Researchers have uncovered significant changes in chromosome structure and gene expression that influence stem cell function during aging. Their study, conducted using fruit flies and published in iScience on September 9, reveals that these changes result in stem cell exhaustion, a state where stem cells lose their ability to multiply. This groundbreaking discovery provides the first evidence of an independent exhaustion signal and offers new insights into how the balance between stem cell exhaustion and proliferation is disrupted during the aging process.

In healthy organs such as the kidneys or intestines, stem cells respond to damage by multiplying and transforming into the specific cell types needed for repair and regeneration. However, as animals, including humans, age, this regenerative process can become impaired.

Sometimes, stem cells may divide uncontrollably, leading to excessive numbers that can result in cancer. Conversely, they may become depleted and lose their ability to divide, hindering tissue repair—a condition known as stem cell exhaustion.

While the mechanisms of stem cell proliferation are relatively well-understood in humans, the causes of exhaustion remain largely unexplored.

Previously, Sa Kan Yoo and his team at RIKEN BDR discovered how aging can cause intestinal stem cells in fruit flies to become cancerous. Building on this work, the researchers explored whether a mechanism independent of proliferation could also drive stem cell exhaustion.

Using fruit flies as a model, they analyzed the chromatin structure in intestinal stem cells and identified a specific region of chromatin that tends to close during aging. This closure prevents the production of a key regulator encoded in this DNA region. One of the genes affected by this regulator is ced-6, whose expression they evaluated using RNA sequencing.

Their findings revealed that ced-6 expression decreases with age. To investigate its role in stem cell exhaustion, the researchers blocked ced-6 expression, which stopped age-related stem cell proliferation, confirming that this gene helps prevent stem cell exhaustion.

Interestingly, they also found that blocking ced-6 could induce stem cell exhaustion at any age. When intestinal cells were damaged, stem cells typically proliferated, differentiated, and repaired the tissue. However, when ced-6 was blocked in damaged intestinal cells, the stem cells failed to proliferate, leaving the tissue unrepaired.

These findings suggest that the exhaustion triggered by blocking ced-6 or other genes regulated by the same chromatin region is not restricted to advanced age. Instead, it appears to be a general mechanism that helps maintain balance when stem cell proliferation becomes excessive.

“Our study opens the door to significant advancements in aging research,” says Sa Kan Yoo. “By uncovering the mechanisms of stem cell exhaustion in fruit flies, we gain valuable insights into the broader aging process. This research could also provide important clues about how aging affects stem cells in humans. The next step is to investigate whether similar changes occur in human stem cells as they age.”

Older studies have found that the lifetime risk of developing symptomatic knee osteoarthritis is about 40% in men and 47% in women.”

Knee osteoarthritis occurs when the cartilage in one’s knee breaks down, causing the joint’s bones to rub directly together, creating friction.

The reduction in physical activity that may occur as a result of pain can lead to other health issues such as obesity, diabetes, and cardiovascular disease.

Some causes of knee osteoarthritis include:

• joint injuries, fractures, strains, and repeated stress on the joint
• joint diseases
• metabolic diseases, such as diabetes
• obesity, causing the joint to carry excess weight, as well as systemic inflammation, and metabolic issues
• sex — women develop osteoarthritis more often than men
• genetics

Regenerative medicine for the knee

Regenerative medicine for the knee is not something new, it includes stem cell therapy as well as injections of platelet-rich plasma.

This particular study focuses on the newer treatment of mesenchymal stem cell therapy as a treatment for knee osteoarthritis. Mesenchymal stem cells may be bone-marrow-derived, derived from adipose tissue (from fat), or umbilical-cord derived.”

Mesenchymal cells are stem cells that can develop into many types of connective tissue. They have large nuclei and are spindle-shaped.

Although there are studies evaluating various stem cells and comparing these treatments to platelet-rich plasma, few studies directly compare different types of stem cells for the treatment of knee osteoarthritis.

This study provides a systematic review comparison of the different types of stem cell therapies and their overall effectiveness on alleviating knee joint pain, restoring knee joint function, and minimizing knee joint trauma.

What would happen after a stem cell treatment?

Stem cell implantation may potentially repair affected tissue, develop new cartilage, decrease inflammation, and slow down further degeneration, this leads to decreased pain and improved functionality, which can contribute to joint strengthening.

The studies and meta-analysis use several scoring systems for assessing individuals’ pain levels.

As patient pain scores are improved restoration of function, including increased mobility/movement and subsequent strengthening and flexibility will follow. This allows for return to activities of daily living and enhanced well-being.”

Exercise is appropriate and will likely be encouraged with stem cell implants.

Early signs of cerebral palsy may include:

Developmental delays – The child may be slow to reach milestones like rolling over, sitting up, crawling, and walking. These delays are often the first indication of cerebral palsy.

