Kan Wang, Zhi Jiang, Keith A. Webster, Jinghai Chen, Hengxun Hu, Yu Zhou, Jing Zhao, Lihan Wang, Yingchao Wang, Zhiwei Zhong, Cheng Ni, Qingju Li, Charlie Xiang, Ling Zhang, Rongrong Wu, Wei Zhu, Hong Yu, Xinyang Hu, Jian'an Wang
Abstract
: Our group recently reported positive therapeutic benefit of human endometrium-derived mesenchymal stem cells (EnMSCs) delivered to infarcted rat myocardium, an effect that correlated with enhanced secretion of protective cytokines and growth factors compared with parallel cultures of human bone marrow MSCs (BMMSCs). To define more precisely the molecular mechanisms of EnMSC therapy, in the present study, we assessed in parallel the paracrine and therapeutic properties of MSCs derived from endometrium, bone marrow, and adipose tissues in a rat model of myocardial infarction (MI). EnMSCs, BMMSCs, and adipose-derived MSCs (AdMSCs) were characterized by fluorescence-activated cell sorting (FACS). Paracrine and cytoprotective actions were assessed in vitro by coculture with neonatal cardiomyocytes and human umbilical vein endothelial cells. A rat MI model was used to compare cell therapy by intramyocardial injection of BMMSCs, AdMSCs, and EnMSCs. We found that EnMSCs conferred superior cardioprotection relative to BMMSCs or AdMSCs and supported enhanced microvessel density. Inhibitor studies indicated that the enhanced paracrine actions of EnMSCs were mediated by secreted exosomes. Analyses of exosomal microRNAs (miRs) by miR array and quantitative polymerase chain reaction revealed that miR-21 expression was selectively enhanced in exosomes derived from EnMSCs. Selective antagonism of miR-21 by anti-miR treatment abolished the antiapoptotic and angiogenic effects of EnMSCs with parallel effects on phosphatase and tensin homolog (PTEN), a miR-21 target and downstream Akt. The results of the present study confirm the superior cardioprotection by EnMSCs relative to BMMSCs or AdMSCs and implicates miR-21 as a potential mediator of EnMSC therapy by enhancing cell survival through the PTEN/Akt pathway. The endometrium might be a preferential source of MSCs for cardiovascular cell therapy.
The present report describes the functional and mechanistic comparisons of mesenchymal stem cells (MSCs) from three different sources (bone marrow, adipose, and endometrium) as therapeutic agents for the treatment of cardiovascular disease. MSCs from the endometrium have markedly superior therapeutic potential relative to the other cell types, properties that can be explained by the paracrine actions mediated by exosomal microRNAs, in particular microRNA-21, with downstream effects on cell survival and angiogenesis. The findings are important from a clinical perspective because the endometrium could be a preferential source of MSCs for cardiovascular cell therapy.
This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 June 2025.
All research outputs
#3,061,805
of 30,385,879 outputs
Outputs from Stem Cells Translational Medicine
#344
of 1,692 outputs
Outputs of similar age
#38,350
of 321,075 outputs
Outputs of similar age from Stem Cells Translational Medicine
#18
of 95 outputs
Altmetric has tracked 30,385,879 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,692 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.6. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 321,075 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 95 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.
