Faculty Opinions recommendation of Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.

Abstract Background: Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear. Methods: HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function, angiogenesis, fibrosis and hypertrophy, and immune cells infiltration were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4+ T cells migration. Results: HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4+ T cells and CD4+FoxP3+ regulatory T cells in the heart with HucMSC than that with N.S treatment on day 7 post MI. In addition, the protein level of C-C Motif Chemokine Ligand 5 (CCL5) greatly increased in the HucMSCs treated heart compared to the control. In vitro, HucMSCs inhibited CD4+ T cells migration and addition of CCL5 antibody or C-C Motif Chemokine receptor 5 (CCR5) antagonist significantly reversed this effect. Conclusion: These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4+FoxP3+ regulatory T cells and contributed to the migration of CD4+ T cells into the injured heart via CCL5/CCR5 pathway.

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Human Umbilical Cord Mesenchymal Stem Cells Alleviate Myocardial Endothelial-Mesenchymal Transition in a Rat Dilated Cardiomyopathy Model

Transplantation Proceedings ◽

10.1016/j.transproceed.2019.01.080 ◽

2019 ◽

Vol 51 (3) ◽

pp. 936-941

Author(s):

C. Zhang ◽

Y. Zhou ◽

X. Lai ◽

G. Zhou ◽

H. Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Dilated Cardiomyopathy ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Mesenchymal Transition ◽

Endothelial Mesenchymal Transition

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Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the Akt/Sfrp2 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1958941 ◽

2019 ◽

Vol 2019 ◽

pp. 1-19 ◽

Cited By ~ 9

Author(s):

Jing Ni ◽

Xijun Liu ◽

Yiheng Yin ◽

Peiyu Zhang ◽

Ya-Wei Xu ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cardiac Function ◽

Umbilical Cord ◽

Rat Model ◽

Therapeutic Option ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Ecm Remodeling

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exoTIMP2) on the MI rat model. The huc-exoTIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exoTIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFβ-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exoTIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exoTIMP2, indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects. Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.

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