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.

Keywords: Mesenchymal stem cells (MSCs); genetic manipulation; potential risks; preconditioning.

Figure 1

The summary of MSCs mechanisms of therapy. IL, interleukins; IFNγ, interferon-γ; TNF-α, tumor necrosis factor α; TGF, transforming growth factor; BD, beta defensins; EGF, epidermal growth factor; IGF, insulin like growth factor; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; SDF-1, stromal cell-derived factor 1; Ang, Angiopoietin; MCP, monocyte chemoattractant protein; GM-CSF, granulocyte-macrophage colony-stimulating factor; IDO, indoleamine 2,3-dioxygenase; NO, nitric oxide; PGE2, prostaglandin E2; LL37, human cathelicidin.

Figure 2

Analysis of the percentages of some common diseases registered for MSC-based cell therapy. Data Retrieved from Clinical Trials.gov (2016). This pie chart illustrates the broad distribution of clinical studies evaluating the efficacy and safety of target indications. The three main indications for MSC-based cell therapy are autoimmune diseases, cardiovascular diseases and neuro-degenerative diseases, respectively. Sine autoimmune diseases indications are the largest group at 25%, the widely held trials rely on the cells immune modulatory properties. GvHD, Graft-versus-Host Disease; MS, multiple sclerosis; CD, Crohn’s disease; T1D, type1 diabetes; SLE, systemic lupus erythematous; RA, rheumatoid arthritis.