Immunosuppressant Drugs Mitigate Immune Responses Generated by Human Mesenchymal Stem Cells Transplanted into the Mouse Parenchyma

Author:

Hwang Jung Won123,Myeong Su Hyeon123,Lee Na-Hee1234,Kim Hyeongseop25,Son Hyo Jin2346,Chang Jong Wook25,Lee Na Kyung246ORCID,Na Duk L.12346

Affiliation:

1. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Gangnam-gu, Seoul, Republic of Korea

2. Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea

3. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

4. Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea

5. Stem Cell Institute, ENCell Co. Ltd., Seoul, Republic of Korea

6. School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea

Abstract

It has been widely accepted that mesenchymal stem cells (MSCs) can evade the immune surveillance of the recipient. However, emerging research cast doubt on whether MSCs are intrinsically immune-privileged. Previously, we observed that the transplantation of human MSCs (hMSCs) into the mouse parenchyma attracted a high infiltration of leukocytes into the injection tract. Thus, in order to reduce the immune responses generated by hMSCs, the aim of this study was to assess which immunosuppressant condition (dexamethasone only, tacrolimus only, or dexamethasone and tacrolimus together) would not only reduce the overall immune response but also enhance the persistence of MSCs engrafted into the caudate putamen of wild-type C57BL/6 mice. According to immunohistochemical analysis, compared to the hMSC only group, the administration of immunosuppressants (for all three conditions) reduced the infiltration of CD45-positive leukocytes and neutrophils at the site of injection. The highest hMSC persistence was detected from the group that received combinatorial administrations of dexamethasone and tacrolimus. Moreover, compared to the immunocompetent WT mouse, higher MSC engraftment was observed from the immunodeficient BALB/c mice. The results of this study support the use of immunosuppressants to tackle MSC-mediated immune responses and to possibly prolong the engraftment of transplanted MSCs.

Funder

Samsung Medical Center

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

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