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

PLoS One. 2022 Jun 16;17(6):e0269985. doi: 10.1371/journal.pone.0269985. eCollection 2022.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Flow Cytometry
  • Heart Failure* / metabolism
  • Humans
  • Myocytes, Cardiac* / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism

Substances

  • Antigens, CD34
  • Proto-Oncogene Proteins c-kit

Grants and funding

This study was funded by grants from the Swedish Society of Medicine (JS, https://www.sls.se/); The Gothenburg Society of Medicine (MS, JS, https://goteborgslakaresallskap.se/); the Emelle Foundation (MS); the Heart-Lung Foundation (LMH, https://www.hjart-lungfonden.se/); ALF research grant from the Sahlgrenska University Hospital (JS, LMH, https://www.sahlgrenska.se/); grants from the foundations of the Sahlgrenska University Hospital (MS, JS, https://www.sahlgrenska.se/) and University of Skövde (JSy, https://www.his.se), by grants from the Swedish Knowledge Foundation (https://www.kks.se). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.