The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy.

Dahai Hu,Haijun Wang,Xiaowen Huang,Jun Zhang,Xiaoyan Liu,Tao Zhang,Yunchuan Wang

doi:10.1186/s13287-015-0240-9

Abstract

Mesenchymal stem cells (MSCs) are ideal for cell-based therapy in various inflammatory diseases because of their immunosuppressive and tissue repair properties. Moreover, their immunosuppressive properties and low immunogenicity contribute to a reduced or weakened immune response elicited by the implantation of allogeneic MSCs compared with other cell types. Therefore, implantation of allogeneic MSCs may be a promising cell-based therapy. In this review, we first summarize the unique advantages of allogeneic MSCs for therapeutic applications. Second, we critically analyze the factors influencing their therapeutic effects, including administration routes, detection time-points, disease models, differentiation of MSCs in vivo, and timing and dosage of MSC administration. Finally, current approaches to allogeneic MSC application are discussed. In conclusion, allogeneic MSCs are a promising option because of their low immunogenicity and immunosuppressive and tissue repair capabilities. Further investigations are needed to enhance the consistency and efficacy of MSCs when used as a cell-based therapy in inflammatory diseases as well as for tissue repair.

Highlights

Mesenchymal stem cells (MSCs) are classified into various groups according to the cell source, such as bone marrow-derived mesenchymal stem cell (MSC) (BM-MSCs), adipose-derived MSCs (ASCs), and umbilical cord MSCs
We describe in detail the factors that influence the therapeutic effects of allo-MSCs below
We find that the presence of immunogenicity after differentiation decreases the therapeutic effects of allo-MSCs, it does not indicate the definite loss of protective effects immediately, which is consistent with previous reports [40, 41]

Summary

Introduction

Mesenchymal stem cells (MSCs) are classified into various groups according to the cell source, such as bone marrow-derived MSCs (BM-MSCs), adipose-derived MSCs (ASCs), and umbilical cord MSCs. The use of various disease models may be one reason for the controversy about the protective effects of allo-MSCs. Differentiation of MSCs in vivo versus therapeutic effects The low immunogenicity of MSCs does not ensure they are fully immune privileged in an in vivo setting. Timing of MSC administration versus therapeutic effect The immune status of a recipient before and after allograft organ transplantation determines the survival of implanted allo-MSCs. Crop et al [42] reported that, before kidney transplantation, recipient peripheral blood mononuclear cells (PBMCs) did not lyse allo-MSCs, but that PBMCs isolated 3, 6, and 12 months after transplantation showed increasing ability to lyse allo-MSCs. In vivo experiments have shown that the different timing of auto-MSC transplantation determines their therapeutic effect in a myocardial infarction model [43]. MSCs attenuated acute immune rejection in renal transplantation, and had the potential benefit of reducing the dosage of the conventional immunosuppressant, tacrolimus [49]

Method

Conclusion and future perspectives