the hearts condition.

Half of the study population received at least one dose of the cell therapy injection (see Figure 3) into the left ventricle. In contrast, the other halfthe control groupunderwent a procedure to remove a catheter from the left ventricle. The researchers then conducted site follow-ups 10 days after and on months 1, 3, 6 and 12. After month 12, the patients returned to the site every six months. The team followed the patients for around 30 months on average.

Study Endpoints and Measurements

The study contained two main objectives to understand the potential benefits of the intervention. The primary endpoint measured whether the therapy prolonged the time to a patients next nonfatal hospitalization or urgent care visit; it was considered a terminal event if a patients left ventricle failed to provide the majority or any of the hearts output. The secondary measurement recorded both the primary endpoint and the time to death.

Guided by a previous study, the team monitored left ventricular function and markers of inflammation for additional analysis. Left ventricular performance plays a major role in determining heart failure, while high baseline levels of high-sensitivity C-reactive protein (hsCRP)a marker of inflammationin patient plasma is associated with adverse cardiac events.

Mixed Results

The clinical trial yielded mixed results. The team found no significant difference between the treatment groups for the studys primary and secondary endpoints, suggesting that the therapy did not succeed. However, the therapy produced major findings related to heart function which hold great promise for future research.

Inflammation, Heart Attack and Non Fatal Stroke

The team noticed that adverse heart events could be stratified by inflammation. A single stem cell injection resulted in a 67% reduction in heart attack and a 56% reduction in stroke compared to controls. Figure 4 illustrates the clear difference in risk. Interestingly, the supposed benefit increased if the patient displayed higher levels of inflammation (see Figure 5).

Additionally, the therapy led to a modest reduction38% specificallyin three point major adverse cardiovascular events. This is categorized by a cardiovascular death, nonfatal heart attack or nonfatal stroke. Patients with more detectable inflammation saw a larger effect here, as well.

Inflammation and the Left Ventricle

The team used echocardiographic imaging to glean information about the left ventricle. They recorded three measurements in particular: left ventricular ejection fraction (LVEF), or how much blood the left ventricle pumps out during each heartbeat; left ventricular end-systolic volume (LVESV), or how blood remains in the chamber after a heartbeat; and left ventricular end diastolic volume (LVEDV), how much blood is in the chamber before a heart beat.

The patients who received the cell therapy experienced a small but statistically significant improvement in their hearts ability to pump over the course of a year. This is mostly attributed to the effect experienced by patients with higher levels of inflammation. In comparison, the therapy did not influence the left ventricular diastolic volume when compared to controls.

Possible Mechanisms

The clinical hope for cell therapy is to harness the self-renewing and tissue regenerating capabilities of stem cells to heal and repair the body. The mesenchymal stem cells injection in this study did not meet this goal; the therapy failed to reduce time to nonfatal hospitalization and all cause death for patients with heart failure. However, an interesting discovery did emerge regarding inflammation.

The stem cell therapy created by Perin et al. yielded larger perceived benefits for patients with higher detectable levels of inflammation. Heart attack, stroke and left ventricular function appeared to improve for patients with evidence of systemic inflammation. How could this difference be explained?

Background research suggests that targeting inflammation could reduce negative heart events. Animal studies of heart failure demonstrated how mesenchymal precursor cells could rebuild and generate new blood vessels; they, too, could reverse the narrowing of arteries throughout the heart and body in the presence of systemic inflammation. The authors posit, then, that their cell therapy may alter inflammatory environments in the heart and promote blood flow through the formation of new blood vessels.

The cytokines found around the heart may activate the mesenchymal cells, causing the stem cells to subsequently release proteins which suppress inflammation and encourage blood vessel formation. The anti-inflammatory effects likely reduce nonfatal heart attack, stroke and death for patients with high inflammation. On the other hand, the new blood vessels likely improve the function of the left ventricle, as noted in the study.

As the stem cells appear to target local and systemic inflammatory changes seen in heart failure and atherosclerosis (plaque-filled arteries), Perin et al. turn to inflammation as a possible therapeutic target for heart failure. The therapy, when used in conjunction with existing heart failure treatments, may provide additional clinical benefit to patients with increased inflammation.

Future Implications

This clinical trial marks an important step in the journey to use cell therapy to reverse heart failure. Although the therapy did not prevent hospitalization as initially hoped, the researchers found that a single stem cell injection reduced the risk of heart attack or stroke by more than 50% for people with heart failure. Stem cell therapy may be a complementary addition to heart failure treatment regimes in the future, but further research is needed to ascertain its promise.

I am a scientist, businessman, author, and philanthropist. For nearly two decades, I was a professor at Harvard Medical School and Harvard School of Public Health where I founded two academic research departments, the Division of Biochemical Pharmacology and the Division of Human Retrovirology. I am perhaps most well known for my work on cancer, HIV/AIDS, genomics and, today, on COVID-19. My autobiography, My Lifelong Fight Against Disease, publishes this October. I am chair and president of ACCESS Health International, a nonprofit organization I founded that fosters innovative solutions to the greatest health challenges of our day. Each of my articles at Forbes.com will focus on a specific healthcare challenge and offer best practices and innovative solutions to overcome those challenges for the benefit of all.

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Cell Therapy Prevents Risk Of Heart Attack or Stroke: Study - Forbes

Rise in Prostate Cancer Cases Contributes to Challenges in Care – Targeted Oncology

Murugesan Manoharan, MD, FRACS

Troubling news about prostate cancer emerged from the American Cancer Society (ACS) in January. In its Cancer Statistics 2023 study1, published in the journal CA: A Cancer Journal for Clinicians, ACS scientists announced:

These findings are due in part to the US Preventive Services Task Forces 2012 recommendation to cease PSA screening in all men. Since then, early diagnosis and treatment of prostate cancer has dropped, while advanced prostate cancer cases have begun a steady rise.

