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/.
by admin | Nov 23, 2023 | Autoimmune, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Recent estimates indicate that one in every 10 people is affected by an autoimmune disease.
Autoimmune diseases occur when the normal function of the immune system mistakenly attacks normal and healthy cells within the body; examples of autoimmune diseases include rheumatoid arthritis, type 1 diabetes, and lupus. Currently, there are over 80 known types of autoimmune disease.
Because of their proliferation and differentiation ability, mesenchymal stem cells (MSCs) have increasingly drawn interest from the research community as a potential option for the treatment of autoimmune diseases.
In this study, Zeng et al. evaluate the efficacy and safety of MSC transplantation in the treatment of autoimmune diseases. Specifically, this review included a total of 18 RCTs involving rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBS), ankylosing spondylitis (AS), and multiple sclerosis (MS).
Reviewing the therapeutic effects of MSCs on each of the diseases, the authors found that with the exception of MS, transplantation of MSCs may improve clinical symptoms and clinical efficacy of these autoimmune diseases. However, the authors also point out that MSCs appear to produce certain specific effects on different autoimmune diseases.
Although no obvious adverse events resulting from MSC transplantation were reported or observed during these studies, and while MSCs appear to have certain effects on different autoimmune diseases, the authors conclude that this review provides relevant evidence for the design of future clinical trials specifically assessing MSC cell source, dosage, route of drug administration, and intervention in the most ideal disease state when treating this group of diseases.
Source: “Efficacy and Safety of Mesenchymal Stem Cell Transplantation in ….” https://www.hindawi.com/journals/sci/2022/9463314/.
by admin | Nov 16, 2023 | Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Ankylosing spondylitis (AS) is a progressive, inflammatory rheumatoid disease that, over time, can result in chronic spinal arthritis and can cause the vertebrae to fuse together. Affecting an estimated 300,000 people in the U.S., AS causes the spine to become less flexible and can result in a hunched posture.
There is no current treatment for AS and current drug therapy options are focused on reducing inflammation, stiffness, and back pain. While current treatments assist in reducing inflammation, many patients with AS continue to experience unresponsive or painful side effects from these drugs.
In the search for a cure for AS, stem cells – and specifically, mesenchymal stem cells (MSCs) have emerged as a potentially promising treatment option. Specifically, researchers believe the immunomodulatory and regenerative properties demonstrated by MSCs could reduce inflammatory responses and help tissue repair through cell-to-cell contact and secretion of soluble factors.
In this review, Abdolmohammadi et al. describe immunopathogenesis and current treatment restrictions of AS and discuss the recent findings of clinical trials involving MSC therapy in AS.
The safety and therapeutic potency of MSC therapy have been shown in many types of research. While there are currently a number of in-process clinical trials exploring MSC transplantation in related disorders, the transplantation of MSCs is a therapeutic option for AS patients who cannot tolerate the anti-inflammatory drugs.
Previous studies have demonstrated MSC infusion in AS patients to be a safe and beneficial choice with no severe side effects and is effective in decreasing related clinical symptoms and severity of the disease. There are also a number of clinical trials for curing AS patients currently in progress. These trials include phase 1 exploring the application of human umbilical cord-derived MSCs (hUC-MSCs) and IV infusion of MSCs plus NSAIDs in AS patients, phase 2 of a clinical trial evaluating human bone marrow-derived MSCs application in AS patients, and clinical trial phase I/II for the safety of MSC transplantation in patients with AS.
Although there have been notable achievements in the treatment of AS using NSAIDs, glucocorticoids, and other drugs, a therapeutic option without side effects has yet to be discovered. MSCs offer a favorable treatment option for the treatment of immune-mediated disorders, including AS.
While findings of previous studies demonstrate that MSC injection might be beneficial in alleviating AS signs and symptoms, the authors point out that further study is required to determine several important features of MSC therapy, including cell origin, dosage, administration route, and the most ideal stage of disease for intervention, before it can be accepted as a clinical option for treating AS.
Source: “Ankylosing spondylitis and mesenchymal stromal/stem cell therapy.” https://www.sciencedirect.com/science/article/pii/S0753332218356762.
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