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A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies.

ABSTRACT: Multipotent mesenchymal stem cells (MSCs) have been considerably inspected as effective tool for cell-based therapy of inflammatory, immune-mediated, and degenerative diseases, attributed to their immunomodulatory, immunosuppressive, and regenerative potentials. In the present review, we focus on recent research findings of the clinical applications and therapeutic potential of this cell type, MSCs' mechanisms of therapy, strategies to improve their therapeutic potentials such as manipulations and preconditioning, and potential/unexpected risks which should be considered as a prerequisite step before clinical use. The potential risks would probably include undesirable immune responses, tumor formation and the transmission of incidental agents. Then, we also review some of the milestones in the field, briefly discuss challenges and highlight the new guideline suggested for future directions and perspectives.

SUBMITTER: Saeedi P

PROVIDER: S-EPMC6789202 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies.

Saeedi Pardis P Halabian Raheleh R Imani Fooladi Abbas Ali AA

Stem cell investigation 20190925

Multipotent mesenchymal stem cells (MSCs) have been considerably inspected as effective tool for cell-based therapy of inflammatory, immune-mediated, and degenerative diseases, attributed to their immunomodulatory, immunosuppressive, and regenerative potentials. In the present review, we focus on recent research findings of the clinical applications and therapeutic potential of this cell type, MSCs' mechanisms of therapy, strategies to improve their therapeutic potentials such as manipulations a ...[more]

PMID: 31620481

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Project description:Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is the result of the body's own immune cells being auto-reactive to the myelin regions of the body as if these regions were foreign antigens. This demyelination process is damaging to the electrical conductivity of neurons. The current medicines are only capable of fighting off the symptoms of the disease, but not the disease itself. Specialized stem cells, known as mesenchymal stem cells (MSCs), seem to be the candidate therapy to get rid of MS. MSCs can be isolated from multiple sources of the person's body, and even from the umbilical cord (UC) and placenta of a donor. These cells have anti-inflammatory effects so they can target the overactivity and self-antigen attacks by T cells and macrophages; this immune system overactivity is characteristic of MS. MSCs show the ability to locate into brain lesions when injected and thus can compensate for the loss of the brain function by differentiating into neuronal precursor cells and glial cells. The author has listed tables of clinical trials that have utilized MSCs from different sources, along with the years and the phase of study completed for each trial. The consensus is that these cells work on inhibiting CD4+ and CD8+ T cell activation, T regulatory cells (Tregs), and macrophage switch into the auto-immune phenotype. The best source of MSCs seems to be the UC due to the easiness of extraction, the noninvasive method of collection, their higher expansion ability and more powerful immune-modulating properties compared to other locations in the body. Studies showed there was a significant decline of mRNA expression of several cytokines after the administration of MSCs derived from the UC (UCMSCs). Other researchers were able to repair the defects of Tregs in MS patients by co-culturing Tregs from these patients with UCMSCs, which decreased the production of the pro-inflammatory cytokine IFN γ , and also suggested a strong link between Tregs lack of functionality in MS patients with the pathogenesis of the disease.

Project description:Background:The therapeutic capacity of mesenchymal stem cells (also known as mesenchymal stromal cells/MSCs) depends on their ability to respond to the need of the damaged tissue by secreting beneficial paracrine factors. MSCs can be genetically engineered to express certain beneficial factors. The aim of this systematic review is to compile and analyze published scientific literatures that report the use of engineered MSCs for the treatment of various diseases/conditions, to discuss the mechanisms of action, and to assess the efficacy of engineered MSC treatment. Methods:We retrieved all published studies in PubMed/MEDLINE and Cochrane Library on July 27, 2019, without time restriction using the following keywords: "engineered MSC" and "therapy" or "manipulated MSC" and "therapy." In addition, relevant articles that were found during full text search were added. We identified 85 articles that were reviewed in this paper. Results:Of the 85 articles reviewed, 51 studies reported the use of engineered MSCs to treat tumor/cancer/malignancy/metastasis, whereas the other 34 studies tested engineered MSCs in treating non-tumor conditions. Most of the studies reported the use of MSCs in animal models, with only one study reporting a trial in human subjects. Thirty nine studies showed that the expression of beneficial paracrine factors would significantly enhance the therapeutic effects of the MSCs, whereas thirty three studies showed moderate effects, and one study in humans reported no effect. The mechanisms of action for MSC-based cancer treatment include the expression of "suicide genes," induction of tumor cell apoptosis, and delivery of cytokines to induce an immune response against cancer cells. In the context of the treatment of non-cancerous diseases, the mechanism described in the reviewed papers included the expression of angiogenic, osteogenic, and growth factors. Conclusion:The therapeutic capacity of MSCs can be enhanced by inducing the expression of certain paracrine factors by genetic modification. Genetically engineered MSCs have been used successfully in various animal models of diseases. However, the results should be interpreted cautiously because animal models might not perfectly represent real human diseases. Therefore, further studies are needed to explore the translational potential of genetically engineered MSCs.

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A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies.

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A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies.

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