Abnormal muscle tone – The child may have muscles that are either too stiff or too loose.

Abnormal posture – The child may show a preference for using one side of the body more than the other when reaching, crawling, or moving.

It’s important to note that some children without cerebral palsy might display these signs as well. If you notice any of these symptoms, it’s a good idea to consult with your child’s healthcare provider.

Age-Specific Signs:

Infants younger than 6 months may:

• Struggle to lift their head when picked up from a lying position.
• Feel stiff or floppy.
• Have stiff or crossed legs when picked up.
• Arch their back and neck when held, as though pushing away from you.

Infants older than 6 months may:

• Be unable to roll over.
• Struggle to bring their hands to their mouth.
• Have difficulty bringing their hands together.
• Reach with only one hand while keeping the other hand in a fist.

Infants older than 10 months may:

• Crawl unevenly, using one hand and leg to push while dragging the opposite limbs.
• Scoot on their buttocks or hop on their knees but not crawl on all fours.
• Be unable to stand, even when holding onto support.

If you observe any of these signs in your child, it’s important to discuss your concerns with a healthcare provider, as early intervention can make a significant difference.

Scientists from the University of Cambridge, University of Milan Bicocca, and Hospital Casa Sollievo della Sofferenza (Italy) have spearheaded a study aimed at advancing stem cell therapy for progressive multiple sclerosis. This research marks a significant milestone in the development of innovative therapies for this debilitating condition.

Over 2 million people live with MS worldwide, and while treatments exist that can reduce the severity and frequency of relapses, two-thirds of MS patients still transition into a debilitating secondary progressive phase of disease within 25-30 years of diagnosis, where disability grows steadily worse.

In MS, the body’s own immune system attacks and damages myelin, the protective sheath around nerve fibres, disrupting messages sent around the brain and spinal cord.

Key immune cells involved in this process are macrophages (literally ‘big eaters’), which ordinarily attack and rid the body of unwanted intruders. A particular type of macrophage known as a microglial cell is found throughout the brain and spinal cord. In progressive forms of MS, they attack the central nervous system (CNS), causing chronic inflammation and damage to nerve cells.

Recent advances have raised expectations that stem cell therapies might help ameliorate this damage. These involve the transplantation of stem cells, the body’s ‘master cells’, which can be programmed to develop into almost any type of cell within the body.

Previous work from the Cambridge team has shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, can help reduce inflammation and may be able to help repair damage caused by MS.

Now, in research published in the Cell Stem Cell, scientists have completed a first-in-man, early-stage clinical trial that involved injecting neural stem cells directly into the brains of 15 patients with secondary MS recruited from two hospitals in Italy.

The stem cells were derived from cells taken from brain tissue from a single, miscarried fetal donor. The Italian team had previously shown that it would be possible to produce a virtually limitless supply of these stem cells from a single donor — and in future it may be possible to derive these cells directly from the patient — helping to overcome practical problems associated with the use of allogeneic fetal tissue.

The team followed the patients over 12 months, during which time they observed no treatment-related deaths or serious adverse events. While some side-effects were observed, all were either temporary or reversible.

All the patients showed high levels of disability at the start of the trial — most required a wheelchair, for example — but during the 12-month follow-up period none showed any increase in disability or a worsening of symptoms. None of the patients reported symptoms that suggested a relapse and nor did their cognitive function worsen significantly during the study. Overall, say the researchers, this points to a substantial stability of the disease, without signs of progression, though the high levels of disability at the start of the trial make this difficult to confirm.

The researchers assessed a subgroup of patients for changes in the volume of brain tissue associated with disease progression. They found that the larger the dose of injected stem cells, the smaller the reduction in this brain volume over time. They speculate that this may be because the stem cell transplant dampened inflammation.

The team also looked for signs that the stem cells were having a neuroprotective effect — that is, protecting nerve cells from further damage. Their previous work showed how tweaking metabolism — how the body produces energy — can in turn reprogram microglia from ‘bad’ to ‘good’. In this new study, they looked at how the brain’s metabolism changes after the treatment. They measured changes in the fluid around the brain and in the blood over time and found certain signs that are linked to how the brain processes fatty acids. These signs were connected to how well the treatment works and how the disease develops. The higher the dose of stem cells, the greater the levels of fatty acids, which also persisted over the 12-month period.

Professor Stefano Pluchino from the University of Cambridge, who co-led the study, said: “We desperately need to develop new treatments for secondary progressive MS, and I am cautiously very excited about our findings, which are a step towards developing a cell therapy for treating MS.

“We recognize that our study has limitations — it was only a small study and there may have been confounding effects from the immunosuppressant drugs, for example — but the fact that our treatment was safe and that its effects lasted over the 12 months of the trial means that we can proceed to the next stage of clinical trials.”