I have observed several factors in play at Miami Cancer Institute as we respond to the challenge of prostate cancer.

Cost of PSA Screening

I concur with the ACS recommendation that men of all ages should have an opportunity to make an informed decision about whether prostate cancer screening is right for them. Balanced and unbiased counsel from the physician is vital. However, the cost of testing may be a barrier for some patients, as many insurance plans do not cover it. I have observed that wealthier patients in urban areas are more likely to have access to timely screening, while lower-income and minority individuals do not. The latter group includes many of my patients in the Haitian American community, who have a significant incidence of aggressive prostate cancer.

Plentiful Treatment Options

The array of prostate cancer treatments includes robotic surgery, external beam radiation including proton beam therapy, brachytherapy, cryotherapy, high-intensity focused ultrasound (HIFU), laser ablation, hormone and other drug therapy, chemotherapy, immunotherapy, and more. Direct-to-consumer marketing touting these various treatments can confuse and overwhelm patients. Again, careful consultation with an unbiased urologic oncologist is critical.

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FDA Reviews

While the US is quite advanced in prostate cancer treatment, The FDAs ultra-cautious approach to approvals results in a lag in new-technology adoption.

For example, prostate specific membrane antigen (PSMA PET Imaging, which can accurately detect the spread of prostate cancer spread using a radioactive tracer, has been in use internationally since around 2014, but the FDA delayed its broad national approval of this technology until 2021.

High Intensity Focused Ultrasound (HIFU) therapy was studied as early as the 1940s and researchers focused on HIFU for the prostate in the 1990s. The treatment was approved in more than 20 countries, including Canada and Australia, before finally receiving FDA approval in 2015.

Last, the NanoKnife system, which employs low-energy, direct-current electrical pulses to destroy cancerous cells,was first made commercially available in 2009 but the FDA approved a pilot study only in 2019.

These technologies were widely used in cancer centers around the US prior to full FDA approval but since they werent covered by insurance, they were out of reach for many patients who could have benefited.

Promoting Good Quality-of-Life

Death isnt the only outcome of a prostate cancer diagnosis. The statistics dont account for the pain, suffering, and inconvenience patients may endure while undergoing treatment. My team and I focus on helping patients maintain a good quality of life while we work towards a cure. Our patients express several priorities as they prepare for prostate cancer treatment:

A quick recovery: patients want to get back to work and everyday living. Technological advances such as minimally invasive surgery (sometimes with a single small incision) help make this possible. Many patients go home 24 hours after surgery. Once their pain can be managed without narcotics, they can usually resume driving and other daily tasks.

Reliable urinary function: patients frequently express concerns about incontinence. Twenty years ago, some 10 percent of patients were left incontinent by prostate surgery. Because we are now able to better protect the nerve bundles and urinary sphincter during surgery, 98 percent of patients do not need pads one year after surgery.

A healthy sex life: while measuring sexual potency is subjective, I advise patients that if they are potent before surgery, theres a 75 to 90 percent chance they will remain potent after nerve-sparing surgery.

Managing treatment: traditional radiation treatments can require up to 6 weeks of daily hospital visits, a burdensome task for patients who are trying to hold down a job. Hyperfractionated radiotherapy uses higher doses of radiation spread over fewer days, allowing patients to keep a regular work schedule. Ablation therapy requires even less of a time commitment.

Novel treatment strategies

Novel treatment like theranostics are on the rise. Theranostics combines therapeutic, radioactive pharmaceutical particles with diagnostic imaging to examine cancerous cells. In prostate cancer patients, a PSMA PET scan is done to evaluate for metastatic disease. PSMA, or prostate-specific membrane antigen, is expressed by virtually all prostate cancers and its presence locates the cancerous cells accurately. When these cells and receptors are located, a theranostic medicine such as Lutetium-177 in combination with PSMA is administered, which binds to and kills the cancerous cells. Its use is currently limited to prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer.

Training

As prostate cancer diagnoses continue to rise, todays physicians have a duty to prepare the next generation in the fight. Miami Cancer Institute, in concert with Florida International Universitys Herbert Wertheim College of Medicine, offers a two-year Urologic Oncology fellowship covering all treatment modalities.

We also work with Year 3 and 4 medical students who havent yet chosen a specialty. Its my job to introduce them to the challenges of our super-specialty and pique their interest in pursuing urologic oncological surgery.

Lastly, we support working physicians who desire to continue their education in the specialty. My colleagues and I offer surgical observation opportunities for local physicians as well as participate in international training programs.

The advent of teleconferencing has created exciting new training opportunities. We offer bimonthly telemedicine webinars through Baptist Urological Academy to an international audience. Many participating physicians and fellows become recognized urologic oncologists in their own countries.

Managing prostate cancer starts with screening and early diagnosis but extends into the effective management of prostate cancer. It requires constructive participation of all involved in the prostate cancer management including the government, health institutions, physicians, health care staff and most importantly, the patients.

REFERENCES

1, Siegel RL,Miller KD,Wagle, NS,and Jemal A, A.Cancer statistics, 2023.CA Cancer J Clin2023;73(1):17-48. doi:10.3322/caac.21763

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Rise in Prostate Cancer Cases Contributes to Challenges in Care - Targeted Oncology