Human intracardiac SSEA4+CD34 cells show features of cycling, immature cardiomyocytes and are distinct from Side Population and C-kit+CD45- cells

• Published in: PloS one Vol. 17; no. 6; p. e0269985
• Main Authors: Sandstedt, Mikael, Vukusic, Kristina, Ulfenborg, Benjamin, Jonsson, Marianne, Mattsson Hultén, Lillemor, Dellgren, Göran, Jeppsson, Anders, Synnergren, Jane, Sandstedt, Joakim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.06.2022; Public Library of Science (PLoS)
• Subjects: Analysis; Antigens; Bioinformatics; Bioinformatik; Biology and Life Sciences; Biopsy; c-Kit protein; Cardiac; cardiac muscle cell; Cardiomyocytes; CD34; CD34 antigen; CD45 antigen; Cell and Molecular Biology; cell culture; Cell cycle; cell differentiation; cell isolation; cell maturation; cell population; Cell proliferation; cell selection; cell self-renewal; Cell- och molekylärbiologi; Cells; Complications and side effects; Congestive heart failure; controlled study; Cultured; Cycles; endothelial progenitor cell; Failure analysis; Flow cytometry; Genotype & phenotype; Heart cells; Heart failure; Hospitals; human; human cell; Humans; Markers; Medicine and Health Sciences; metabolism; Muscles; Myocytes; Organ donors; Patient outcomes; phenotype; Phenotypes; physiology; Population; Populations; Progenitor cells; protein expression; Proto-Oncogene Proteins c-kit; receptor type tyrosine protein phosphatase C; Research and Analysis Methods; signal transduction; Smooth muscle; stage specific embryo antigen 4; stem cell factor; stem cell factor receptor; Stem cells; Transplantation of organs, tissues, etc; Sweden; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0269985

Cardiomyocyte proliferation has emerged as the main source of new cardiomyocytes in the adult. Progenitor cell populations may on the other hand contribute to the renewal of other cell types, including endothelial and smooth muscle cells. The phenotypes of immature cell populations in the adult human heart have not been extensively explored. We therefore investigated whether SSEA4+CD34- cells might constitute immature cycling cardiomyocytes in the adult failing and non-failing human heart. The phenotypes of Side Population (SP) and C-kit+CD45- progenitor cells were also analyzed. Biopsies from the four heart chambers were obtained from patients with end-stage heart failure as well as organ donors without chronic heart failure. Freshly dissociated cells underwent flow cytometric analysis and sorting. SSEA4+CD34- cells expressed high levels of cardiomyocyte, stem cell and proliferation markers. This pattern resembles that of cycling, immature, cardiomyocytes, which may be important in endogenous cardiac regeneration. SSEA4+CD34- cells isolated from failing hearts tended to express lower levels of cardiomyocyte markers as well as higher levels of stem cell markers. C-kit+CD45- and SP CD45- cells expressed high levels of endothelial and stem cell markers-corresponding to endothelial progenitor cells involved in endothelial renewal.