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Mesenchymal stem cells: a beacon of hope for treating degenerative diseases and prolonging life
What are mesenchymal stem cells?
MSCs are multipotent stromal cells, which means they can differentiate into different cell types. Originating mainly from bone marrow, they can also be found in various other tissues such as fat, umbilical cord blood, dental pulp, etc. Unlike other stem cells, mesenchymal stem cells (MSCs) have a special detection principle immune system, which reduces the likelihood of rejection when transplanted into the recipient, making them stronger candidates for therapeutic use.
Therapeutic potential of degenerative diseases
Osteoarthritis: Osteoarthritis (OA), one of the most common degenerative joint diseases, destroys cartilage and leads to joint pain and stiffness. MSCs show promising efficacy in OA by promoting cartilage repair. When injected into an affected joint, these cells can promote cartilage regeneration, support pain reduction, and improve joint functionality. Spinal Cord Injuries: Traumatic injuries to the spinal cord can lead to paralysis and a variety of other conditions. In recent studies, MSCs have demonstrated the ability to deplete and stimulate neuronal growth, creating a favorable environment for spinal cord repair. Cardiovascular disease: After a heart attack, heart tissue may be permanently damaged. MSCs were studied for their ability to regenerate cardiac tissue. Their ability to differentiate into cardiomyocytes, combined with anti-inflammatory and angiogenic substances, makes them effective in the fight against heart disease. Neurodegenerative disease: Conditions such as Parkinson's and Alzheimer's diseases are characterized by the progressive degeneration of nerve cells. MSCs can provide a supportive environment, provide neuroprotection, and even replace lost cells, although research in this area is still in its early stages.
In addition to degenerative diseases, MSCs are of great importance in the field of longevity and anti-aging treatments. Aging is essentially a degenerative process characterized by cell destruction. Here’s how to awaken MSC:
Anti-inflammatory properties: Chronic nutrition plays a key role in aging. MSC uses effective anti-inflammatory mechanisms that can mitigate this process, ensuring a slowdown in the aging process at the cellular level. Tissue repair and regeneration: As we age, our body's ability to repair and regenerate declines. The introduction of MSCs can enhance these processes, rejuvenating tissues and possibly extending lifespan. Mitochondrial Support: Mitochondria, the powerhouses of our cells, deteriorate as we age. MSC can support mitochondrial health, causing cells to produce the energy needed to maintain resilience.
Mesenchymal stem cells, with their uniqueness and versatility, are currently leaders in regenerative medicine. Their potential for the future of degenerative diseases and longevity is enormous. However, it is important to approach their therapeutic use with cautious optimism. Although early results are promising, continued research is critical to fully exploit its potential and ensure patient safety. As science advances, MSC may well rewrite the history of aging and degeneration.
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Scientists Discover “Dynamite” Way To Wipe a Cell’s Memory To Better Reprogram It as a Stem Cell
Scientists have developed a revolutionary technique, termed “transient-naive-treatment (TNT) reprogramming.” This method allows human cells to be reprogrammed to more closely resemble embryonic stem cells, addressing a longstanding issue in regenerative medicine. The team’s breakthrough promises to set new standards for cell therapies and research. (Human iPS cells.)
A new method to reprogram human cells to better mimic embryonic stem cells.
In a groundbreaking study published on August 16 in the journal Nature, Australian scientists have resolved a long-standing problem in regenerative medicine. They developed a new method to reprogram human cells to better mimic embryonic stem cells, with significant implications for biomedical and therapeutic uses. The team of researchers was led by Professor Ryan Lister from the Harry Perkins Institute of Medical Research and The University of Western Australia and Professor Jose M Polo from Monash University and the University of Adelaide.
History and Challenges of Cell Reprogramming
In a revolutionary advance in the mid-2000s, it was discovered that the non-reproductive adult cells of the body, called ‘somatic’ cells, could be artificially reprogrammed into a state that resembles embryonic stem (ES) cells which have the capacity to then generate any cell of the body.
The transformative ability to artificially reprogram human somatic cells, such as skin cells, into these so-called induced pluripotent stem (iPS) cells provided a way to make an essentially unlimited supply of ES-like cells. This has widespread applications in disease modeling, drug screening, and cell-based therapies.
