Advantages and challenges of stem cell therapy for osteoarthritis (Review).
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ABSTRACT:
SUBMITTER: Loo SJQ
PROVIDER: S-EPMC8212446 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Autoimmune liver disease (AILD) is a series of chronic liver diseases with abnormal immune responses, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The treatment options for AILD remain limited, and the adverse side effects of the drugs that are typically used for treatment frequently lead to a low quality of life for AILD patients. Moreover, AILD patients may have a poor prognosis, especially those with an incomplete response to first-line treatment. Mesenchymal stem cells (MSCs) are pluripotent stem cells with low immunogenicity and can be conveniently harvested. MSC-based therapy is emerging as a promising approach for treating liver diseases based on their advantageous characteristics of immunomodulation, anti-fibrosis effects, and differentiation to hepatocytes, and accumulating evidence has revealed the positive effects of MSC therapy in AILD. In this review, we first summarize the mechanisms, safety, and efficacy of MSC treatment for AILD based on work in animal and clinical studies. We also discuss the challenges of MSC therapy in clinical applications. In summary, although promising data from preclinical studies are now available, MSC therapy is currently far for being applied in clinical practice, thus developing MSC therapy in AILD is still challenging and warrants further research.
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Project description:Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.
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Project description:Intra-striatal transplantation of homotypic fetal tissue at the time of peak striatal neurogenesis can provide some functional benefit to patients suffering from Huntington's disease. Currently, the only approach shown to slow down the course of this condition is replacement of the neurons primarily targeted in this disorder, although it has been transient and has only worked with a limited number of patients. Otherwise, this dominantly inherited neurodegenerative disease inevitably results in the progressive decline of motricity, cognition, and behavior, and leads to death within 15 to 20 years of onset. However, fetal neural cell therapy of Huntington's disease, as with a similar approach in Parkinson's disease, is marred with both technical and biological hurdles related to the source of grafting material. This heavily restricts the number of patients who can be treated. A substitute cell source is therefore needed, but must perform at least as well as fetal neural graft in terms of brain recovery and reconstruction, while overcoming its major obstacles. Human pluripotent stem cells (embryonic in origin or induced from adult cells through genetic reprogramming) have the potential to meet those challenges. In this review, the therapeutic potential in view of 4 major issues is identified during fetal cell therapy clinical trials: 1) logistics of graft procurement, 2) quality control of the cell preparation, 3) immunogenicity of the graft, and 4) safety of the procedure.
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Project description:Administration of mesenchymal stem cells (MSCs) to diseased hearts improves cardiac function and reduces scar size. These effects occur via the stimulation of endogenous repair mechanisms, including regulation of immune responses, tissue perfusion, inhibition of fibrosis, and proliferation of resident cardiac cells, although rare events of transdifferentiation into cardiomyocytes and vascular components are also described in animal models. While these improvements demonstrate the potential of stem cell therapy, the goal of full cardiac recovery has yet to be realized in either preclinical or clinical studies. To reach this goal, novel cell-based therapeutic approaches are needed. Ongoing studies include cell combinations, incorporation of MSCs into biomaterials, or pre-conditioning or genetic manipulation of MSCs to boost their release of paracrine factors, such as exosomes, growth factors, microRNAs, etc. All of these approaches can augment therapeutic efficacy. Further study of the optimal route of administration, the correct dose, the best cell population(s), and timing for treatment are parameters that still need to be addressed in order to achieve the goal of complete cardiac regeneration. Despite significant progress, many challenges remain.
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