by admin | Nov 29, 2024 | Mesenchymal Stem Cells, Multiple Sclerosis, Neural Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that can take different forms: relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive (PPMS). In RRMS, symptoms flare up and then ease, largely due to inflammation, and there are many therapies to manage these relapses. In SPMS and PPMS, the disease gradually progresses without relapses, leading to accumulating disability. Treatments for these progressive forms are limited, and the therapies available are generally less effective than for RRMS.
In this study, Harris et al. explores the use of stem cell-based treatment, specifically mesenchymal stem cell-derived neural progenitors (MSC-NPs), for people with progressive MS.
MSC-NPs are cells derived from a patient’s own bone marrow and have potential regenerative and immune-modulating effects. Early research suggests that MSC-NPs can provide beneficial effects in animal models of MS.
This clinical trial was initiated to test the safety and early efficacy of MSC-NPs when injected directly into the spinal fluid of patients with progressive MS. Specifically, Harris et al. wanted to see if these patients would experience fewer or slower disease-related declines after receiving repeated injections of MSC-NPs.
Evaluating Safety and Early Efficacy Trends
According to the authors, this study found that repeated injections of MSC-NPs were generally safe. Over the two-year follow-up period, no serious side effects were reported by any of the patients. A minor headache was reported by one patient, which did not require treatment, and some other minor issues were reported but were deemed unrelated to the study treatment.
This confirms the long-term safety of MSC-NPs, which is critical as cell therapies become more widely tested for neurological diseases like MS.
While Harris et al.’s study was not designed to determine whether MSC-NPs were definitively effective, some additional trends were observed:
- Patients with lower levels of disability at the start of the study tended to show more improvement in their mobility and overall functioning than those with higher disability scores.
- Most patients who benefited were those who could still walk when they started the trial, suggesting MSC-NP therapy might be more effective in people with less advanced disability.
- Of the three patients with primary progressive MS, two showed stable disability scores over the two years following treatment. However, the sample size was too small to draw firm conclusions on its effects in PPMS compared to SPMS.
While these findings are promising, the study has significant limitations. With only 20 patients, the study was too small to determine definitive efficacy, so a larger, placebo-controlled trial is necessary to confirm any potential benefits of MSC-NPs.
Additionally, the open-label design, where both patients and researchers knew who was receiving the treatment, could mean that some effects may have resulted from a placebo response rather than the treatment itself. Furthermore, the therapy may be more effective for patients with lower disability scores, but more research is required to identify which patients are the most suitable candidates for MSC-NP treatment.
Future Directions for MSC-NP Therapy in Progressive MS
Harris et al.’s study has laid the groundwork for further research by establishing MSC-NPs as a safe treatment option over a two-year period. Based on these findings, a larger Phase II trial is underway, involving 50 patients who will receive MSC-NP injections or a placebo over an extended period. This trial will be double-blinded (neither patients nor researchers will know who is receiving the treatment) to give more definitive answers about MSC-NP’s effects on progressive MS.
In summary, MSC-NPs appear to be a safe treatment option for people with progressive MS, with some early evidence suggesting potential benefits in reducing disability for those with less advanced disease. These findings contribute to the understanding of cell-based therapies in MS and support further exploration of MSC-NPs in larger, controlled studies. While MSC-NPs offer hope for future therapies, the authors call for more rigorous research to clarify their impact on long-term disease progression and patient quality of life.
Source: Harris VK, Stark JW, Yang S, Zanker S, Tuddenham J, Sadiq SA. Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year follow-up of a phase I study. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 4;8(1):e928. doi: 10.1212/NXI.0000000000000928. PMID: 33277427; PMCID: PMC7738177.
by admin | Nov 22, 2024 | Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Since their discovery in 1960, mesenchymal stem cells (MSCs) have been extensively studied for their potential to treat a wide range of diseases, including autoimmune diseases, bone/cartilage repairs, diabetes, cardiovascular diseases, and neurological and immune-related disorders.
