Multiple sclerosis (MS) is a progressive autoimmune disease that affects the brain, spinal cord, and central nervous system (CNS). Affecting an estimated 3 million people worldwide, MS is typically characterized by an autoimmune response that results in inflammation, demyelination, and degeneration of axons.
Most patients who are diagnosed with MS demonstrate a disease progression characterized by periods of relapse and remission that can last for an extended duration.
There is no treatment that can yet address the various rates of MS progression. Additionally, current therapeutic approaches are designed to address the shortening of the duration of recovery following an attack, mitigating the progression of the disease, and attenuating the symptoms associated with MS.
Recently, mesenchymal stem cells (MSCs) have shown various ranges of effectiveness when used for treatment of autoimmune diseases in clinical trials. However, most of the trials utilizing MSCs for this purpose have been reported for a variety of reasons, including a low number of treated subjects, different doses used in the studies, the feasibility of autologous or allogeneic transplantation, and the unclear therapeutic window after the treatment effect.
Considering this, the purpose of Islam et al.’s systematic review and meta-analysis (SRMA) was to provide a comprehensive assessment of the effectiveness and safety of MSC therapy in individuals diagnosed with MS. To achieve this, the authors identified studies that reported on the efficacy and safety of MSC therapy in human patients with MS based on the changes in the Expanded Disability Status Scale (EDSS) score from baseline to follow-up period. This screening process resulted in a total of 30 studies being incorporated into the systematic review and 22 studies being included in the subsequent meta-analysis.
Islam et al. reported that, following MSC therapy, it was observed that 40.4% of the patients with MS experienced improvement; 32.8% of patients remained stable while 18.1% experienced a worsening of their condition. In terms of the safety of MSC therapy, the authors reported that while no major complications were observed, headaches (57.6%), fever (53.1%), urinary tract infections (23.9%), and respiratory tract infections (7.9%) were the most commonly reported adverse events.
While further research, the development of new technology, optimization of MSC doses, and larger clinical trials are needed to fully evaluate the use of MSC therapy in the treatment of MS, the authors conclude that the results of this SRMA indicate that MSC therapy seems to be an efficacious therapeutic strategy for treating patients with MS.
Source: Islam MA, Alam SS, Kundu S, Ahmed S, Sultana S, Patar A, Hossan T. Mesenchymal Stem Cell Therapy in Multiple Sclerosis: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2023; 12(19):6311. https://doi.org/10.3390/jcm12196311
Osteoarthritis (OA) is a chronic joint condition that causes pain and lack of mobility through the progressive degradation of joint cartilage. While there are several current pharmaceutical, physical therapy, and surgical treatments to address the symptoms of OA, researchers are interested in developing new therapeutic treatment approaches to address the relentless progression of the condition.
Considering their documented biocompatibility, immunomodulatory properties, and ability to precisely target specific cells and tissues, exosomes have recently emerged as a promising therapeutic option as a drug delivery system (DDS) for the treatment of OA. Specifically, these exosome-based strategies have demonstrated a safe and effective way to enhance cartilage repair, mitigate inflammation, and alleviate the persistent pain associated with OA.
While the benefits of exosome-based DDSs have been demonstrated in numerous studies, according to the author of this review, the specific application of this option for the purpose of treating OA has not been sufficiently explored.
In this review, Lu et al. summarize the emerging developments surrounding exosome-based DDSs of OA and highlight the present challenges associated with this evolving therapeutic option.
Recent studies have demonstrated the benefit of using exosomes for the delivery of drugs designed to treat OA. Specifically, researchers have found that exosomes derived from mesenchymal stem cells (MSCs) are able to be effective carriers for the delivery of specific molecules that lead to the promotion of chondrogenesis and improvement in cartilage regeneration. These same exosomes have also demonstrated themselves to be effective carriers for the localized delivery of anti-inflammatory drugs known for their potent anti-inflammatory and immunosuppressive effects.
Other studies show the potential of exosomes as an effective way to deliver growth factors to the affected joint in a targeted and sustained manner. The same exosomes have also demonstrated promise as a platform for gene delivery to areas affected by OA; a few of the notable advantages include the ability to safeguard genetic material from degradation and enable targeted delivery to specific cells and tissues.
