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Title 

Heterogeneous niche activity of Ex-Vivo expanded MSCs as factor for variable outcomes in hematopoietic recovery

Authors 

J H KimH S LeeH K ChoiJ A KimIn-Sun ChuS H LeemI H Oh

Publisher 

Public Library of Science

Issue Date 

2016

Citation 

Plos One, vol. 11, no. 12, pp. e0168036-e0168036

Abstract 

Ex-vivo expanded mesenchymal stromal cells (MSCs) are increasingly used for paracrine support of hematopoietic stem cell (HSC) regeneration, but inconsistent outcomes have hindered ongoing clinical trials. Here, we show that significant heterogeneity in the niche activity of MSCs is created during their culture in various serum-supplemented media. The MSCs cultured under stimulatory or non-stimulatory culture conditions exhibited differences in colony forming unit-fibroblast contents, expression levels of cross-talk molecules (Jagged-1 and CXCL-12) and their support for HSC self-renewal. Accordingly, the enhancing effects of MSCs on hematopoietic engraftment were only visible when HSCs were co-transplanted with MSCs under stimulatory conditions. Of note, these differences in MSCs and their effects on HSCs were readily reversed by switching the cultures, indicating that the difference in niche activity can be caused by distinct functional state, rather than by clonal heterogeneity. Supporting the findings, transcriptomic analysis showed distinct upstream signaling pathways such as inhibition of P53 and activation of ER-stress response gene ATF4 for MSCs under stimulatory conditions. Taken together, our study shows that the niche activity of MSCs can vary rapidly by the extrinsic cues during culture causing variable outcomes in hematopoietic recoveries, and point to the possibility that MSCs can be prescreened for more predictable efficacy in various cell therapy trials.

ISSN 

1932-6203

Link 

http://dx.doi.org/10.1371/journal.pone.0168036

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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