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HLA-A2增强脐带血间充质干细胞对高氧肺损伤的治疗效果。

HLA-A2 Promotes the Therapeutic Effect of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Hyperoxic Lung Injury.

作者信息

Kwak Jihye, Choi Wankyu, Bae Yunkyung, Kim Miyeon, Choi Soojin, Oh Wonil, Jin Hyejin

机构信息

Biomedical Research Institute, MEDIPOST Co., Ltd., Gyeonggi-do 463-400, Korea.

出版信息

Bioengineering (Basel). 2022 Apr 18;9(4):177. doi: 10.3390/bioengineering9040177.

DOI:10.3390/bioengineering9040177
PMID:35447737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9029550/
Abstract

Mesenchymal stem cells (MSCs) are one of the most extensively studied stem cell types owing to their capacity for differentiation into multiple lineages as well as their ability to secrete regenerative factors and modulate immune functions. However, issues remain regarding their further application for cell therapy. Here, to demonstrate the superiority of the improvement of MSCs, we divided umbilical cord blood-derived MSCs (UCB-MSCs) from 15 donors into two groups based on efficacy and revealed donor-dependent variations in the anti-inflammatory effect of MSCs on macrophages as well as their immunoregulatory effect on T cells. Through surface marker analyses (242 antibodies), we found that HLA-A2 was positively related to the anti-inflammatory and immunoregulatory function of MSCs. Additionally, HLA-A2 mRNA silencing in MSCs attenuated their therapeutic effects in vitro; namely, the suppression of LPS-stimulated macrophages and phytohemagglutinin-stimulated T cells. Moreover, HLA-A2 silencing in MSCs significantly decreased their therapeutic effects in a rat model of hyperoxic lung damage. The present study provides novel insights into the quality control of donor-derived MSCs for the treatment of inflammatory conditions and diseases.

摘要

间充质干细胞（MSCs）是研究最为广泛的干细胞类型之一，这是因为它们能够分化为多种细胞谱系，还具备分泌再生因子和调节免疫功能的能力。然而，在其进一步应用于细胞治疗方面仍存在一些问题。在此，为了证明改进后的间充质干细胞的优越性，我们根据功效将来自15名供体的脐带血间充质干细胞（UCB-MSCs）分为两组，并揭示了间充质干细胞对巨噬细胞的抗炎作用及其对T细胞的免疫调节作用存在供体依赖性差异。通过表面标志物分析（242种抗体），我们发现HLA-A2与间充质干细胞的抗炎和免疫调节功能呈正相关。此外，间充质干细胞中HLA-A2 mRNA的沉默减弱了它们在体外的治疗效果；也就是说，抑制了脂多糖刺激的巨噬细胞和植物血凝素刺激的T细胞。而且，间充质干细胞中HLA-A2的沉默显著降低了它们在高氧肺损伤大鼠模型中的治疗效果。本研究为用于治疗炎症性病症和疾病的供体来源间充质干细胞的质量控制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/7aca0a4e7acd/bioengineering-09-00177-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/6f89338950a5/bioengineering-09-00177-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/0f2eaf7bd391/bioengineering-09-00177-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/6df579bab46a/bioengineering-09-00177-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/c51c1cc1b1ab/bioengineering-09-00177-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/a498a7330a62/bioengineering-09-00177-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/7aca0a4e7acd/bioengineering-09-00177-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/6f89338950a5/bioengineering-09-00177-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/0f2eaf7bd391/bioengineering-09-00177-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/6df579bab46a/bioengineering-09-00177-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/c51c1cc1b1ab/bioengineering-09-00177-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/a498a7330a62/bioengineering-09-00177-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240a/9029550/7aca0a4e7acd/bioengineering-09-00177-g006.jpg

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