Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated cardiac protection
- Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong (China)
- School of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong (China)
- Department of Health Sciences Research & Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ 85259 (United States)
- Institute of Molecular and Cellular Biology, Biopolis (Singapore)
Bone marrow-derived mesenchymal stem cells (BM-MSCs) contribute to myocardial repair after myocardial infarction (MI) by secreting a panel of growth factors and cytokines. This study was to investigate the potential mechanisms of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS) in regulation of the profiles of BM-MSCs secretion and compare the therapeutic efficacy of NUCKS{sup -/-} and wide type-BM-MSCs (WT-BM-MSCs) on MI. The secretion profiles between NUCKS{sup -/-} and WT-BM-MSCs under hypoxia (1%O{sub 2}) were analyzed. Gene function analysis showed that compared with WT-BM-MSCs-conditioned medium (CdM), some genes over-presented in NUCKS{sup -/-}BM-MSCs-CdM were closely associated with inflammatory response, regulation of cell proliferation, death, migration and secretion. Notably, VEGFa in NUCKS{sup -/-}BM-MSCs-CdM was higher than that of WT-BM-MSCs-CdM. WT-BM-MSCs and NUCKS{sup -/-}BM-MSCs were transplanted into the peri-infarct region in mice of MI. At 4 weeks after cell transplantation, NUCKS{sup -/-} or WT-BM-MSCs group significantly improved heart function and vessels density and reduced infarction size and apoptosis of cardiomyocytes. Furthermore, NUCKS{sup -/-}BM-MSCs provided better cardioprotective effects than WT-BM-MSCs against MI. Our study demonstrates that depletion of NUCKS enhances the therapeutic efficacy of BM-MSCs for MI via regulating the secretion. - Highlights: • Absence of NUCKS alters the secretion of BM-MSCs and enhances VEGFa level. • Absence of NUCKS in BM-MSCs exerts a better therapeutic effect for myocardial infarction than WT-BM-MSCs. • The enhanced cardioprotection of NUCKS{sup -/-}BM-MSCs is attributed to the increased capacity of angiogenesis and anti-apoptosis post transplantation.
- OSTI ID:
- 22738134
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 356; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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