Co-leader Professor Angelo Vescovi from the University of Milano-Bicocca said: “It has taken nearly three decades to translate the discovery of brain stem cells into this experimental therapeutic treatment This study will add to the increasing excitement in this field and pave the way to broader efficacy studies, soon to come.”

Caitlin Astbury, Research Communications Manager at the MS Society, says: “This is a really exciting study which builds on previous research funded by us. These results show that special stem cells injected into the brain were safe and well-tolerated by people with secondary progressive MS. They also suggest this treatment approach might even stabilize disability progression. We’ve known for some time that this method has the potential to help protect the brain from the progression in MS.

“This was a very small, early-stage study and we need further clinical trials to find out if this treatment has a beneficial effect on the condition. But this is an encouraging step towards a new way of treating some people with MS.”

Recently, Vertex Pharmaceuticals (VRTX.US) announced the latest data from the phase 1/2 clinical trial of its diabetes stem cell therapy VX-880 at the American Diabetes Association Annual Scientific Meeting (ADA): More than a year later, the two patients with type I diabetes no longer need insulin injections, and their diabetes-related symptoms and biochemical indicators have been significantly improved.

This is a Phase 1/2, multicenter, single-arm, open-label study in patients with type 1 diabetes (T1D), demonstrating the potential of stem cell-derived islet cell therapy as a future treatment option for patients with type 1 diabetes.

This study focused on adults with type I diabetes who had impaired hypoglycemia awareness and severe hypoglycemia. All six patients treated with VX-880 had undetectable insulin secretion and recurrent severe hypoglycemia in the year prior to treatment. History of the incident.

After treatment, all patients showed restoration of insulin secretion, improved glycemic control, reduction or elimination of exogenous insulin use, and a complete absence of severe hypoglycemic events during the 90-day evaluation period, the ADA said.

“These new findings demonstrate the potential of stem cell-derived islets as a future treatment for patients with type 1 diabetes and mark a new era that may eliminate the need for external source of insulin to achieve glycemic control.”

Currently, this research has been extended to Norway, Switzerland and the Netherlands. Further data on this therapy are still worth looking forward to.

Diabetes: nearly 600 million patients worldwide, it is urgent to explore new treatments

Diabetes is a multifactorial metabolic chronic disease characterized by chronic elevation of blood glucose caused by disorders of insulin secretion or function. Diabetes can cause serious complications in most systems and organs of the body, leading to disability, paralysis, and even death. The current treatment options for diabetes are mainly diet control, drug treatment or insulin treatment. These treatments cannot achieve a curative effect and may also have some side effects. In addition, the treatment of diabetes complications imposes a heavy economic burden on society.

Top 10 countries or regions with the number of adults with diabetes in 2021 and 2045 (Source: “2021 IDF Global Diabetes Map (10th Edition)”)

A recent study published in The Lancet [3] pointed out that there are currently 529 million diabetic patients in the world, and this number is expected to grow to 1.3 billion by 2050. The “Diabetes Atlas (10th Edition)” released by the World Health Organization in 2021 shows that China is the country with the largest number of adult patients with diabetes. The number of people with diabetes in China in 2021 is about 140 million, and it is expected to reach 174 million in 2045. This suggests that there is an urgent need to explore suitable alternative treatments.

The efficacy and progress of stem cell therapy in treating diabetes

Stem cells are a renewable source of cells considered an alternative to organ transplants, with their ability to divide and transform into highly differentiated cells to replace injured and dead cells. Most scientists have long considered the possibility of using stem cells to treat diabetes and create insulin islets, which could be a hope for controlling diabetes in the future. The table lists some studies on the role, challenges and progress of stem cells in diabetes treatment [2].

Here are several clinical efficacy cases of stem cell treatment for diabetes:

Stem cells help patients with type 1 diabetes become insulin-free [4]: This study enrolled a total of 53 participants, 33 with adult-onset and 20 with adolescent-onset type 1 diabetes (T1D).

Divided into stem cell treatment group and mesenchymal stem cell treatment group, this group was followed up for 1 year after intervention. It was found that 40.7% of the subjects in the mesenchymal stem cell treatment group had significant relief of clinical symptoms, and 3 subjects maintained their symptoms for 3 to 12 months. Insulin-free state, which was not present in the control group.

In adult-onset T1D, the percentage change in postprandial C-peptide levels was significantly higher in the mesenchymal stem cell-treated group than in the control group. The above follow-up results show the significant efficacy of stem cells in treating T1D, and no serious side effects were observed during treatment and follow-up.

Stem cell treatment of type 2 diabetes [5]: Chinese researchers published the results of a phase II clinical trial on the efficacy and safety of mesenchymal stem cells in the treatment of type 2 diabetes in Chinese adults in the journal Stem Cell Research & Therapy. This study included a total of 91 patients with type 2 diabetes (T2D), who were divided into a mesenchymal stem cell treatment group and a placebo group, and were followed up for 48 weeks.

