Cardioprotective effects of genetically engineered cardiac stem cells by spheroid formation on ischemic cardiomyocytes

Abstract

Background: Sca-1+ cardiac stem cells and their limited proliferative potential were major limiting factors for use in various studies. Methods: Therefore, the effects of sphere genetically engineered cardiac stem cells (S-GECS) inserted with telomerase reverse transcriptase (TERT) were investigated to examine cardiomyocyte survival under hypoxic conditions. GECS was obtained from hTERT-immortalized Sca-1+ cardiac stem cell (CSC) lines, and S-GECS were generated using poly-HEMA.Results: The optimal conditions for S-GECS was determined to be 1052 GECS cells/mm 2 and a 48 h culture period to produce spheroids. Compared to adherent-GECS (A-GECS) and S-GECS showed significantly higher mRNA expression of SDF-1α and CXCR4. S-GECS conditioned medium (CM) significantly reduced the proportion of early and late apoptotic cardiomyoblasts during CoCl 2 -induced hypoxic injury; however, gene silencing via CXCR4 siRNA deteriorated the protective effects of S-GECS against hypoxic injury. As downstream pathways of SDF-1α/CXCR4, the Erk and Akt signaling pathways were stimulated in the presence of S-GECS CM. S-GECS transplantation into a rat acute myocardial infarction model improved cardiac function and reduced the fibrotic area. These cardioprotective effects were confirmed to be related with the SDF-1α/CXCR4 pathway. Conclusions: Our findings suggest that paracrine factors secreted from transplanted cells may protect host cardiomyoblasts in the infarcted myocardium, contributing to beneficial left ventricle (LV) remodeling after acute myocardial infarction (AMI).

Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease

“…Scaffold-free approaches using spheroids in hanging drop cultures provide similar advantages to EHTs and do not require the addition of foreign material for the fabrication of the cardiac tissue [ 88 , 101 ]. For instance, Jeong et al’s [ 102 ] research showed that genetically engineered antigen-1-positive cardiac stem cells (Sca-1 + CSC lines) secrete paracrine factors such as SDF-1α and have cardioprotective roles described using in vitro spheroids. SDF-1α has demonstrated to protect the ischemic cardiomyocytes by inducing the signaling pathway for cell growth, survival, and protein synthesis in the 3D IRI spheroid heart model [ 102 ].…”

Unravelling the Biology of Adult Cardiac Stem Cell-Derived Exosomes to Foster Endogenous Cardiac Regeneration and Repair

“…Indeed, both allogeneic mesenchymal stem cells and cardiac stem cells, alone or in combination have been tested in preclinical models with positive results and also reached the first-in-man clinical experimentation [43][44][45]. The latter has created the path for the idea of creating "supercargo cells", which is transplantable cellular reservoirs engineered to release multiple cardioprotective and cardio-regenerative factors or small molecules to obtain effective myocardial regeneration [45,46].…”

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“…5(a) depicts ZnO nanorod growth on seed layers containing grains with several sizes. Since the c-axis is well known as the fastest-growing direction of the hexagonal wurtzite ZnO phase, [27][28][29][30][31] Zn 2+ and OHin a solution are consumed to form ZnO nanorods on the c-plane oriented surfaces on grains. As seen in a SEM image (The second image in Fig.…”