ISL1 overexpression enhances the survival of transplanted human mesenchymal stem cells in a murine myocardial infarction model

Stem Cell Research & Therapy
Qiuling XiangWeiqiang Li

Abstract

The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed as a marker for cardiovascular progenitor cells. This study investigated whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) improves myocardial infarction (MI) treatment outcomes. The lentiviral vector containing the human elongation factor 1α promoter, which drives the expression of ISL1 (EF1α-ISL1), was constructed using the Multisite Gateway System and used to transduce hMSCs. Flow cytometry, immunofluorescence, Western blotting, TUNEL assay, and RNA sequencing were performed to evaluate the function of ISL1-overexpressing hMSCs (ISL1-hMSCs). The in vivo results showed that transplantation of ISL1-hMSCs improved cardiac function in a rat model of MI. Left ventricle ejection fraction and fractional shortening were greater in post-MI hearts after 4 weeks of treatment with ISL1-hMSCs compared with control hMSCs or phosphate-buffered saline. We also found that ISL1 overexpression increased angiogenesis and decreased apoptosis and inflammation. The greater potential of ISL1-hMSCs may be attributable to an increased number of surviving cells after transplantation. Conditioned medium from ISL1-hMSCs decreased the apoptotic effect of H2O2 o...Continue Reading

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Datasets Mentioned

BETA
PRJNA421054

Methods Mentioned

BETA
PCR
flow cytometry
reverse-transcription PCR
fluorescence-activated cell sorting
FACS
RNA-seq
ELISA

Software Mentioned

ImageJ
Consensus Assessment of Sequence and Variation
FlowJo7
Treestar
HemI Heatmap Illustrator

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