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
by admin | Aug 15, 2024 | Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Liver cirrhosis (LC) is a severe global health problem, contributing to an estimated two million deaths annually. LC results from chronic liver diseases such as hepatitis B and C, alcohol consumption, non-alcoholic fatty liver disease, and autoimmune liver disease. When these diseases progress unchecked, they lead to liver cirrhosis, characterized by inflammation and fibrosis. Most patients with LC die from complications due to a lack of effective treatments and poor patient compliance. While liver transplantation is effective, it is costly and comes with risks like immune rejection and recurrent infections. This has led to an urgent need for alternative treatments for LC.
Mesenchymal stem cells (MSCs) offer a promising alternative due to their ability to renew themselves and differentiate into various cell types. MSCs have gained attention for their potential to treat tissue-damaging diseases due to their low immunogenicity and ability to home to injury sites. Animal studies have shown MSCs to be safe and effective in treating LC, and clinical trials indicate improvements in liver function with no significant adverse effects.
Lu et al.’s study aims to systematically evaluate the efficacy and safety of MSCs for treating liver cirrhosis through a meta-analysis of clinical trials.
As part of this study, the authors analyzed data from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up through May 2023. Researchers used the PICOS principle for literature screening and assessed the risk of bias. Data from each study’s outcome indicators, such as liver function and adverse events, were then extracted and analyzed using Review Manager 5.4.
Eleven clinical trials met the criteria for this analysis. The pooled data showed significant improvements in primary and secondary liver function indicators. Patients who received MSC infusions had higher albumin (ALB) levels at 2 weeks, 1 month, 3 months, and 6 months, and lower MELD scores at 1 month, 2 months, and 6 months compared to the control group. Hepatic arterial injections were particularly effective in improving these scores. Importantly, none of the studies reported severe adverse effects, indicating the safety of MSC therapy.
Key Findings and Recommendations
Considering the findings of this study, the authors provide a number of key findings and recommendations, including:
- Duration of MSC Therapy: The study found that prolonging MSC treatment enhances its effectiveness in end-stage liver disease, improving symptoms such as appetite loss, mental depression, and jaundice.
- Types of MSCs: MSCs can be derived from various tissues, and their effectiveness may vary. Most studies evaluated used bone marrow-derived MSCs (BM-MSCs), which have shown superior therapeutic effects compared to umbilical cord-derived MSCs (UC-MSCs). However, more research is needed to determine the best type of MSC for treating LC.
- Routes of Administration: Different transplantation methods can impact the efficacy of MSC therapy. The hepatic artery route was found to be the most effective, likely due to better MSC homing to the liver. However, this method has clinical limitations such as high surgical risk. Intravenous administration, while safer, was less effective. The authors call for further research to optimize the administration route.
- Secondary Indicators: While primary indicators like MELD score and ALB levels showed significant improvements, secondary indicators such as ALT, AST, TBIL, and INR did not show significant differences between the MSC and control groups. The authors believe this could be due to variability in disease cause, patient population, and follow-up duration.
- Complications and Prognosis: MSC therapy also showed potential in reducing LC complications, such as portal hypertension and ascites, and decreasing mortality and hepatocellular carcinoma (HCC) incidence. However, more clinical trials are needed to confirm these findings and assess the long-term prognosis of MSC therapy in LC.
Lu et al. conclude that mesenchymal stem cell therapy is a safe and effective treatment for liver cirrhosis, significantly improving liver function without severe adverse effects. However, to fully realize the potential of MSC therapy, a standardized treatment protocol is needed. This includes optimizing the timing, dosage, frequency, and administration route of MSC infusions.
Additionally, MSC-derived exosomes show promise as an alternative treatment strategy. The authors call for further research, including multicenter, large-scale, long-term RCTs, to address these questions and improve the therapeutic outcomes for LC patients.
Source: Zhao, Y., Liu, Y., Zhang, W., Li, H., & Wang, L. “Efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis: A systematic review and meta-analysis.” Stem Cell Research & Therapy, 2023. https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03518-x.
by admin | Apr 4, 2024 | Diabetes, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
According to the World Health Organization, an estimated 422 million people worldwide have diabetes. Numerous studies have demonstrated that people with diabetes are at an increased risk of developing both acute and chronic pancreatitis, which increases the risk of developing pancreatic cancer.
Considering the lack of effective therapeutic options for pancreatitis and the limited treatment options for diabetes, researchers have recently turned to the potential of using mesenchymal stem cells (MSCs) as alternative therapeutic treatment options for these conditions.
In this review, Scuteri and Monfrini evaluate the different uses of MSCs for both the treatment of diabetes and the reduction of diabetes-related disease development.
According to the authors, MSCs offer several advantages, including the ability to be isolated from different tissues in a simple way, the ability to be easily harvested and expanded in vitro, and the absence of ethical problems associated with harvesting and use.
In addition, MSCs demonstrate the ability to differentiate, release soluble factors, and migrate toward lesions and sites of inflammation. Considering that inflammation and apoptosis are significant etiopathological factors of diabetes and pancreatitis, Scuteri and Monfrini indicate that MSCs are excellent candidates for regenerative medicine purposes.
In the case of MSCs and diabetes, research has demonstrated that differentiation of MSCs into insulin-releasing cells has been demonstrated in vitro after direct contact with pancreatic islets; the release of anti-inflammatory and antioxidant factors has improved the engraftment and prolonged the survival of transplanted pancreatic islets; and inhibited the apoptotic pathways triggered by endoplasmic reticulum stress in transplanted pancreatic islets. In analyzing this research, the authors conclude that the potential exists for the safe and effective use of MSCs for treatment of diabetes.
Although there has been growing interest in exploring the potential of MSCs on pancreatitis, there have only been a few studies exploring this therapeutic option. In these studies, the presence of MSCs was observed to reduce fibrosis and parenchymal damage by reducing proinflammatory factor expression.
In regard to MSCs and pancreatic cancer, since diabetes and pancreatitis are risk factors for the development of pancreatic cancer and considering MSCs have been found to hold potential as a therapeutic option for these diseases, using MSCs to interrupt the flow of factors leading to the development of pancreatic cancer should lower the incidence of diabetes-related pancreatic cancers.
The authors conclude that MSCs are a very promising therapeutic option for the treatment of diabetes, pancreatitis, and pancreatic cancer.
Source: “Progress in exosomes and their potential use in ocular diseases.” 18 Sep. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459212/.
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