Mesenchymal stem cells (MSCs) are considered to be an effective tool for treating chronic diseases due to their multi-lineage differentiation potential, immune regulatory capabilities, and ability to secrete anti-inflammatory factors. Increasingly, scientists are applying MSCs in clinical research for the treatment of chronic diseases such as neurodegenerative diseases, autoimmune diseases, and cardiovascular diseases and have achieved positive clinical outcomes.
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
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[2] Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases
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[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/
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https://pubmed.ncbi.nlm.nih.gov/24661633/
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