“However, a persistent problem with the conventional reprogramming process is that iPS cells can retain an epigenetic memory of their original somatic state, as well as other epigenetic abnormalities,” Professor Lister said. “This can create functional differences between the iPS cells and the ES cells they’re supposed to imitate, and specialized cells subsequently derived from them, which limits their use.”
Introducing the TNT Reprogramming Technique
Professor Jose Polo, who is also with the Monash Biomedicine Discovery Institute, explained that they have now developed a new method, called transient-naive-treatment (TNT) reprogramming, that mimics the reset of a cell’s epigenome that happens in very early embryonic development.
“This significantly reduces the differences between iPS cells and ES cells and maximizes the effectiveness of how human iPS cells can be applied,” he said.
Dr. Sam Buckberry, a computational scientist from the Harry Perkins Institute, UWA, and Telethon Kids Institute, and co-first author of the study, said by studying how the somatic cell epigenome changed throughout the reprogramming process, they pinpointed when epigenetic aberrations emerged, and introduced a new epigenome reset step to avoid them and erase the memory.
Dr. Xiaodong Liu, a stem cell scientist who also spearheaded the research said the new human TNT-iPS cells much more closely resembled human ES cells – both molecularly and functionally – than those produced using conventional reprogramming.
Improved Results With TNT Method
Dr. Daniel Poppe, a cell biologist from UWA, the Harry Perkins Institute, and co-first author, said the iPS cells generated using the TNT method differentiated into many other cells, such as neuron progenitors, better than the iPS cells generated with the standard method.
Monash University student and co-first author Jia Tan said the team’s TNT method was dynamite.
“It solves problems associated with conventionally generated iPS cells that if not addressed could have severely detrimental consequences for cell therapies in the long run,” he said.
Future Implications and Research
Professor Polo said that despite their breakthrough, the precise molecular mechanisms underlying the iPS epigenome aberrations and their correction are not fully known. Further research is needed to understand them.
Cornell Study Reveals Why Cancer May Spread to the Spine
Researchers at Weill Cornell Medicine found that the vertebral bones of the spine are formed from a unique stem cell type that releases a protein, MFGE8, promoting tumor metastasis. This discovery offers insights into spinal disorders, and reasons tumors often spread to the spine, and could pave the way for new treatments in orthopedics and oncology.
The spinal vertebral bones originate from a unique stem cell type that secretes a protein favoring tumor metastases, according to a study led by researchers at Weill Cornell Medicine. This breakthrough paves the way for a new line of research into spinal disorders, provides insights into why solid tumors frequently metastasize to the spine and could lead to new orthopedic and cancer treatments.
In the study, published Sept. 13 in Nature, the researchers discovered that vertebral bone is derived from a stem cell that is different from other bone-making stem cells. Using bone-like “organoids” made from vertebral stem cells, they showed that the known tendency of tumors to spread to the spine—more than to long bones such as leg bones—is due largely to a protein called MFGE8, secreted by these stem cells.
“We suspect that many bone diseases preferentially involving the spine are attributable to the distinct properties of vertebral bone stem cells,” said study senior author Dr. Matthew Greenblatt, an associate professor of pathology and laboratory medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center.
In recent years, Dr. Greenblatt and other scientists have found that different types of bone are derived from different types of bone stem cells. Since vertebrae, in comparison with other bones such as arm and leg bones, develop along a different pathway early in life, and also appear to have had a distinct evolutionary trajectory, Dr. Greenblatt and his team hypothesized that a distinct vertebral stem cell probably exists.
The researchers started out by isolating what are broadly known as skeletal stem cells, which give rise to all bone and cartilage, from different bones in lab mice based on known surface protein markers of such cells. They then analyzed gene activity in these cells to see if they could find a distinct pattern for the ones associated with vertebral bone.
This effort yielded two key findings. The first was a new and more accurate surface-marker-based definition of skeletal stem cells as a whole. This new definition excluded a set of cells that are not stem cells that had been included in the old stem cell definition, thus clouding some prior research in this area.
