Muscular Dystrophy progressively weakens muscles due to genetic mutation present in muscle cells. The gradual deterioration impairs motor functions and subsequent limb movements. Although it can manifest at any age, it is detectable during childhood. It is also associated with visual disturbances, gastrointestinal disorders, and cognitive dysfunction. The muscular degeneration eventually spreads to key organs such as the heart and lungs. It leads to chronic medical illnesses and a short survival period. The involvement of processes such as inflammation and fibrosis adds to the complexity of the disorder.
The therapeutic interventions using a combination of medications and rehabilitative therapies prolong muscle movement and slow the disease progression. A search for an alternative therapy has led to Stem Cell Treatment for Muscular Dystrophy. It has been beneficial in treating several disorders by employing a regenerative approach. With the ability to improve muscle function, stem cell therapy can be an effective solution for muscular dystrophy.
Stem Cell Treatment for Muscular Dystrophy
Muscle injury usually triggers a repair pathway. However, muscular dystrophy patients lack this process due to the mutation that forms dysfunctional proteins. Stem cells can transform or differentiate into diverse cell types, including muscle cells or fibers. They do not carry the mutation present in the muscle fibers of patients. Therefore, stem cells can form healthy muscle fibers that lack the mutation and thus facilitate the healing and regeneration of muscles. It also addresses the multiple genetic mutations of the disorder, eliminating the need for individual therapy for every mutation. Mesenchymal stem cells (MSCs) are popular in the field of regenerative medicine. They act in the following manner to treat muscular dystrophy:
- Drive muscle regeneration by secreting growth factors like osteopontin and CXCL12.
- Transform into muscle fibers and restore the expression of protein absent in the disorder like dystrophin.
- Boost blood vessel quantity by releasing VEGF.
- Regulate the immune system by transforming M1 macrophages into repair-inducing M2 macrophages.
- Alleviate inflammation by reducing the levels of TGFβ1, IL6, and TNFα while increasing IL4 and IL10.
- Support the maintenance of muscle stem cells.
- Increase muscle fiber size and decrease fibrosis.
Together, these pathways create a supportive environment for muscle repair and regeneration. In animal studies, MSC treatment has shown extended survival.
Can Stem Cells Cure Muscular Dystrophy?
In 2021, a team of scientists in Poland conducted a clinical study on 22 patients belonging to different genders and age groups. It also encompassed different types of muscular dystrophy. These patients were administered umbilical cord MSCs (UC-MSCs). After treatment, the patients showed significant improvements in limb movement, hip straightening, and elbow straightening. Many patients showed improvement in gait. One patient even gained movement, no longer needing crutches. The therapy was well-tolerated, with one patient experiencing a temporary headache and lower back pain.
Li et al. evaluated the treatment with UC-MSCs in Becker Muscular Dystrophy and reported an increase in muscle strength and size along with diminished levels of creatinine kinase and lactate dehydrogenase biomarkers. Karaoz et al. demonstrated that infusion of UC-MSCs increased dystrophin-producing cells and improved lung function in Duchenne muscular dystrophy. These studies also reported that the treatment had no adverse effects.
Advances in Stem Cell Therapy
Besides stem cell therapy, many scientific advancements continue to develop a suitable treatment for muscular dystrophy.
Gene Therapies
Gene therapy entails the introduction of a functional copy of a gene in cells carrying the mutated or dysfunctional gene. It can restore the expression of a protein deficient in patients’ cells and improve muscle function. Gene therapy in animal models increased the expression of dystrophin protein and muscle strength. However, they used viral-based gene delivery methods that induce an immune response. Therefore, non-viral delivery of genes is under investigation. Another approach to gene therapy is to extract a patient’s cells and correct the genetic mutation in them using viral-based gene therapy. The reinfusion of these cells in the patient offers increased dystrophin expression and improved muscle function without eliciting an immune response.
Exosomes
It has come to light that MSCs exert their influence by releasing exosomes- tiny vesicles containing a plethora of biomolecules. The mRNAs present in these exosomes promote muscle regeneration and reduce fibrosis. Research by Bier et al. demonstrated that miR-29c alleviated fibrosis in the lungs and heart muscles. It also suppressed inflammation and resulted in a decrease in serum creatinine kinase levels. Due to their cell-free alternative, exosomes might have more potential in the treatment.
Stem Cell-Derived Muscle Cells
Scientists have been trying different approaches to maximize the potential of stem cell therapy for the disorder. Therefore, instead of injecting MSCs, they have differentiated MSCs into muscle stem cells or progenitors. After transplantation, stem cell-derived muscle stem cells differentiate into muscle fibers and drive regeneration according to studies on mice and rats. Based on this concept, two products have emerged- MyoPAXon and GIVI-MPC. Both constitute stem cell-derived muscle progenitors for treating Duchenne and Becker muscular dystrophy. They have received approval from the US FDA to conduct clinical trials.
Chimeric Cells
In a novel cell therapy approach, Dr. Siemionow developed chimeric cells by fusing a patient’s muscle stem cells with MSCs from a healthy donor. Since the cells contain the patients’ cellular part, they would not cause an immune response, a potential risk in other cell-based therapies. In the initial phase, studies on animals showed significant functional improvements in skeletal muscles, heart muscle, and lung muscles. Reduction in fibrosis and inflammation was also evident. In a clinical trial, the transplantation of these chimeric cells demonstrated similar results. The improvements were sustained at 12-month follow-up, indicating halting of the disorder progression. The study reported that no adverse events occurred due to the treatment. This therapy combines the advantages of stem cells and gene therapy while eliminating their individual risks.
Muscular Dystrophy Treatment Success Stories
Concluding Remarks
Muscular dystrophy occurs due to genetic mutations. The treatment modalities have limited impact on improving muscle function and can only slow the disease progression. It requires the regenerative approach of stem cell therapy. They can develop healthy muscle cells that do not carry the mutation. Since MSCs are easy to harvest and expand in the laboratory without any ethical considerations, they can serve as remarkable therapeutic agents. The research on animals has shown that the anti-inflammatory and anti-fibrotic properties of MSCs can create a supportive environment in the tissue. It has led to clinical trials of MSCs treatment in patients. The trials demonstrated improvements in muscle strength along with increased limb movements in many patients. The treatment didn’t cause any adverse effects. Stem cells are creating a paradigm shift in the treatment of muscular dystrophy. Advancells is supporting this transition by delivering premium-quality stem cells in India.
FAQ’s
Q- What causes muscular dystrophy?
It occurs due to a genetic mutation that results in the formation of dysfunctional proteins or leads to a deficiency of a protein essential to muscle cell structure and function.
Q- How do stem cells treat muscular dystrophy?
Stem cells transform into healthy muscle cells that lack the genetic mutation. These cells can thus restore muscle strength and functions.
Q- Is stem cell therapy effective?
The clinical trials on stem cell treatment for muscular dystrophy have shown positive results such as improvements in limb movements, hip straightening, and lung functions. The therapy did not result in any complications, thus deeming it safe for use.
Q- How many sessions of stem cell therapy are required?
While many studies have used a single infusion, some studies have generated favorable outcomes with four sessions. The final number of sessions, however, depends on disease severity and individual factors.
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