The results found that 20% of patients in the mesenchymal stem cell treatment group had glycated hemoglobin (HbA1c) levels <7.0%, and the daily insulin dosage was reduced by more than half. In addition, the mesenchymal stem cell treatment group’s HbA1c level decreased by 1.31%.

Compared with the placebo group, only 4.55% of patients in the placebo group achieved HbA1c <7.0%, and the overall HbA1c only decreased by 0.63%. In summary, mesenchymal stem cell therapy significantly improved T2D, and there were no related adverse reactions during treatment and follow-up.

Stem cell treatment of diabetic foot ulcers [6]: Studies have shown that adipose tissue stem cells migrate to blood vessels at the site of leg injuries and wounds in diabetic patients, and then have multiple effects such as creating angiogenesis, preventing tissue fibrosis and increasing oxygen supply to the injured site. To repair tissue and thereby repair diabetic foot ulcers.

Challenges faced by stem cells in treating diabetes: The above data allow us to see the hope of stem cells in treating diabetes and provide an ideal treatment method for diabetic patients. However, when reaping the therapeutic effects, we also need to face up to the challenges brought by stem cell therapy.

These challenges include:

1. Improving the functions of produced stem cells to prevent excessive proliferation and potential teratoma formation, while ensuring proper differentiation and functionality, such as insulin secretion in derived islet cells.
2. Addressing immune rejection, reducing stress reactions, and enhancing graft survival rates post-transplantation.
3. Resolving ethical issues related to stem cell therapy and pursuing further advancements.

Summary

To sum up, stem cells, as an emerging disease treatment method, also show great potential in treating diabetes. Although the use of stem cell replacement methods to treat diabetes faces many challenges, I believe that with the continuous improvement of technology, in the future development, a cure for diabetes will no longer be out of reach.

References：

1. https://www.statnews.com/2023/06/23/vertex-diabetes-cell-therapy-insulin/
2. Farzaneh Fazeli; Masumeh Ahanjan. “The capacity of stem cells in treatment of diabetes”.Cellular, Molecular and Biomedical Reports, 2, 4, 2022, 230-244. doi: 10.55705/cmbr.2022.357066.1060
3. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023 Jul 15;402(10397):203-234. doi: 10.1016/S0140-6736(23)01301-6. Epub 2023 Jun 22. Erratum in: Lancet. 2023 Sep 30;402(10408):1132.
4. Lu J, Shen SM, Ling Q, Wang B, Li LR, Zhang W, Qu DD, Bi Y, Zhu DL. One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study. Stem Cell Res Ther. 2021 Jun 10;12(1):340. doi: 10.1186/s13287-021-02417-
5. Li Zang, et al. Efficacy and safety of umbilical cord derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single center, double blinded, randomized, placebo controlled phase II trial. Stem Cell Res Ther. 2022, 13 (1):180.
6. Lopes L, Setia O, Aurshina A, Liu S, Hu H, Isaji T, Liu H, Wang T, Ono S, Guo X (2018) Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research. Stem cell research & therapy 9 (1): 1-16.

Two of the most common forms of COPD are chronic bronchitis and emphysema.

The most prevalent symptoms of COPD are shortness of breath and a cough. Over time, even everyday activities, such as getting dressed, can become challenging.

1. COPD is rare

According to the World Health Organization (WHO), COPD caused 3.23 million deaths in 2019, making it the third leading cause of death worldwide.

In the United States, COPD “is the fourth leading cause of death. More than 16 million Americans are diagnosed, and millions more people may be undiagnosed.”

The American Lung Association (ALA) recommends that anyone who is “experiencing COPD symptoms — chronic cough, shortness of breath, frequent respiratory infections, significant mucus production (also called phlegm or sputum), and/or wheezing — speak with [a] doctor about obtaining a breathing test called ‘spirometry,’ which can help diagnose COPD.”

2. Only smokers develop COPD

It is true that smoking tobacco is the leading cause of COPD, but as Dr. Schachter told MNT, “There are many other risk factors that contribute to the development of the disease, including air pollution, work-related pollution, infection, and some forms of asthma.”

Approximately 10–20% of COPD patients never smoked. Some of these never-smokers include significant secondhand smoke exposure; genetic predisposition, primarily through alpha-1 antitrypsin deficiency; or substantial exposure to air pollution.

Alpha-1 antitrypsin is an enzyme that protects the body from an immune attack. Some people have a mutation in the gene that codes for this enzyme; this causes alpha-1 antitrypsin deficiency.

Deficiency of alpha-1 antitrypsin increases the risk of developing COPD and other conditions that affect a range of bodily systems.