While there is seemingly unlimited potential for using exosomes as DDSs in OA treatment, Lu et al. also call attention to several technical challenges and limitations that need to be addressed in order to fully maximize their potential and to ensure their safe application. These challenges and limitations include figuring out how to obtain a consistent supply of high-quality exosomes, developing effective methods that allows for efficient loading and controlled release of therapeutic molecules within exosomes, and a current lack of comprehensive long-term data regarding the safety and biocompatibility of exosome-based therapies.
Despite these challenges and limitations, the authors conclude that exosomes have emerged as highly promising candidates for drug delivery in OA therapy and offer numerous advantages over conventional delivery systems.
Source: Jun Lu, Yan Zhang, Xinquan Yang, Hongmou Zhao, Harnessing exosomes as cutting-edge drug delivery systems for revolutionary osteoarthritis therapy, Biomedicine & Pharmacotherapy, Volume 165,2023,115135, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2023.115135.
Type 2 diabetes mellitus (T2DM) is a serious health condition characterized by progressive deterioration in glycemic control resulting from decreased insulin sensitivity and diminished insulin secretion. Currently, it is estimated that over 462 million people worldwide are affected by T2DM.
While diet, physical exercise, and glucose-lowering medications have been shown to improve hyperglycemia, the results have been temporary and have not been able to inhibit the pathogenesis or reduce the morbidity associated with this condition.
With the need for more effective approaches for the treatment of T2DM to be developed, Zang et al. conducted this single-center, randomized, double-blinded, placebo-controlled phase II trial study to explore the efficacy and safety of intravenous infusion of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in Chinese patients with T2DM.
MSCs are a type of adult stem cell that exhibits profound anti-inflammatory and immunomodulator capacities. Considering the successful application of MSCs in a number of autoimmune diseases, including stroke, myocardial infarction, rheumatoid arthritis, and systemic lupus erythematosus, the authors hypothesized that MSC transplantation might also be a therapeutic option for the treatment of T2DM.
Specifically for this study, the authors randomly assigned 91 patients to receive intravenous infusion of UC-MSCs or placebo three times at 4-week intervals and followed up for 48 weeks over a period of three years.
The primary endpoint established for this study was the percentage of patients with glycated hemoglobin (HbA1c) levels of < 7.0% and daily insulin reduction of > 50% at 48 weeks; additional established endpoints included changes of metabolic control, insulin resistance, and safety.
At the end of the 48-week follow-up period, Zang et al. report that 20% of patients in the US-MSCs group and 4.55% reached the primary endpoint with the percentage of insulin reduction of the UC-MSCs group being significantly higher than that of the placebo group. The authors also reported that the glucose infusion rate (GIR) increased significantly in the UC-MSCs group while there was no significant observed change in the placebo group. There were also no major UC-MSC transplantation-related adverse events reported during this study.
While these results are promising, the authors point out that since the age, course of T2DM, condition of the islet β-cell function, and insulin resistance of the enrolled subjects were highly heterogeneous, the results of this study could not be extended to all patients with T2DM. The authors also call for additional long-term follow-up to validate their initial, short-term findings as well as for future well-controlled studies with an increased number of cases to better clarify the efficacy and safety of intravenous infusion of UC-MSCs for the treatment of T2DM.
The authors conclude this study by suggesting intravenous infusion of UC-MSCs administration is a safe and effective approach that could reduce exogenous insulin requirements alleviate insulin resistance and be a potential therapeutic option for patients with T2DM.
Source: Zang, L., Li, Y., Hao, H. 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 13, 180 (2022). https://doi.org/10.1186/s13287-022-02848-6
According to the Centers for Disease Control and Prevention, more than 795,000 people have strokes every year in the United States, and about 610,000 of these are first or new strokes. Recovering from a stroke can be a complex process that involves many types of therapies, and one option that shows promise is stem cell therapy.
Stem cell therapy promotes growth factors and offers relief from inflammation, providing the possibility of healing the damage the stroke caused. Learn more about stem cell therapy when used for the recovery period after a stroke.
How Strokes Affect the Brain
A stroke is like a heart attack, except it takes place in your brain. It occurs when something blocks the blood supply to the brain, not allowing the organ to get the oxygen and nutrients it needs. If your brain doesn’t receive blood, its cells begin to die off or suffer damage, making it impossible for the organ to do its job.
Your brain controls everything your body does, including how you move and how you think, feel, and communicate. The results of a stroke are immediate.
The two main types of strokes are ischemic strokes and hemorrhagic strokes. Ischemic strokes are the most common type and are caused by blockages. They can occur when:
A blood clot forms in the main brain artery.
