“…TSG6 is involved in the therapeutic effects of MSCs in treating IBD, such as mucosal barrier recovery through activating endogenous stem cells [ 96 – 99 ], and immune modulation [ 49 , 50 , 97 , 100 – 102 ]. Lacking TSG6 makes mice more vulnerable to IBD development, resulting from dysregulated HA deposit [ 50 , 103 ]. In addition, TSG6 stimulates a macrophage phenotypic shift from M1 to M2, having an important role in alleviating DSS-induced colitis [ 50 , 100 ].…”
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.
“…TSG6 is involved in the therapeutic effects of MSCs in treating IBD, such as mucosal barrier recovery through activating endogenous stem cells [ 96 – 99 ], and immune modulation [ 49 , 50 , 97 , 100 – 102 ]. Lacking TSG6 makes mice more vulnerable to IBD development, resulting from dysregulated HA deposit [ 50 , 103 ]. In addition, TSG6 stimulates a macrophage phenotypic shift from M1 to M2, having an important role in alleviating DSS-induced colitis [ 50 , 100 ].…”
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.
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