3. Only older adults develop COPD

COPD is certainly more common in older adults than in younger people, but younger people are not immune to the condition.

For instance, in the U.S., between 2007 and 2009, COPD affected 2% of males and 4.1% of females aged 24–44 years. Similarly, the condition affected 2% of males and 3% of females aged 18–24 years.

A significant proportion of those individuals diagnosed before the age of 50 have a hereditary form of the disease that causes a deficiency of alpha-1 antitrypsin.

4. COPD only affects the lungs

“False,” said Dr. Schachter. “COPD coexists with many comorbidities, including heart disease, lung cancer, hypertension, osteoporosis, and diabetes. The association may be due to common causative factors, as well as ‘systemic inflammation.’”

In other words, some of these conditions share risk factors, which makes them more likely to occur with COPD. For instance, smoking is a risk factor for both COPD and heart disease.

At the same time, health experts associate COPD with systemic inflammation, which can also independently increase the risk of other conditions.

5. People with COPD cannot exercise

According to Dr. Yadegar, “Without proper guidance, patients with COPD may have difficulty completing physical exercises.”

However, he also explained that doctors recommend people with COPD do exercise, as it can help “increase their breathing capacity and improve their daily symptoms.”

“Pulmonary rehabilitation programs typically offer guided breathing techniques in conjunction with physical exercise in order to maximize better patient outcomes,” he continued.

In a nutshell, Dr. Schachter told us that “exercise is therapeutic for COPD, reducing the number of exacerbations and improving quality of life.”

The ALA notes:

“You might feel like it is not safe or even possible to exercise, but the right amount and type of exercise has many benefits. Be sure to ask your doctor before you start or make changes to your exercise routine.”

6. There are no treatments for COPD

This, thankfully, is a myth. “There are numerous therapies and strategies that improve the course of the disease,” Dr. Schachter told MNT, “including medications, rehabilitation, diet, and vaccines that protect against respiratory infections that accelerate the course of the disease.”

Dr. Yadegar said, “With a spectrum of presentations, patients may benefit from inhaled bronchodilators, anticholinergics, corticosteroids, and supplemental oxygen.” These, he said, can be tailored uniquely to each person.

“Certain patients may also benefit from alpha-1 antitrypsin augmentation or even lung transplants,” he added.

7. COPD is the same as asthma

“While both diseases are considered obstructive lung diseases, there are several differences between COPD and asthma,” Dr. Yadegar explained.

“Asthma most commonly begins in childhood, where it is frequently associated with allergies and problems of inflammation. COPD usually begins in the 60s and is associated with smoking. There is, however, an overlap syndrome, which has features of both.”

– Dr. Neil Schachter

Dr. Yadegar dove into the details: “COPD is a disease of the alveoli, mostly […] a result of elasticity loss induced primarily by smoking. Asthma is a disease of the airways, primarily […] a result of chronic airway inflammation.”

“While clinical symptoms may overlap between the two diseases,” he continued, “treatments vary in order to best help patients in the short and long term.”

8. Body weight does not affect COPD

This is not true. Dr. Schachter told us that carrying excess body weight can increase the disability associated with COPD.

Conversely, if people have a body weight that is below moderate, it can be “a sign of emphysema and also indicates a poor prognosis.”

9. If you have COPD, there is no point quitting smoking

This is another myth. As Dr. Schachter told MNT, “It is never too late to quit.”

He explained that “smoking accelerates the loss of lung function that accompanies COPD.” He also said that smoking tobacco can promote exacerbations of the symptoms.

10. Shortness of breath is the only symptom of COPD

“Shortness of breath is a major presenting symptom but hardly the only one,” according to Dr. Schachter.

“Cough, excess phlegm production, respiratory infections, and all the symptoms of the comorbidities are often signs of progressing COPD.”

Other symptoms can include sleep problems, anxiety, depression, pain, and cognitive decline.

11. A healthy diet cannot help with COPD

As a matter of fact, a healthy diet can make a difference for people living with COPD. Dr. Schachter told MNT that a healthy diet promotes “general health and can protect against exacerbations of COPD itself and its comorbidities.”

For example, a 2020 meta-analysis of eight observational studies investigated the role of diet in COPD. The authors conclude that “healthy dietary patterns are associated with a lower prevalence of COPD, while unhealthy dietary patterns are not.”

Similarly, the data generated in another review suggest that “a higher intake of fruits, probably dietary fiber, and fish reduce the risk of COPD.”

In summary, although there is no cure for COPD, treatments are available, and lifestyle changes can reduce symptom severity.

Chronic diseases are diseases that result from the combined effects of multiple factors, such as genetics, physiology, environment, and behavior. They are responsible for 41 million deaths per year, accounting for 71% of global deaths. Among them, the elderly population is highly susceptible to chronic diseases. According to data from the National Health Commission of China, more than 260 million middle-aged and elderly people in China suffer from chronic diseases, and this number continues to rise. Therefore, chronic diseases are considered a major cause of global mortality and disability, and they are recognized as one of the key health challenges of the 21st century.