A blockage forms in the small blood vessels deep within the brain.
A blood clot from the heart or another type of blockage travels via the bloodstream to an artery supplying the brain.
Hemorrhagic strokes occur when there’s bleeding in or around the brain. They can be the result of a blood vessel bursting in the brain, or a blood vessel on the surface of the brain may burst and leak blood in the area between the skull and the brain.
When you have a stroke, the areas of the brain it affects determine the kind of issues you can struggle with.
Some people experience weakness and paralysis in certain parts of their body, while others struggle with language and the processes of speaking or understanding what other people say. A stroke can even affect what your voice sounds like.
Other issues you may experience include:
Balance problems
Incontinence
Trouble swallowing
Visual problems
Extreme fatigue
Feeling pain
You may also struggle with mental processes like memory, concentration, understanding, and perception. Strokes can even affect your emotions.
Understanding Stem Cell Therapy: What Are Stem Cells?
Stem cells are the body’s building blocks. They are responsible for creating organs, tissues, and even your immune system. They are undifferentiated cells that can become and create specialized cell types. In other words, they can become any cell within the body, depending on where they’re placed.
Stem cells can also divide indefinitely, either creating other stem cells or specialized cells. When used to help the recovery period after a stroke, stem cells can differentiate into brain cells.
When they’re used in the brain, they don’t integrate and become neurons that reconstruct circuits. They instead start pumping out growth factors that enhance the recovery process, allowing new blood vessels and neurons to form. All of this helps make the brain more flexible, giving it a chance to recover after a stroke.
Neuroplasticity is what’s necessary for people who’ve suffered a stroke. It is the ability of the brain to rearrange its circuits, basing the organization on your behaviors.
Benefits of Stem Cell Therapy After a Stroke
Stem cell therapy is minimally invasive. You don’t have to worry about procedures that require long recovery processes or force you to spend time in the hospital. When you get stem cell therapy, the process is fast and can be done as an outpatient treatment.
Stem cells don’t just mask the symptoms of the damage the stroke caused. Experiencing pain after a stroke many times means turning to pain medications, which temporarily give you relief but also have unpleasant side effects. When you turn to stem cell therapy, your brain gets what it needs to start healing.
One of the most important things that stem cell therapy offers is the chance to relieve inflammation. When you suffer an injury of any kind, including a stroke, your body’s natural healing process causes inflammation.
This type of swelling, however, doesn’t allow a regular flow of blood to the injured area. Without the right degree of circulation, the damaged area doesn’t receive nutrients or oxygen, which makes healing more difficult. Stem cells help reduce inflammation, making the process of healing easier.
How the Stem Cell Therapy Process Works
Mesenchymal stem cells (MSCs) have been studied for their potential therapeutic applications in various medical conditions, including stroke. MSCs have several properties that make them attractive candidates for stroke therapy:
MSCs possess anti-inflammatory properties that can help modulate the immune response and reduce inflammation in the brain following a stroke. Excessive inflammation is a key contributor to secondary damage after a stroke.
MSCs can modulate the immune system, potentially suppressing harmful immune responses while promoting tissue repair and regeneration.
MSCs secrete various growth factors and neurotrophic factors that support neuronal survival, growth, and differentiation. These factors can contribute to the repair and regeneration of damaged neural tissue.
MSCs can stimulate the formation of new blood vessels (angiogenesis), which is crucial for supplying oxygen and nutrients to the damaged brain tissue.
While the ability of MSCs to differentiate into neurons is limited, they may contribute to neural repair indirectly by interacting with the local environment and supporting the survival of existing neurons.
Is Regenerative Medicine Right for You?
Suffering a stroke can be devastating, leaving you with lasting damage and impacting your quality of life. Along with physical therapy and other treatments your doctor recommends, patients are exploring their options with stem cell therapy. Stem cell therapy and other regenerative medicine options offer the opportunity to give your brain the tools it needs to start healing. By helping reduce inflammation and bringing growth factors to the treatment area, stem cell therapy provides the chance to promote neuroplasticity and start healing.
Systemic lupus erythematosus (SLE) is a common multisystemic autoimmune disease that often results in multi-organ damage when left untreated. Currently affecting over 1.5 million Americans, the etiology and pathogenesis of SLE continue to remain unclear.
At present, glucocorticoids and immunosuppressants are the most prescribed course of therapeutic treatment and mostly as a way to manage and treat symptoms of SLE, not the cause itself.
