Scientists have developed a genome editing system that has successfully modified the DNA of mice with a mutation similar to that found in people with autism spectrum disorder (ASD), writes SCMP.

The article says special mice were bred for research with a mutation in the MEF2C gene, which they say is “strongly associated” with the disorder. Thus, mutations in this gene cause developmental disorders, speech problems, repetitive behavior and epilepsy, rbc.ru reports.

The developed system for editing the MEF2C gene was called AeCBE. As the study authors note, mice that received a special injection showed a decrease in behavior associated with ASD. The scientists emphasized that the potential treatment could be used not only for patients with ASD, but also for other genetic neurodevelopmental disorders.

A professor at East China Normal University told SCMP that this is the first effective treatment for mice with mutations associated with ASD. The injection would go directly into the mouse’s brain, he said, so scientists needed to learn how to safely interact with the blood-brain barrier, a group of cells that regulate the entry of foreign molecules into the brain. By studying mouse brain cells, the researchers found that AeCBE was able to “make repairs” throughout the brain with about 20% accuracy, which was enough to boost MEF2C protein levels, SCMP writes. “The treatment successfully restored MEF2C protein levels in several brain regions and reversed behavioral abnormalities in mice with the MEF2C mutation,” the paper states.

The exact cause of ASD is still unknown, but it is believed that 80–90% of cases are due to genetic predisposition. More than 100 genes have already been found that scientists associate with the occurrence of autism. But there are also environmental factors that can also contribute to the development of this disorder in a child. For example, inflammation in the mother’s body during pregnancy has been linked to an increased risk of ASD in the child. It can occur due to chronic diseases: arthritis, lupus or diabetes, and can also be triggered by obesity due to cytokines that penetrate the blood-brain barrier and attack neural networks.

Some people diagnosed with ASD as children outgrow it, achieving an “optimal outcome.” The term was coined by Deborah Fine, a professor of psychology at the University of Connecticut in Storrs. In 2013, she conducted research with 34 people diagnosed with autism. In 2016, scientists reviewed cases of “optimal outcomes” and concluded that it is possible to talk about loss of diagnosis only if it is made early. Timely, intensive behavioral intervention plays an equally important role. A large proportion of people with autism maintain symptoms consistent with the diagnosis and require therapy and support throughout their lives.

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.

Longevity treatment

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.

Finally

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.

The manufacturers of 10 medicines for serious illnesses, selected earlier in the year for price negotiations with the US government, have all agreed to participate in the talks, the White House said Tuesday.

Emily Gebel was trying to figure out why she was having trouble breastfeeding. That’s when she felt a lump.

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.

Source: SciTechDaily

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.

Source: SciTechDaily