RGD Reference Report - ISL1 overexpression enhances the survival of transplanted human mesenchymal stem cells in a murine myocardial infarction model. - Rat Genome Database

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

Authors: Xiang, Qiuling  Liao, Yan  Chao, Hua  Huang, Weijun  Liu, Jia  Chen, Haixuan  Hong, Dongxi  Zou, Zhengwei  Xiang, Andy Peng  Li, Weiqiang 
Citation: Xiang Q, etal., Stem Cell Res Ther. 2018 Feb 26;9(1):51. doi: 10.1186/s13287-018-0803-7.
RGD ID: 243048463
Pubmed: PMID:29482621   (View Abstract at PubMed)
PMCID: PMC5828309   (View Article at PubMed Central)
DOI: DOI:10.1186/s13287-018-0803-7   (Journal Full-text)

BACKGROUND: 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.
METHODS: 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).
RESULTS: 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 on the cardiomyocyte cell line H9c2. To clarify the molecular basis of this finding, we employed RNA sequencing to compare the apoptotic-related gene expression profiles of control hMSCs and ISL1-hMSCs. The results showed that insulin-like growth factor binding protein 3 (IGFBP3) was the only gene in ISL1-hMSCs with a RPKM value higher than 100 and that the difference fold-change between ISL1-hMSCs and control hMSCs was greater than 3, suggesting that IGFBP3 might play an important role in the anti-apoptosis effect of ISL1-hMSCs through paracrine effects. Furthermore, the expression of IGFBP3 in the conditioned medium from ISL1-hMSCs was almost fourfold greater than that in conditioned medium from control hMSCs. Moreover, the IGFBP3 neutralization antibody reversed the apoptotic effect of ISL1-hMSCs-CM.
CONCLUSIONS: These results suggest that overexpression of ISL1 in hMSCs promotes cell survival in a model of MI and enhances their paracrine function to protect cardiomyocytes, which may be mediated through IGFBP3. ISL1 overexpression in hMSCs may represent a novel strategy for enhancing the effectiveness of stem cell therapy after MI.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ISL1Humanmyocardial infarction amelioratesIDA  RGD 
Isl1Ratmyocardial infarction amelioratesISOISL1 (Homo sapiens) RGD 
Isl1Mousemyocardial infarction amelioratesISOISL1 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Isl1  (ISL LIM homeobox 1)

Genes (Mus musculus)
Isl1  (ISL1 transcription factor, LIM/homeodomain)

Genes (Homo sapiens)
ISL1  (ISL LIM homeobox 1)

Additional Information