The common chronic diseases include cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases. Cardiovascular diseases encompass conditions such as hypertension, stroke, and coronary artery disease (coronary heart disease). Chronic diseases, being lifelong conditions, pose a significant public health challenge that impacts social and economic development. They have become the leading burden of disease worldwide.

Decades of research on mesenchymal stem cells in the treatment of chronic diseases

In recent years, stem cells have been widely applied in clinical research for the treatment of common chronic diseases. As early as 2014, researchers from the Stem Cell Laboratory at the University of Milan published a review article titled “Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases“. The article suggests that utilizing stem cell technology for intervention in the treatment and management of chronic diseases in the middle-aged and elderly population holds significant importance in curing diseases and improving quality of life.

MSCs have the potential to differentiate into various tissues of mesodermal origin, can be isolated from multiple tissues, and have the ability to expand in vitro. In addition, MSCs have been shown to produce anti-inflammatory molecules that modulate the cellular immune response.

Therefore, in the past two decades, research on MSCs has increased significantly, gradually becoming more in-depth and leading to significant progress in understanding the key characteristics of MSCs. This progress has provided valuable experience for the development of rational cell therapy strategies, and MSC-based approaches have played a positive role in clinical research on chronic diseases.

Case studies of mesenchymal stem cells in the treatment of chronic diseases

Here is a list of clinical advancements in stem cell therapy for the treatment of some common chronic diseases, providing a better understanding of the advantages of stem cell therapy in managing these conditions:

1. Type 1 Diabetes

Type 1 diabetes is an autoimmune disease in which the 𝛽-pancreatic cells are destroyed, leading to insufficient insulin production to control blood sugar levels. Despite exogenous insulin administration, chronic hyperglycemia can result in vascular degeneration, blindness, and kidney failure.

Mesenchymal stem cells have immunomodulatory properties and are a promising immune therapy for type 1 diabetes. As of now, dozens of clinical trials involving mesenchymal stem cell therapy for type 1 diabetes are registered on www.clinicaltrials.gov.

Researchers in China have also published clinical research findings in this field. For example, the Endocrinology Department of Drum Tower Hospital, Nanjing University Medical School, conducted a non-randomized, open-label, parallel-controlled clinical study. They administered mesenchymal stem cells at a dose of 10^6/kg to 53 patients with type 1 diabetes, followed by a second infusion after 3 months. After a 1-year follow-up, they observed a complete remission rate of 40.7% among the patients, and no severe adverse reactions related to the transplantation were observed.

2. Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any part of the body. The findings suggest that there are some defects in the hematopoietic system of SLE patients, possibly due to the unbalanced expression of cytokines and other growth factors.

A large number of clinical studies have been carried out in China on the treatment of SLE with mesenchymal stem cells, and the results have been published. In 2017, the Department of Dermatology of the Second Affiliated Hospital of Kunming Medical University conducted a prospective, randomized, double-blind clinical study in which 108 SLE patients were infused with mesenchymal stem cells for treatment. Clinical results showed improvements in patient’s renal function, and decreased proteinuria, while serum albumin increased. At the same time, other measures of SLE also improved.

In 2014, Drum Tower Hospital Affiliated to Nanjing University School of Medicine conducted a clinical trial on 40 patients with active and refractory SLE. After mesenchymal stem cell infusion treatment, the patient’s observations showed a significant decrease in SLEDAI and BILAG scores, as well as proteinuria, serum creatinine, and blood urea nitrogen. Concurrently, serum albumin and complement concentrations increased, and no administration-related adverse events were shown, and the intervention was well tolerated by all participants.

In 2019, the Ministry of Science and Technology awarded the “Second Prize of National Technology Invention Award” to an academic team headed by Professor Sun Lingyun who has made outstanding contributions in the field of mesenchymal stem cell therapy for SLE, bringing stem cell therapy into the public eye.

In 2022, a consensus was reached by numerous experts in the field of rheumatology and immunology in China on the use of allogeneic mesenchymal stem cell therapy for SLE) This consensus, titled “Expert Consensus on Allogeneic Mesenchymal Stem Cell Therapy for Systemic Lupus Erythematosus,” provides solid support for the application of mesenchymal stem cells in treating SLE. The consensus clearly states that more than 1,500 SLE patients worldwide have received mesenchymal stem cell therapy. This treatment has significantly improved the efficacy, overall quality of life, and prognosis of patients with SLE.

3. Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic joint inflammation due to loss of immune self-tolerance, characterized by joint inflammation, synovial hyperplasia, and progressive joint damage, cartilage and bone destruction, and over time Gradually worsened.

