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- Title
Isolation, Culture and Characterization of Cardiac Progenitor Cells Derived from Human Embryonic Heart Tubes.
- Authors
Zhang, Xi; Zhang, Chuan-Sen; Liu, Yan-Chun; Yang, Xiang-Qun; Xiong, Shao-Hu; Wen, Yu; Jiang, Er-Peng; Li, Rui; Zhang, Zhi-Ying; Liu, Fang; Ye, Yong
- Abstract
A variety of studies have reported on the isolation and expansion of cardiac stem cells from adult hearts. However, there is little information concerning cardiac stem/progenitor cells derived from embryonic hearts/heart tubes. To provide more evidence for embryonic heart-derived stem/progenitor cells, Nkx2.5+ human cardiac progenitorcells (hCPCs) were isolated and cloned from human heart tubes. The cells stained positive for Nkx2.5 and Oct-4, and negative for α-smooth muscle actin (α-SMA), cytokeratin, factor-VIII, α-sarcomeric actin and c-Kit. GATA-4 expression of Nkx2.5+ hCPCs was higher than that of embryonic limb bud mesenchymal cells of the control group (p < 0.05). These cells were passaged continuously for >3 months (23 passages) and proliferated actively in vitro. After being treated with 5-azacytidine, Nkx2.5+ hCPCs underwent cardiomyogenic differentiation. Ultrastructural observation confirmed that the longitudinal section of these cardiomyogenic differentiation cells clearly revealed typical sarcomeres and intercalated discs. α-MHC, α-sarcomeric actin and GATA-4 levels were increased in Nkx2.5+ hCPCs treated with 5-azacytidine compared to untreated cells. Nkx2.5+ hCPCs exhibited positive staining and had a higher expression for α-SMA when cocultured with canine vascular endothelial cells. After Nkx2.5+ hCPCs were treated with endothelin-1, all cells displayed spontaneous electrical activity and spontaneous beating. Connexin-40 and -45 were stained positive in the treated cells. In conclusion, Nkx2.5+ hCPCs derived from heart tubes have been isolated and cloned in vitro. These cells are capable of long-term self-renewal and possess a potential to differentiate into cardiac muscle-like cells, cardiac pacemaking cells and smooth muscle-like cells. They could have a significant impact on cardiac regeneration medicine and developmental biology.
- Subjects
STEM cells; HEART cells; PROGENITOR cells; MESENCHYMAL stem cells; EMBRYONIC stem cells; CELL proliferation
- Publication
Cells Tissues Organs, 2017, Vol 204, Issue 7, p194
- ISSN
1422-6405
- Publication type
Article
- DOI
10.1159/000204750