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 | Oct 25, 2024 | Exosomes, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Respiratory diseases are a major global health concern, responsible for millions of deaths each year. Conditions like chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and pneumonia claim many lives annually, and despite advancements in medical research, there is still no cure for many of these diseases. Current treatments typically focus on managing symptoms and slowing disease progression, but there is growing interest in stem cell (SC) therapy as a potential game-changer for treating lung diseases.
Stem cell therapy is a type of regenerative medicine where stem cells, which have the ability to regenerate or repair damaged tissues, are introduced into the body. There are four main sources of stem cells: embryonic tissues, fetal tissues, adult tissues (like mesenchymal stem cells or MSCs), and genetically manipulated somatic cells, known as induced pluripotent stem cells (iPSCs). Numerous studies have shown that stem cell therapies could be safe and effective for a variety of lung diseases, including COPD, ARDS, and pulmonary fibrosis.
Researchers are increasingly focusing on a cell-free approach that uses stem cell-derived exosomes (SC-Exos). Exosomes are small particles that stem cells release into the body to help with intercellular communication. These exosomes contain beneficial properties of stem cells, including immunomodulatory, anti-inflammatory, and antifibrotic effects.
SC-Exos offer several advantages over stem cell therapy. They have a unique ability to inherit the molecular patterns of their parent stem cells, which means they can potentially mimic the therapeutic effects of stem cells.
Several studies have demonstrated that SC-Exos may be particularly useful for treating respiratory diseases. For example, preclinical and clinical studies have explored the potential of SC-Exos for treating COVID-19, an illness that severely impacts the respiratory system. SC-Exos have been shown to help reduce the severity of complications, such as pneumonia and ARDS, by modulating the immune system and reducing inflammation. In one clinical trial, the use of SC-Exos from bone marrow-derived mesenchymal stem cells (BMSCs) improved survival rates, oxygenation, and immune system regulation in patients.
To deliver SC-Exos effectively, researchers have explored various methods, including intratracheal instillation (direct delivery into the lungs via a tube) and inhalation through nebulizers. Inhalation has shown particular promise, as it allows the exosomes to directly reach the affected lung tissues. In one study involving a mouse model of lung injury caused by the bacterium Pseudomonas aeruginosa, inhaling MSC-derived exosomes significantly improved survival rates. Clinical trials are currently underway to determine if similar results can be achieved in humans.
While many studies attribute the benefits of SC-Exos to their RNA content, it is likely that other components of exosomes also play important roles in their therapeutic effects. Further research is needed to better understand these mechanisms and to optimize the use of exosomes in clinical practice.
Another area of research is focused on developing synthetic or “exosome-mimic” particles that could replicate the therapeutic effects of natural exosomes. These particles could be designed to contain the key bioactive molecules responsible for the beneficial effects of SC-Exos, while being easier and cheaper to produce. However, creating these synthetic particles will require extensive research to ensure they are safe and effective.
Looking ahead, researchers are optimistic about the future of SC-Exos as a potential treatment for respiratory diseases. As our understanding of exosome biology continues to grow, it is likely that we will see more clinical trials and eventually the development of new therapies based on exosome technology. In particular, the use of aerosolized SC-Exos delivered via inhalation holds great promise for treating lung diseases, as it allows the exosomes to directly target damaged tissues in the lungs.
Azhdari et. al conclude that SC-Exos represent an exciting new frontier in the treatment of respiratory diseases. With further research and development, they could offer a powerful new tool for managing and potentially curing conditions like COPD, ARDS, and pulmonary fibrosis, providing hope to millions of patients around the world.
Source: Azhdari MH, Goodarzi N, Doroudian M, MacLoughlin R. Molecular Insight into the Therapeutic Effects of Stem Cell-Derived Exosomes in Respiratory Diseases and the Potential for Pulmonary Delivery. International Journal of Molecular Sciences. 2022; 23(11):6273. https://doi.org/10.3390/ijms23116273
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 20, 2024 | Multiple Sclerosis, Neural Stem Cells, Stem Cell Research, Stem Cell Therapy
Multiple sclerosis (MS) is a long-term inflammatory disease that affects the central nervous system (CNS) of an estimated 3 million people worldwide. Characterized by the loss of the protective covering (myelin) of nerve fibers and degeneration of the nerve fibers themselves, MS damage disrupts communication between the brain and the rest of the body. Most MS patients start with a form known as relapsing-remitting MS (RRMS), where symptoms flare up at intervals and then partially or fully improve. Typical symptoms during these flare-ups include lack of muscle control, fatigue, and sensory impairments.