The second finding was that skeletal stem cells from different bones do indeed vary systematically in their gene activity. From this analysis, the team identified a distinct set of markers for vertebral stem cells and confirmed these cells’ functional roles in forming spinal bone in further experiments in mice and in lab-dish cell culture systems.
The researchers next investigated the phenomenon of the spine’s relative attraction for tumor metastases—including breast, prostate, and lung tumor metastases—compared to other types of bone. The traditional theory, dating to the 1940s, is that this “spinal tropism” relates to patterns of blood flow that preferentially convey metastases to the spine versus long bones. But when the researchers reproduced the spinal tropism phenomenon in animal models, they found evidence that blood flow isn’t the explanation—indeed, they found a clue pointing to vertebral stem cells as the possible culprits.
“We observed that the site of initial seeding of metastatic tumor cells was predominantly in an area of marrow where vertebral stem cells and their progeny cells would be located,” said study first author Dr. Jun Sun, a postdoctoral researcher in the Greenblatt laboratory.
Subsequently, the team found that removing vertebral stem cells eliminated the difference in metastasis rates between spine bones and long bones. Ultimately, they determined that MFGE8, a protein secreted in higher amounts by vertebral compared to long bone stem cells, is a major contributor to spinal tropism. To confirm the relevance of the findings in humans, the team collaborated with investigators at the Hospital for Special Surgery to identify the human counterparts of the mouse vertebral stem cells and characterize their properties.
The researchers are now exploring methods for blocking MFGE8 to reduce the risk of spinal metastasis in cancer patients. More generally, said Dr. Greenblatt, they are studying how the distinctive properties of vertebral stem cells contribute to spinal disorders.
“There’s a subdiscipline in orthopedics called spinal orthopedics, and we think that most of the conditions in that clinical category have to do with this stem cell we’ve just identified,” Dr. Greenblatt said.
Stem Cells From Discarded Heart Tissue Could Treat Crohn’s Disease
Scientists discovered that neonatal mesenchymal stem cells from discarded heart tissue can reduce intestinal inflammation and enhance wound healing in a mouse model of Crohn’s disease-like ileitis. The study offers a promising treatment alternative that avoids the drawbacks of current medications.
Research found decreased intestinal inflammation and improved wound healing in a mouse model.
A study from the Ann & Robert H. Lurie Children’s Hospital of Chicago discovered that directly injecting neonatal mesenchymal stem cells, sourced from heart tissue usually discarded during surgery, reduces intestinal inflammation and promotes wound healing in a mouse model of Crohn’s disease-like ileitis, an illness marked by chronic intestinal inflammation and progressive tissue damage.
The study, published in the journal Advanced Therapeutics, offers a promising new and alternative treatment approach that avoids the pitfalls of current Crohn’s disease medications, including diminishing effectiveness, severe side effects and increased risk of gastrointestinal dysfunction.
“Neonatal cardiac-derived mesenchymal stem cells have been used in a clinical trial to repair an injured heart, but this is the first time these potent cells have been studied in an inflammatory intestinal disease model,” said senior author Arun Sharma, PhD, from Stanley Manne Children’s Research Institute at Lurie Children’s who is the Director of Pediatric Urological Regenerative Medicine and Surgical Research, and Research Associate Professor of Urology and Biomedical Engineering at Northwestern University Feinberg School of Medicine and the McCormick School of Engineering, Northwestern University. “Our results are encouraging and definitely provide a new platform to potentially treat aspects of chronic inflammatory bowel diseases.”
Dr. Sharma explains that before it would be feasible to use these stem cells clinically to treat Crohn’s disease, his team needs to overcome the hurdle of how they are administered. In the current animal model study, the stem cells were injected directly into the inflammatory lesions in the small intestine, which requires surgical procedures. The next step then is to develop a safe way to inject them into the body through a vein, similar to performing a blood draw in the arm of a patient. More animal studies will be needed before this novel treatment approach can progress to clinical trials.
“Ultimately our goal is to utilize this cell type as treatment, but also as a preventive measure, before signs and symptoms of Crohn’s disease develop,” said Dr. Sharma. “We also might be able to apply this approach to other inflammatory diseases. The potential is enormous, and we are excited to move forward.”