Abstract
Cardiosphere-derived cells (CDCs) constitute a cardiac stem cell pool, a promising therapeutics in treating myocardial infarction (MI). However, the cell source of CDCs remains unclear. In this study, we isolated CDCs directly from adult mouse heart epicardium named primary epicardium-derived CDCs (pECDCs), which showed a different expression profile compared with primary epicardial cells (pEpiCs). Interestingly, pECDCs highly expressed T-box transcription factor 18 (Tbx18) and showed multipotent differentiation ability in vitro. Human telomerase reverse transcriptase (hTERT) transduction could inhibit aging-induced pECDCs apoptosis and differentiation, thus keeping a better proliferation capacity. Furthermore, immortalized epicardium CDCs (iECDCs) transplantation extensively promote cardiogenesis in the infracted mouse heart. This study demonstrated epicardium-derived CDCs that may derive from Tbx18+ EpiCs, which possess the therapeutic potential to be applied to cardiac repair and regeneration and suggest a new kind of CDCs with identified origination that may be followed in the developing and injured heart.
Highlights
Cardiosphere-derived cells (CDCs) are a heterogeneous mixture of cardiac cell pools, including cardiac progenitor cells (CPCs), derived from heart biopsy culture [1, 2]
Epicardial cells (EpiCs) located in the heart epicardium from Wt1 immunofluorescence and primary epicardial cells (pEpiCs) isolated from the adult heart epicardium exhibited epithelial cell morphology, which differed from mesenchymal cell morphology of primary epicardium-derived CDCs (pECDCs) (Figure 1B)
Flow cytometry assay (Figure 3B, Supplementary Figure S2) demonstrated that pECDCs uniformly express reported CDC-specific surface markers, transforming growth factor-beta receptor accessory subunit, CD105, and glycosylphosphatidylinositol (GPI)-anchored protein CD90 (Thy-1), while pEpiCs were mostly negative for CD90
Summary
Cardiosphere-derived cells (CDCs) are a heterogeneous mixture of cardiac cell pools, including cardiac progenitor cells (CPCs), derived from heart biopsy culture [1, 2]. CDCs transplantation and paracrine exosomes emerged as a promising therapeutic option for many cardiac diseases including myocardial infarction (MI) [7, 8], dilated cardiomyopathy [9, 10], and dystrophic cardiomyopathy [11, 12]. Many clinical trials have proved the safety and efficiency of autologous and allogeneic CDCs therapy such as the CArdiosphere-Derived aUtologous stem CElls to Reverse ventricUlar dySfunction (CADUCEUS) trial [13], the AutoLogous Human CArdiacDerived Stem Cell to Treat Ischemic cArdiomyopathy (ALCADIA) trial [14], the ALLogeneic
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