As the disease progresses, many individuals transition from RRMS to a progressive form of MS. Progressive MS is marked by a steady decline in function and an accumulation of disabilities, rather than periodic attacks. Unfortunately, the treatment options for progressive MS (PMS) are limited and often ineffective. The few available medications can help with active forms of PMS but are generally poor at slowing down the disease’s progression or promoting repair of damaged tissues.
The Promise of Stem Cell Therapy
Stem cell therapy has emerged as a promising approach to addressing the needs of patients with PMS. Stem cells have the unique ability to develop into various types of cells and offer several potential benefits, including providing support to nerve cells, modulating the immune system, and even replacing damaged cells. These characteristics make stem cells an attractive option for treating the complex pathology of PMS.
Current State of Stem Cell Therapy Research
In this review, Smith et al. explore the current state of preclinical and clinical evidence supporting the use of stem cells in treating PMS and discuss prospective hurdles impeding their translation into revolutionary regenerative medicines.
According to the authors, preclinical studies suggest that stem cells might help by reducing inflammation and protecting nerve cells in the CNS. However, translating these findings into effective treatments for humans remains a challenge.
Existing disease-modifying therapies (DMTs) have improved the treatment of RRMS by targeting the immune system to prevent the attacks that cause demyelination and nerve damage. These therapies work well for RRMS because they address the inflammatory processes that drive the disease. Unfortunately, as patients transition to the progressive phase of MS, conventional DMTs become less effective. PMS is characterized by a different set of pathological processes, including persistent inflammation behind a closed blood-brain barrier and activation of microglia (the brain’s immune cells) rather than T and B cells.
Stem Cell Therapy’s Potential Benefits
According to Smith et al. stem cell therapy offers potential benefits in several ways, including
- Neuroprotection: Stem cells can potentially protect nerve cells from damage and death, which is crucial in progressive forms of MS.
- Immunomodulation: Stem cells might help modulate the immune system, reducing harmful inflammation that contributes to disease progression.
- Cell Replacement: Stem cells have the potential to replace damaged cells and promote the repair of damaged tissues.
While these potential benefits are compelling, the authors have found that the effectiveness of stem cell therapy in PMS is still largely unproven in clinical settings. The majority of current stem cell research focuses on the relapsing forms of MS or other diseases, with fewer studies dedicated specifically to PMS.
Current Status and Future Prospects
Stem cell therapy has demonstrated safety and feasibility across different types of cells and administration methods. The most promising results so far have been in studies involving neural stem cells (NSCs), which have shown potential in preclinical models for reducing chronic neuroinflammation. However, substantial clinical research is needed to validate these findings and determine the practical benefits of stem cell therapy for PMS.
The authors conclude that while stem cell therapy holds considerable promise for treating progressive multiple sclerosis, more research is needed. Future studies should focus on large, well-designed clinical trials to assess the benefits and risks of stem cell treatments. If proven effective, Smith et al. believe that stem cell therapy could become a revolutionary treatment for PMS and offer hope to millions of patients affected by this debilitating condition.
Source: Smith JA, Nicaise AM, Ionescu RB, Hamel R, Peruzzotti-Jametti L, Pluchino S. Stem Cell Therapies for Progressive Multiple Sclerosis. Front Cell Dev Biol. 2021;9:696434. Published 2021 Jul 9. doi:10.3389/fcell.2021.696434
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 | Aug 3, 2024 | ALS, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease that affects motor neurons in the brain and spinal cord, leading to muscle paralysis and death, typically within 3-5 years of onset. Despite two FDA-approved therapies, Riluzole, and Edravarone, which offer limited benefits, there remains no cure for ALS.
Considering this, researchers have turned to Mesenchymal Stem Cells (MSCs), which have shown promise in animal models and preliminary human trials for neurodegenerative diseases, including ALS.
