by admin | Jan 3, 2024 | ALS, Stem Cell Research, Stem Cell Therapy
Amyotrophic lateral sclerosis (ALS) is a rare, deadly progressive neurological disease that affects the upper and lower motor neurons. Characterized by weakening and gradual atrophy of the voluntary muscles, ALS gradually affects the ability to eat, speak, move, and eventually breathe.
With an estimated survival rate of 2 to 5 years from disease onset, 90% of ALS patients develop sporadic ALS and there is no known cure. Although the cause of ALS remains unknown, there is scientific evidence that both genetics and environment are key contributors. This evidence includes over 30 different gene mutations and a number of environmental factors (exposure to toxins, heavy metals, pesticides, smoking, and diet) have been found to be associated with neurological destruction and ALS development. Additionally, ALS has been found to be approximately 2 times more likely to occur in men than women.
In the search for a definitive cure for ALS, the use of mesenchymal stem cells (MSCs) for both treatment and management of the condition has been increasingly more common in preclinical and clinical studies.
In this review, Najafi et al. discuss multiple aspects of ALS and focus on MSCs’ role in disease management as demonstrated in clinical trials.
MSCs are multipotent cells with immunoregulatory, anti-inflammatory, and differentiation abilities that make them a strong candidate for use in therapeutic applications intending to expand the lifespan of ALS patients.
To date, preclinical research investigating the cause and potential treatment of ALS primarily relies on data gathered from rat and mouse models. As part of these models, researchers have discovered that the transplantation of MSCs through multiple routes (including intrathecal, intravenous, intramuscular, and intracerebral) can be a safe and effective way to delay the decline of motor function and promote neurogenesis.
These preclinical studies have also demonstrated that the administration of MSCs from specific tissues has shown significant advantages in delaying the degeneration of motor neurons, improving motor function, and extending lifespan.
Over 20 years of clinical research have found that direct injection of autologous expanded MSCs is safe and well tolerated and demonstrated a significant decrease in disease progression and increase in life expectancy in patients.
The authors conclude that ALS is a fatal neurodegenerative disease with no definitive cure. However, several preclinical and clinical studies have shown that MSC’s anti-inflammatory, immunoregulator, and differentiation properties, have demonstrated to be a good therapeutic approach for treating ALS.
Source: Najafi S, Najafi P, Kaffash Farkhad N, et al. Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives. Iran J Basic Med Sci. 2023;26(8):872-881. doi:10.22038/IJBMS.2023.66364.14572
by admin | Dec 28, 2023 | Diabetes, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
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
by admin | Dec 21, 2023 | Lupus, Exosomes, Extracellular Vesicles, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
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.
Source: “Immunomodulatory Effect of MSCs and MSCs-Derived Extracellular ….” 16 Sep. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481702/.
by admin | Dec 14, 2023 | Parkinson's Disease, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
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.
Source: “The potential use of mesenchymal stem cells and their exosomes in ….” 28 Jul. 2022, https://stemcellres.biomedcentral.com/articles/10.1186/s13287-022-03050-4.
by admin | Dec 7, 2023 | Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Stem cells respond to signals released by damaged or diseased tissue by differentiating in an effort to replace these cells.
As researchers continue to learn more about the various applications of stem cells as they relate to the body’s healing process, they’ve discovered two significant issues relating to the process of stem cell application. The first issue involves various methods that enable the stem cell transformation to targeted cells or successful engrafting. The authors of this review indicate that there are many proposed solutions to this issue, which are not covered as part of this review.
In this review, Maric et al. address the second known issue, analyzing cell homing. More specifically, understand how to direct the migration of most of the transferred cells to the desired location. Research has demonstrated that the greater the number of administered stem cells, the better the treatment outcomes. However, research has also indicated that there is a saturation plateau where no additional benefit has been achieved.
Previous studies have demonstrated positive results for non-invasive methods of stem cell transplant. However, it’s typical for stem cells to dissipate to other organs rather than to the brain, which are the targeted areas for a wide spectrum of neurodegenerative diseases.
Reviewing the existing research on stem cell homing, the authors draw a number of conclusions, including the location of the stem cell injection site impacts the homing results with better migration results when injections are closer to the targeted locations; preprocessing may increase homing efficiency; there are a number of potential methods that may improve the homing mechanisms; understanding the mechanism of neurodegenerative disease is essential to understanding the homing process and to predict the engraftment results; stem cells improve the plasticity of the brain; and that intrathecal application has many benefits, fewer adverse effects, and has been shown to be safe.
Additionally, Maric et al. raise issues that require further study, including evaluating the discrepancy between in vivo and in vitro results; paying more attention to the prospects of mathematical, physical, and computer models and simulations; investigation of real-time development and spatial information of the homing processes; and the need for a deeper understanding of homing mechanisms in homing mechanisms in intrathecal and other ways of administration.
The authors conclude that, in the case of neurodegenerative diseases, intrathecal application of stem cells via direct delivery to the cerebrospinal fluid has the advantage of no blood-brain barrier restriction, further study into the long-term study of what specifically slows the migration of injected cells is required.
Source: “Stem Cell Homing in Intrathecal Applications and Inspirations … – NCBI.” 13 Apr. 2022, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027729/.
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