Challenges and advances in clinical applications of mesenchymal stromal cells

Abstract

Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.

Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Improve Ovarian Function and Proliferation of Premature Ovarian Insufficiency by Regulating the Hippo Signaling Pathway

“…Over 300 clinical trials involving MSC therapies have been completed, and some results have shown MSCs exhibit therapeutic effects in various disorders. Meanwhile, 15 clinical trials of EVs have been registered in ClinicalTrial.gov (38). If proved to be effective, MSC-and EV-based therapies will be available for clinical applications in the future.…”

[Retracted] Mesenchymal Stem Cell‐Derived Exosomes and Their Potential Agents in Hematological Diseases

“…MSCs are multipotent non-hematopoietic stem cells and have been intensely investigated for clinical applications within the last decades [ 16 , 45 , 46 ]. Since their first discovery from bone marrow by the Russian haematologist Friedenstein in 1970s [ 47 ], MSCs have been isolated from numerous tissues and various organs like bone marrow (BM), umbilical cord, placenta, amniotic fluid, adipose, dental pulp, and induced pluripotent stem cells (iPSCs) or human embryonic stem cells (ESCs) ( Figure 1(a) ) [ 45 , 48 ]. To better study this population, it is of paramount importance to identify the phenotypes and characteristics of primary MSCs.…”

“…Since no single biomarker is specific for the precise identification, the International Society for Cellular Therapy established the minimum but widely accepted criteria in 2006 [ 46 , 49 ]: (i) plastic-adherent stromal cells with self-renewal capability; (ii) immunophenotype strongly positive for a cluster of surface makers CD105, CD73, and CD90, while negative for CD45, CD34, CD14, CD11b, and CD19 ( Figure 1(b) ) and (iii) multipotency with osteogenic, chondrogenic, adipogenic, and myogenic differentiation potential ( Figure 1(c) ). Nevertheless, MSCs are far from being a uniform cell type and inherited heterogeneities exist in different subsets [ 45 , 49 ], which makes these criteria insufficient to standardize MSCs [ 50 ].…”

Mesenchymal Stem Cells in Premature Ovarian Insufficiency: Mechanisms and Prospects

“…In Korea, an MSC product (Cartistem ® ) was approved for treatment of osteoarthritis, and this novel product is safe and effective ( Park et al, 2017 ). In addition, other various MSC products from different sources have been approved for treatment of various diseases ( Zhou et al, 2021 ).…”