Studies have shown that mesenchymal stem cells can regulate their local environment, activate endogenous progenitor cells through intercellular interactions and secretion of various factors, and play a role in tissue damage repair. Mesenchymal stem cells can also produce a variety of growth factors and cytokines, which play an important role in tissue repair and remodeling. These properties make mesenchymal stem cells clinically promising for the treatment of rheumatoid arthritis.

Researchers at the Army Medical University published their findings in the Rheumatic Immunology Journal Annals of Rheumatology. Compared with conventional mesenchymal stem cell transplantation therapy, the effective rate of mesenchymal stem cell therapy for rheumatoid arthritis has increased by 40%, which can be described as an important advancement in the field of mesenchymal stem cell therapy for rheumatoid arthritis.

4. Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons (DA). Intermediate dopaminergic pathways project in the striatum, and their loss results in severe motor complications including rigidity, bradykinesia, and postural instability.

DA agonists and levodopa are effective symptomatic treatments, but unfortunately, with long-term use, they become ineffective and patients experience severe side effects. Stem cell therapy is therefore the most promising strategy for controlling this disease, by replacing lost neurons.

A clinical study took place in China included 26 patients with Parkinson’s disease, and transplanted mesenchymal stem cells into the posterior cerebral artery and superior cerebellar artery via catheter. It was found that after the transplantation, the patient’s disease score decreased significantly, and there was no adverse effect on liver and kidney function and no adverse reactions such as fever. This clinical study affirmed the role of mesenchymal stem cells, indicating that its treatment of Parkinson’s disease can significantly improve patients’ daily activities and motor function, without side effects, safe and reliable.

In addition to the chronic diseases mentioned above, literature also indicates promising clinical progress of mesenchymal stem cells in common chronic diseases such as musculoskeletal disorders, Alzheimer’s disease, cardiovascular diseases, liver diseases, and neurodegenerative diseases. However, further randomized, controlled, multicenter clinical trials are still needed to investigate the safety, quality control, clinical-grade production, clinical translation, and optimal conditions for MSC therapy. With the continued expansion of clinical research, it is believed that MSCs will benefit more patients with chronic diseases.

References

[1] Recreational football is medicine against non‐communicable diseases: A systematic review

https://pubmed.ncbi.nlm.nih.gov/31834941/

[2] Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases

https://pubmed.ncbi.nlm.nih.gov/24876848/

[3]https://stemcellsportal.com/news/stem-cell-based-implants-successfully-secrete-insulin-patients-type-1-diabetes

[4] One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study.

https://pubmed.ncbi.nlm.nih.gov/34112266/

[5] A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis.

https://pubmed.ncbi.nlm.nih.gov/28478399/

[6] Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study.

https://pubmed.ncbi.nlm.nih.gov/24661633/

[7] Zhao C, Zhang L, Kong W, Liang J, Xu XY, Wu HY, Feng XB, Hua BZ, Wang H, Sun LY: Umbilical Cord-Derived Mesenchymal Stem Cells Inhibit Cadherin-11 Expression by Fibroblast-Like Synoviocytes in Rheumatoid Arthritis. J Immunol Res 2015.

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Duchenne muscular dystrophy (DMD) is a rare and life-limiting genetic condition primarily observed in boys. It is characterized by progressive muscle weakness, which typically begins in early childhood. There is no cure at the moment.

The trial will recruit 10 boys under four years of age worldwide, with patients followed over a period of at least five years to measure the therapy’s effectiveness, including three in NSW who are being treated at The Children’s Hospital at Westmead.

The DMD clinical trial will use a novel viral vector-based gene replacement therapy to target DMD at its root cause, replacing the faulty or mutated gene with a healthy version in a single-dose infusion.

Current management of DMD involves high-dosed steroids, combined with physical therapy and allied health support but while it can lead to some improvement, it is also associated with difficult side effects and is not a long-term treatment.

Gene replacement therapy has already shown success in treating other genetic conditions, including spinal muscular atrophy (SMA), a condition causing rapidly progressive muscle weakness and early death in children.

The DMD clinical trial was enabled by the Kids Advanced Therapeutics Program at SCHN, a program kindly supported by Luminesce Alliance and Sydney Children’s Hospitals Foundation which aims to deliver clinical trials of advanced therapeutics and to speed up translation into clinical care.

Right now, there’s no cure for the disease. But there are many treatments that can improve symptoms and make life easier for you and your child.