Understanding ALS and MSC Therapy
ALS is characterized by the rapid degeneration of motor neurons, leading to muscle paralysis. The exact cause of ALS is complex and not fully understood. About 10% of cases are familial, while 90% are sporadic. Existing treatments only modestly slow disease progression and extend survival by a few months.
Stem cells, particularly MSCs, have shown potential in neuroprotection and immunomodulation. MSCs can be derived from various sources, including bone marrow, adipose tissue, embryonic tissue, cord blood, reprogrammed mature cells, and perinatal tissue. They support hematopoiesis and produce mesodermal cells. MSCs have demonstrated immunomodulatory and neurotrophic effects in animal models and early human trials.
As part of this study, Petrou et al. aimed to evaluate the safety and efficacy of repeated spinal injections of autologous MSCs in ALS patients. This open-label clinical trial included patients aged 20-70, with definite ALS diagnoses and ALS Functional Rating Scale Revised (ALSFRS-R) scores above 20. The patients received 1-4 intrathecal MSC injections at intervals of 3-6 months, with safety and tolerability as primary endpoints, and efficacy as secondary endpoints.
This trial found no serious adverse events, demonstrating the safety of repeated MSC injections. As evidence, the authors point out that, 15 out of 19 patients showed a reduction in the progression rate of their ALSFRS-R scores by more than 25% between the first and second injections, with an average improvement of 107.1%. Similar improvements were observed between subsequent injections. Thirteen patients experienced a 25% improvement in their progression rate over the entire treatment period, with an average improvement of 47.4%. Seven patients showed clinical improvement after the first transplantation, and five remained improved after the second cycle. These benefits were correlated with the intervals between the injections, suggesting that regular MSC administrations might be crucial for sustained efficacy.
Previous Studies on MSCs in ALS
Several small, open-label clinical trials have suggested that MSC treatment can be beneficial for neurological diseases, including ALS. In a phase I/II trial by the same research group, ALS patients received intrathecal and intravenous MSC injections, which were safe and showed a trend toward disease stabilization over six months. Another phase I/II and IIa trial with Brainstorm® used modified MSCs producing neurotrophic factors (MSC-NTF), showing at least a 25% improvement in disease progression, particularly in the intrathecally treated group.
Additional trials, including a randomized, placebo-controlled phase II study, demonstrated mixed results. While some trials noted improvements in a subgroup of rapid progressors, others did not show significant differences between MSC-treated and placebo groups overall. These studies highlight the need for repeated injections to maintain the benefits of MSC therapy.
Implications From the Current Study
According to Petrou et al., repeated intrathecal injections of MSCs over a longer follow-up period appears to induce significant, but short-term, clinical improvements and slow disease progression in a majority of patients. This study also reaffirmed the safety profile of MSC, with only mild and transient adverse events observed.
The study highlights the potential of MSC therapy in providing neuroprotection and slowing ALS progression. The immunomodulatory effects of MSCs, possibly reducing inflammation in the central nervous system, may also contribute to their therapeutic benefits. However, the small sample size and open-label design are limitations, necessitating larger, controlled trials to confirm these findings.
Future Directions
Petrou et al. concluded that repeated intrathecal injections of autologous MSCs are safe for ALS patients and suggest potential medium-term clinical benefits. However, larger studies are needed to confirm these findings. The consistent observation of safety and indications of efficacy across multiple cycles of treatment is encouraging, indicating that MSC therapy could slow the progression of ALS and improve patients’ quality of life.
The study’s promising results support the continued exploration of MSC therapy for ALS. The authors call for future trials to focus on optimizing the timing and frequency of MSC injections to maximize clinical benefits. Larger, controlled studies are essential to validate these findings and potentially establish MSC therapy as a viable treatment option for ALS. By addressing the unmet needs in neuroprotection and immunomodulation, MSC therapy holds the potential of improving the quality of life and survival for ALS patients.
Source: Panayiota Petrou, Ibrahim Kassis, Nour Eddine Yaghmour, Ariel Ginzberg, Dimitrios Karussis. A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis. Front. Biosci. (Landmark Ed) 2021, 26(10), 693–706. https://doi.org/10.52586/4980
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