MSCs have demonstrated the ability to improve these conditions through their ability to repair injured or affected tissue by migrating to the injured site, engrafting, and differentiating to end-stage functional cells. Additionally, MSCs have shown the ability to modulate immune cell types, promote neovascularization, increase angiogenesis, enhance cell viability, and inhibit cell death.
While the results of several animal studies exploring the therapeutic benefits of MSCs have been promising, the lack of therapeutic results demonstrated from some clinical trials has created the need to further explore and understand the specific role of MSCs as a viable treatment option.
In this review, Fan et al. summarize the mechanisms underlying the protective effects of MSCs and provide an overview of recent developments in MSC-based therapy.
The authors attribute the therapeutic potential of MSCs to two primary aspects, replacement of the damaged tissue through differentiation and regulation of immune responses by immunomodulatory function. These aspects are specifically attributed to the paracrine function, which secretes a variety of factors to exert immunomodulatory, angiogenic, antiapoptotic, and antioxidative effects.
Fan et al. point out that although MS-based therapies have made significant progress, clinical trials and publications demonstrating mixed and contradictory results have prevented the advancement of MSCs into daily clinical application. The authors conclude that these disparities are most likely due to the large variability in key factors such as cell source, dosage, administration route, and administration timing.
Considering these disparities, Fan et al. call for the standardization of procedures of MSC isolation and expansion as crucial to improving the safety, efficacy, and outcomes of future clinical investigations of MSC-based therapies.
Source: Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci. 2020;77(14):2771-2794. doi:10.1007/s00018-020-03454-6
by admin | Nov 15, 2024 | Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy, Uncategorized
Mesenchymal stem cell (MSC) therapy has gained attention as a potential treatment for decompensated liver cirrhosis (DLC), a severe form of liver disease that occurs when the liver can no longer function properly. Liver cirrhosis, especially when caused by chronic hepatitis B (HBV), leads to a significant decline in health, and current treatments do not always yield long-term benefits.
MSCs, particularly those derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC), have shown promise in improving liver function in both animal and human studies. However, the long-term safety and efficacy of MSC therapy, especially in human patients with liver diseases like DLC, remain uncertain. Shi et al.’s study sought to address this gap by observing the effects of UC-MSC therapy in patients with decompensated liver cirrhosis over a follow-up period of 75 months.
Introduction
In recent years, MSC therapy has emerged as a novel approach for treating liver disease, particularly cirrhosis. Research on animal models has demonstrated that bone marrow-derived MSCs (BM-MSCs) can reduce liver fibrosis and even reverse acute liver failure. These findings have also extended to clinical settings where BM-MSC infusions have significantly improved liver function in patients with cirrhosis. Additionally, UC-MSC therapies have been explored, with early studies demonstrating their potential to safely and effectively treat autoimmune-related cirrhosis and improve outcomes in patients with chronic liver failure.
While early studies show promising short-term benefits, there is still limited knowledge about the long-term safety and efficacy of MSC treatments for liver disease. Most studies have only followed patients for up to 12 months. This study aimed to explore the long-term impact of UC-MSC therapy on patients with HBV-related decompensated liver cirrhosis over a period of 75 months, the longest follow-up recorded to date.
Effects of UC-MSC on Long-Term Survival
The primary goal of Shi et al.’s study was to evaluate the long-term survival rates of patients in both groups. Initially, there was no significant difference in survival rates between the UC-MSC group and the control group. However, by using a landmark analysis, the researchers discovered that patients in the UC-MSC group had a significantly higher survival rate during the 13 to 75-month follow-up period, although no notable difference was observed during the first 13 months.
These findings suggest that UC-MSC treatment may take some time to show its full benefits. After the initial 13 months, patients who received UC-MSC therapy experienced improved survival rates compared to those who received only conventional treatment.
