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

通过 PTX3 稳定 TSG6 来提高 CD317+ MSCs 的治疗一致性和疗效

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作者:Shaoquan Shi #, Si Chen #, Bowei Liang #, Yumeng Li, Qi Ma, Meiqi Li, Jingting Zhang, Lan Yao, Jianyong Xu

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.

Conclusions

Thus, purifying CD317+ MSCs is one efficient strategy to reduce MSC heterogeneity and increase the therapeutic consistency of MSCs.

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.

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