Considering that the etiology and pathogenesis of SLE are accompanied by immune disorders including abnormal proliferation, differentiation, and activation and dysfunction of T cells, and that mesenchymal stem cells (MSC) and MSC-derived extracellular vesicles (EVs) play important roles in the immunity process, researchers are increasingly turning their attention to MSCs and EVs as potential therapeutic treatment options for SLE.
In this review, Yang et al. examine the immunomodulatory effects and related mechanisms of MSCs and EVs in SLE with hopes of better understanding SLE pathogenesis and guiding biological therapy.
Examining the potential use of MSC and MSC-EVs in SLE treatment the authors found some studies have established that MSCs reduce adverse effects of immunosuppressive drugs and when combined have demonstrated distinct effects on T cell activation and bias.
Additionally, Yang et al. report that MSCs are able to participate in the immune response in two distinct ways: paracrine effect and directly through cell-to-cell interaction. Since reconstruction of immune tolerance and tissue regeneration and repair are required parts of SLE treatment and since MSCs possess high self-renewal ability, rapid expansion in vitro and in vitro, and low immunogenicity, allogeneic MSC transplantation has demonstrated strong evidence for the therapeutic potential of MSC in SLE.
Besides the ability to repair and regenerate tissue, MSCs, and MSC-EVs have strong anti-inflammatory and immunomodulatory effects, making them a potentially ideal treatment option as part of a therapeutic strategy for SLE. Considering that MSC-EVs have similar biological functions with MSCs, but are also considered cell-free, the authors point out that MSC-EVs could be the better choice for SLE treatment in the future.
Despite the potential of MSC and MSC-EVs, Yang et al. point out that genetic modification, metabolic recombination, and other priming of MSCs in vitro should be considered before MSC/MSC-EVs application for SLE treatment. The authors also recommend further clinical evaluation of the time of infusion, appropriate dosage, interval of treatment, and long-term safety of MSC/MSC-EVs in the treatment of SLE before any form of the combination is used as a treatment option.
Parkinson’s disease (PD) is the second most predominant neurodegenerative disorder worldwide, affecting over 10 million people. Characterized by a slow and progressive loss of control of the neurological system as a result of dopamine depletion, symptoms of PD often include tremors, slowed movement, impaired posture and balance, and gradual loss of automatic movements.
While PD cannot be cured, current treatment is focused on alleviating symptoms and slowing the progression of the disease. Specifically, deep brain stimulation or therapies to increase DA levels by administering a DA precursor are the available therapy options for PD.
However, research has found that DA precursor therapy has little effect on the progression of PD and its efficacy decreases as the disease progresses.
Recent progress in the clinical understanding of regenerative medicine and its properties associated with stem cell therapy has provided the opportunity to evaluate new and potentially effective methods for treating a wide range of neurodegenerative illnesses, including PD. Specifically, mesenchymal stem cells (MSCs) have been found to be the most promising form of stem cell and have demonstrated the ability to differentiate into dopaminergic neurons and produce neurotrophic substances.
In this review, Heris et al. discuss the application of MSCs and MSC-derived exosomes in PD treatment.
Research has identified dysregulation of the autophagy system in the brains of PD patients, suggesting a potential role for autophagy in PD. In PD models, MSCs may activate autophagy signals and exhibit immunomodulatory effects that alleviate inflammation and improve tissue healing; this type of treatment had previously been used in treating various forms of neuroinflammatory and neurodegenerative illnesses.
The authors indicate that MSCs can be administered either systemically or locally. While systemic transplantation allows MSC-based treatment of pathologies affecting the entire body, local transplantation aims to alleviate symptoms associated with illnesses that originate from certain organs and is performed through intramuscular or direct tissue injection.
Research has also demonstrated that stem cell-derived dopaminergic transplants could be a suitable method for the long-term survival and function of transplants; in the case of MSC therapy, the average dose in animal models is usually 50 million cells for each kg of weight.
MSC-derived exosomes demonstrate therapeutic characteristics similar to their parents, have the ability to avoid whole-cell post-transplant adverse events, have a high safety profile, cannot turn into pre-malignant cells, and no cases of immune response and rejection have been reported.
While the use of MSCs in the treatment of PD continues to show potential, Heris et al. point out that many of the clinical trials have had few participants and can be costly. Considering these limiting factors, the results from these studies are not able to be generalized to everyday medical care without further clinical studies to address these concerns.
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