Impact of UC-MSC Infusion on Liver Function
To assess the effect of UC-MSC therapy on liver function, the researchers monitored key markers such as albumin (ALB), prothrombin activity (PTA), cholinesterase (CHE), and total bilirubin (TBIL) levels. Results showed that patients in the UC-MSC group experienced significant improvements in ALB and PTA levels compared to the control group during the 48-week follow-up. Additionally, although CHE levels were initially lower and TBIL levels were higher in the UC-MSC group at baseline, these markers improved following the UC-MSC infusions.
The results suggest that UC-MSC therapy helps reduce liver inflammation and enhances liver function over time, improving the liver’s ability to produce essential proteins and process waste products.
Safety and Adverse Effects of UC-MSC Infusion
One of the key concerns in MSC therapy is its long-term safety, particularly the risk of developing hepatocellular carcinoma (HCC) or other complications. In this study, seven patients in the UC-MSC group experienced mild, self-limiting fevers after their infusions, but no other significant short-term side effects were reported.
Over the long term, both groups had similar rates of HCC development, indicating that UC-MSC therapy does not increase the risk of liver cancer compared to standard treatment. Importantly, no other major adverse effects were observed during the 75-month follow-up, suggesting that UC-MSC therapy is a safe option for patients with decompensated liver cirrhosis.
Challenges and Next Steps in UC-MSC Therapy for Liver Cirrhosis”
Despite the positive findings, this study had some limitations. For instance, liver biopsies were not performed due to the high risk for patients with decompensated liver cirrhosis, meaning that histological changes in the liver could not be directly observed. Additionally, the infused UC-MSCs were not tracked within the patients’ bodies due to technical and ethical concerns, leaving some questions about the specific mechanisms of their effect on liver function.
Future research should involve multi-center clinical trials to further explore the use of UC-MSC therapy and confirm the findings of this study. Understanding the precise mechanisms through which UC-MSCs improve survival rates and liver function would also be valuable in optimizing this treatment for liver cirrhosis.
The authors of this study conclude that UC-MSC therapy appears to be a safe and effective treatment option for patients with HBV-related decompensated liver cirrhosis. With improvements in liver function and survival rates becoming evident after 13 months, this treatment holds promise as a novel therapeutic strategy for managing end-stage liver disease.
Source: Shi, M., Li, YY., Xu, RN. et al. Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial. Hepatol Int 15, 1431–1441 (2021). https://doi.org/10.1007/s12072-021-10199-2
by admin | Nov 1, 2024 | Autoimmune, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
The purpose of Zeng et al.’s review and meta-analysis was to evaluate the efficacy and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune diseases.
MSCs have been found to have powerful immune regulation functions, multi differentiation potential, and the ability to promote hematopoiesis and tissue repair. These stem cells have also been used in the treatment of refractory and severe autoimmune diseases, providing patients with several safe and effective new treatment options.
In order to evaluate the efficacy and safety of MSCs in this capacity, Zeng et al. evaluated 18 randomized controlled trials (RCTs) that involved the following autoimmune diseases: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease, ankylosing spondylitis, and multiple sclerosis (MS).
Animal model RCTs evaluating MSC transplantation in the treatment of RA have shown that disease activity was weakened, and clinical symptoms were improved after receiving mesenchymal stem cell transplantation (MSCT).
Treating SLE with MSCs has demonstrated the ability to control disease progression, improve immune system damage, and relieve the condition of lupus in mice models. Other clinical trials demonstrated that MSCs, when transplanted, have been found to be safe while also providing significant clinical therapeutic effects.
In terms of IBS, the authors report that immune dysfunction is believed to play a key role in the occurrence and development of ulcerative colitis. Recent studies also suggest that MSCs might help tissue regeneration by suppressing inappropriate immune responses and providing various cytokines.
Additional research also demonstrated that MSC treatment for 6 months may increase the total effective rate and improve pain and activity associated with ankylosing spondylitis, while more RCTs are needed before a conclusion can be made for the effectiveness of this therapy for MS.
