通过 PTX3 稳定 TSG6 可提高 CD317MSCs 的治疗一致性和疗效。

Improved therapeutic consistency and efficacy of CD317 MSCs through stabilizing TSG6 by PTX3.

机构信息

Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen Zhongshan Obstetrics & Gynecology Hospital, Fuqiang Avenue 1001, Shenzhen, 518060, Guangdong, People's Republic of China.

Guangdong Engineering Technology Research Center of Reproductive Immunology for Peri-Implantation, Shenzhen, 518000, People's Republic of China.

出版信息

Stem Cell Res Ther. 2024 Mar 27;15(1):92. doi: 10.1186/s13287-024-03706-3.

DOI:10.1186/s13287-024-03706-3

PMID:38539221

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10976765/

Abstract

BACKGROUND

Previously, we have demonstrated that the batch variations of human platelet lysate (conventional MSC expansion medium) induce MSC heterogeneity and therapeutic inconsistency. On the other hand, the MSCs expanded with chemical defined medium have improved therapeutic consistency.

METHODS

In the current study, we studied the MSC subpopulation composition and variation in different types and batches of MSC expansion medium with scRNA-seq analysis.

RESULTS

MSCs expanded with different batches of media have higher levels of heterogeneity from the perspective of cell subpopulation composition at transcriptome levels and therapeutic inconsistency. The CD317 subpopulation has enhanced immune suppression activities. And the percentage of CD317 MSCs within MSCs is tightly correlated with its immune suppression activities, and also contributes to the heterogeneity and therapeutic inconsistency of MSCs. the CD317 MSCs have increased expression levels of PTX3, which might stabilize the TSG6 protein and improve the therapeutic effects CONCLUSIONS: Thus, purifying CD317 MSCs is one efficient strategy to reduce MSC heterogeneity and increase the therapeutic consistency of MSCs.

摘要

背景

此前，我们已经证明，人血小板裂解液（传统 MSC 扩增培养基）的批次差异会导致 MSC 异质性和治疗效果不一致。另一方面，用化学成分确定的培养基扩增的 MSC 具有更好的治疗一致性。

方法

在本研究中，我们通过 scRNA-seq 分析研究了不同类型和批次的 MSC 扩增培养基中 MSC 亚群组成和变化。

结果

从转录组水平的细胞亚群组成和治疗效果不一致的角度来看，用不同批次培养基扩增的 MSC 具有更高的异质性。CD317 亚群具有增强的免疫抑制活性。而 MSC 中 CD317 MSC 的百分比与它的免疫抑制活性密切相关，也导致了 MSC 的异质性和治疗效果不一致。CD317 MSC 具有更高水平的 PTX3 表达，这可能稳定 TSG6 蛋白并提高治疗效果。