Your doctor will recommend a treatment based on the type of muscular dystrophy your child has. Some of them are:

• Physical therapy uses different exercises and stretches to keep muscles strong and flexible.
• Occupational therapy teaches your child how to make the most of what their muscles can do. Therapists can also show them how to use wheelchairs, braces, and other devices that can help them with daily life.
• Speech therapy will teach them easier ways to talk if their throat or face muscles are weak.
  Respiratory therapy can help if your child is having trouble breathing. They’ll learn ways to make it easier to breathe, or get machines to help.
• Medicines can help ease symptoms. They include:
  • Eteplirsen (Exondys 51), golodirsen (Vyondys53), and vitolarsen (Viltepso) for treating DMD. They are injection medications that help treat individuals with a specific mutation of the gene that leads to DMD, specifically by increasing dystrophin production. Talk to your child’s doctor about possible side effects.
  • Anti-seizure drugs that reduce muscle spasms.
  • Blood pressure medicines that help with heart problems.
  • Drugs that turn down the body’s immune system, called immunosuppressants; they may slow damage to muscle cells.
  • Steroids like prednisone and defkazacort (Emflaza) that slow down muscle damage and can help your child breathe better. They can cause serious side effects, such as weak bones and a higher risk of infections.
  • Creatine, a chemical normally found in the body, that can help supply energy to muscles and improve strength for some people. Ask your child’s doctor if these supplements are a good idea for them.
• Surgery can help with different complications of muscular dystrophy, like heart problems or trouble swallowing.

Scientists also are looking for new ways to treat muscular dystrophy in clinical trials. These trials test new drugs to see if they are safe and if they work. They often are a way for people to try new medicine that isn’t available to everyone. Your doctor can tell you if one of these trials might be a good fit for your child.

Taking Care of Your Child

It’s hard when your child loses strength and can’t do the things other kids can do. Muscular dystrophy is a challenge, but it doesn’t have to keep your child from enjoying life.

There are many things you can do to help them feel stronger and get the most out of life.

• Eat right. A healthy, well-balanced diet is good for your child in general. It’s also important for helping them stay at a healthy weight, which can ease breathing problems and other symptoms. If it’s hard for them to chew or swallow, talk to a dietitian about foods that may be easier to eat.
• Stay active. Exercise can improve your child’s muscle strength and make them feel better. Try low-impact activities like swimming.
• Get enough sleep. Ask your doctor or therapist about certain beds or pads that can make your child more comfortable and rested.
• Use the right tools. Wheelchairs, crutches, or electric scooters can help your child if they have trouble walking.

The disease will most likely have a big impact on your family. Remember that it’s OK to ask a doctor, counselor, family, or friends for help with any stress, sadness, or anger you may feel. Support groups are also good places to talk to other people who have lived with muscular dystrophy. They can help your child connect with others like them and give you and your family advice and understanding.

Getting a Diagnosis

Your doctor will need to check different parts of your child’s body to know if they have muscular dystrophy. They’ll start with a general physical exam. They’ll also ask you questions about your family’s medical history and the kind of symptoms you’re noticing in your child. They may ask:

• Which muscles seem to be giving them trouble?
• Do they have a hard time walking or doing their usual activities?
• How long has this been happening?
• Does anyone in your family have muscular dystrophy? What kind?

They also may ask you questions about how your child plays, moves, and speaks, as well as how they act at home and at school.

The doctor may use different tests to check for conditions that can cause muscle weakness.

• Blood tests. They check for levels of certain enzymes that muscles release when they are damaged.
• Electromyography, or EMG. Your doctor will put small needles, called electrodes, on different parts of your child’s body and ask them to slowly flex and relax their muscles. The electrodes are attached with wires to a machine that measures electrical activity.
• Muscle biopsy. Using a needle, your doctor removes a small piece of your child’s muscle tissue. They’ll look at it under a microscope to see which proteins might be missing or damaged. This test can show the type of muscular dystrophy your child may have.
• Tests of muscle strength, reflexes, and coordination. These help doctors rule out other problems with their nervous system.
• Electrocardiogram or EKG . It measures electrical signals from the heart and tells how fast your child’s heart is beating and if it has a healthy rhythm.
• Imaging can show the quality and amount of muscle in your child’s body. They may get:
  • MRI, or magnetic resonance imaging. It uses powerful magnets and radio waves to make pictures of their organs.
  • Ultrasound, which uses sound waves to make pictures of the inside of the body.

Doctors can also test a sample of their blood to look for the genes that cause muscular dystrophy. Genetic tests can help diagnose the condition, but they’re also important for people with a family history of the disease who are planning to start a family. You can talk with your doctor or a genetics counselor to find out what the results of this test mean for you and your children.

Questions for Your Doctor

You’ll want to find out as much about your child’s condition as you can to learn how they can stay as healthy as possible. You may want to ask:

• What kind of muscular dystrophy do they have?
• Do they need any more tests?
• Do we need to see any other doctors?
• How will the disease affect their life?
• What kinds of treatments are available?
• How will they make them feel?
• What can I do to keep their muscles strong?
• Are there any clinical trials that would be good for them?
• Will my other children get muscular dystrophy?