Considering the information obtained as part of this study, Zeng et al. concluded that there were no adverse events associated with MSC transplantation observed in the RCTs that were analyzed. The authors also concluded that MSCs have a certain effect on different autoimmune diseases, but additional RCTs are required to further modify or confirm these findings.
Source: Zeng L, Yu G, Yang K, Xiang W, Li J, Chen H. Efficacy and Safety of Mesenchymal Stem Cell Transplantation in the Treatment of Autoimmune Diseases (Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis, and Ankylosing Spondylitis): A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Stem Cells Int. 2022;2022:9463314. Published 2022 Mar 24. doi:10.1155/2022/9463314
by admin | Aug 27, 2024 | Mesenchymal Stem Cells, Neurodegenerative Diseases, Stem Cell Research, Stem Cell Therapy
Intrathecal cell delivery has emerged as a promising approach for improving the quality of life for patients with neurological conditions, thanks to previous studies showing its safety and potential benefits.
As part of this review, Mesa Bedoya et al. summarize the findings of a systematic review and meta-analysis aimed at evaluating the safety of intrathecally delivered mesenchymal stem cells (MSCs).
Neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, significantly impact patients’ quality of life and contribute to a substantial global disease burden. With limited treatment options available, MSC therapy has gained attention due to its ability to differentiate into various cell types, secrete growth factors, and provide neuroprotection. MSCs can be delivered through several routes, including intrathecal administration, which allows for direct delivery to the central nervous system (CNS) and has been shown to enhance cell bioavailability near damaged areas.
The authors’ primary goal was to assess the safety of intrathecal MSC administration by analyzing randomized controlled trials (RCTs) comparing this method to control treatments in adult patients with neurological conditions.
As part of this review, Mesa Bedoya et al. conducted a thorough search of several databases up through April 2023, including RCTs that compared intrathecal MSC delivery with control treatments. They focused on adverse events (AEs) and performed a meta-analysis using statistical models to evaluate the overall safety. The authors also examined potential factors influencing the occurrence of AEs and assessed publication bias.
A total of 303 records were reviewed, with nine RCTs involving 540 patients meeting the inclusion criteria. The analysis revealed that intrathecal MSCs were associated with an increased probability of AEs related to musculoskeletal and connective tissue disorders. Specifically, fresh MSCs had a higher probability of causing AEs compared to cryopreserved MSCs. Additionally, multiple doses of MSCs were associated with a 36% reduction in the probability of AEs compared to single doses.
Despite these findings, the data did not show significant associations between AEs and various study covariates. The review highlighted that, while there was a higher incidence of musculoskeletal and connective tissue disorders, no serious adverse events (SAEs) were reported. The most common AEs, which included back pain, pain in extremities, and muscle aches, were generally transient and minimal in risk if patients were monitored appropriately.
Mesa Bedoya et al’s study supports the notion that intrathecal MSC delivery is a generally safe procedure, with an increased risk of specific, minor AEs. It also confirms previous findings that suggest this method is a viable option for delivering MSC therapy to patients with neurological conditions.
However, the authors also acknowledge limitations, including potential small-study effects and issues related to the crossover design of some included trials. These limitations suggest that the results should be interpreted with caution, and the findings highlight the need for larger, well-designed RCTs with longer follow-up periods to validate the safety and efficacy of intrathecal MSC delivery.
The authors conclude that this review indicates that intrathecal delivery of MSCs results in a minor increase in AEs related to musculoskeletal and connective tissue disorders but no serious adverse events. This supports the safety of intrathecal MSC therapy for neurological conditions, though further research with larger sample sizes and more rigorous study designs is needed to confirm these findings and address the limitations identified.
Source: Mesa Bedoya, L.E., Camacho Barbosa, J.C., López Quiceno, L. et al. The safety profile of mesenchymal stem cell therapy administered through intrathecal injections for treating neurological disorders: a systematic review and meta-analysis of randomised controlled trials. Stem Cell Res Ther 15, 146 (2024). https://doi.org/10.1186/s13287-024-03748-7
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