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/.
by admin | Mar 14, 2024 | Spinal Cord Injury, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Nerve damage resulting from spinal cord injury (SCI) often leads to temporary or permanent loss of function and contributes to poor quality of life. Most common among males below 30 years of age, SCI recovery has been limited specifically as a result of the low growth capacity of neurons and a lack of nerve growth factors.
While current SCI treatment focuses on stabilizing the injured area and preventing secondary injury through a combination of surgery, pharmacological intervention, and rehabilitation, the success of treatment has been limited and unable to stimulate spinal cord regeneration.
Considering the limited success of confidential SCI treatments, several types of stem cells are currently being tested for the treatment of SCI, including mesenchymal stem cells (MSCs) isolated from bone marrow (BMSCs), umbilical cord (UC-MSCs), and adipose tissue (ADSCs).
In this review, Liau et al. discuss the current status of MSC therapy for SCI, criteria to consider when applying MSC therapy, and review novel biological therapies that can be used together with MSC therapy to enhance its therapeutic potential.
Based on the results of clinical trials, the authors conclude that MSC therapy is beneficial for SCI patients. While not all patients responded to MSC therapy, the authors note that observed improvement varied from patient to patient. In addition to discrepancies attributed to patient variations, source of MSC, route of stem cell administration, timing of cell administration, number of cell administrations, number of cells administered, and cell preparation methods were also observed to affect the efficacy of therapy.
Despite the delayed progress in phase III trials, there are several new therapeutic treatment strategies that incorporate stem cell secretory product-based therapy, including stem cell secretome therapy, scaffold-based therapy, and immunotherapy. The authors indicate that all of these novel therapeutic approaches may be able to be used in combination with MSC therapy to enhance the therapeutic efficacy of MSCs by improving cell survival, migration, engraftment, and proliferation.
The authors conclude this review by summarizing that, to date, MSC therapy has been demonstrated to be safe but unable to improve neurological function for all treated patients. Despite the limited success of this therapy, other studies are currently underway in an effort to improve the delivery of MSCs and MSC-derived products by utilizing scaffolds or by combining them with immunotherapy to improve the efficacy of the treatment.
Source: “Treatment of spinal cord injury with mesenchymal stem cells – NCBI.” 22 Sep. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510077/.
by admin | Mar 7, 2024 | Spinal Cord Injury, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Spinal cord injuries (SCI) are the most serious complication associated with spinal injuries and often result in permanent damage to the nervous system. With nearly 300,000 people in the United States living with SCI, the inability to treat these injuries has a significant impact on physical, mental, and financial health.
Additionally, while 94% of those suffering acute traumatic SCI survive initial treatment for the condition, both long-term survival and quality of life are often reduced as a result of post-injury complications. Further complicating the issue is the fact that the current standard of SCI treatment is designed only to reduce the secondary effects of injury and not directly promote healing through neuroregeneration.
Considering that mesenchymal stem cells (MSCs) are known to have anti-inflammatory properties, promote vascular regeneration, and to release neuro-nutrients, they are becoming increasingly promising as a potential treatment for SCI.
In this article, Xia et al. examine the evidence of pathophysiological changes occurring after SCI, review the underlying mechanisms of MSCs, summarize the potential application of MSCs in clinical practice, and highlight the challenges surrounding the use of MSCs in the treatment of SCI in future applications.
The goal of any SCI therapeutic treatment option is to promote rapid recovery of neurological function through a combination of medical and surgical interventions. However, to date, there are no optimal treatment strategies that allow for this goal to be met.
MSCs’ multidirectional differentiation capabilities are highly viable and known to provide structural support in SCI. In terms of using MSCs in the treatment of SCI, and specifically for their role as an anti-inflammatory agent, the most attractive aspect is their unique immunomodulatory ability.
Additionally, the goal of treatment after SCI is to repair the damaged nerve cells and restore nerve function. Studies exploring differentiation of MSCs after SCI have demonstrated spontaneously expressed neuromarkers at SCI sites and have allowed for recovery of neurological function.
The authors point out that traumatic SCI usually results in the direct destruction of blood vessels around the spinal cord which often results in ischemic necrosis and secondary injuries. Since promoting vascular recovery contributes to the recovery of motor function in patients with SCI, SCI vascular recovery is a new target for the treatment of SCI. Several studies have observed that MSCs secrete angiogenic factors that promote pericyte recruitment, a critical step in vascular maturation. The authors also report recent findings indicating that 57% of the vascular endothelial cells around the SCI of a mouse showed vascular regeneration effects after receiving MSC-EVs with an extensive vascular network formed around the injury over a period of 28 days.
Although MSCs are beneficial to the recovery of neurological function in patients with SCI, the authors call for additional research to focus on better understanding the SCI cellular mechanisms and MSC action for use in clinical practice. Additionally, Xia et al. point out that the survival rate and long-term survival of MSCs in the SCI microenvironment remain an unresolved issue.
MSCs repair SCI through anti-inflammatory effects and by promoting nerve axon regeneration and vascular regeneration. While further research is required to fully understand the mechanism underlying the effect of MSCs, the authors conclude the role of MSCs in treating SCI has been demonstrated in several clinical trials.
Source: “Mesenchymal stem cells in the treatment of spinal cord injury.”
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1141601/full.
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