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免疫抑制剂药物减轻移植到小鼠实质内的人骨髓间充质干细胞引发的免疫反应。

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

机构信息

Department of Health Sciences and Technology, SAIHST, 35019Sungkyunkwan University, Gangnam-gu, Seoul, Republic of Korea.

Stem Cell & Regenerative Medicine Institute, 36626Samsung Medical Center, Seoul, Republic of Korea.

出版信息

Cell Transplant. 2021 Jan-Dec;30:9636897211019025. doi: 10.1177/09636897211019025.

DOI:10.1177/09636897211019025
PMID:34044601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8168027/
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.

摘要

人们普遍认为间充质干细胞(MSCs)可以逃避受体的免疫监视。然而,新的研究对 MSCs 是否具有内在的免疫特权提出了质疑。先前,我们观察到将人 MSCs(hMSCs)移植到小鼠实质中会吸引大量白细胞浸润到注射部位。因此,为了减少 hMSCs 引发的免疫反应,本研究旨在评估哪种免疫抑制条件(仅地塞米松、仅他克莫司、或地塞米松和他克莫司联合)不仅会降低整体免疫反应,而且会增强移植到野生型 C57BL/6 小鼠尾状核中的 MSCs 的持久性。根据免疫组织化学分析,与 hMSC 单独组相比,免疫抑制剂(所有三种条件)的给药减少了注射部位 CD45 阳性白细胞和中性粒细胞的浸润。从接受地塞米松和他克莫司联合给药的组中检测到最高的 hMSC 持久性。此外,与免疫功能正常的 WT 小鼠相比,从免疫缺陷的 BALB/c 小鼠中观察到更高的 MSC 植入率。这项研究的结果支持使用免疫抑制剂来解决 MSC 介导的免疫反应,并可能延长移植的 MSCs 的植入时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/26e445292b8f/10.1177_09636897211019025-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/96610be81487/10.1177_09636897211019025-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/4173d802033c/10.1177_09636897211019025-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/7aaa9618ac22/10.1177_09636897211019025-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/829c69a157ca/10.1177_09636897211019025-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/ae7740bc3c5c/10.1177_09636897211019025-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/856933f24225/10.1177_09636897211019025-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/26e445292b8f/10.1177_09636897211019025-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/96610be81487/10.1177_09636897211019025-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/4173d802033c/10.1177_09636897211019025-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/7aaa9618ac22/10.1177_09636897211019025-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/829c69a157ca/10.1177_09636897211019025-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/ae7740bc3c5c/10.1177_09636897211019025-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/856933f24225/10.1177_09636897211019025-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1150/8168027/26e445292b8f/10.1177_09636897211019025-fig7.jpg

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