Cellular and molecular characterization of human cardiac stem cells reveals key features essential for their function and safety

Sadaf Vahdat, Seyed Ahmad Mousavi, Gholamreza Omrani, Maziar Gholampour, Fattah Sotoodehnejadnematalahi, Zaniar Ghazizadeh, Javad Gharechahi, Hossein Baharvand, Ghasem Hosseini Salekdeh, Nasser Aghdami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Cell therapy of heart diseases is emerging as one of the most promising known treatments in recent years. Transplantation of cardiac stem cells (CSCs) may be one of the best strategies to cure adult or pediatric heart diseases. As these patient-derived stem cells need to be isolated from small heart biopsies, it is important to select the best isolation method and CSC subpopulation with the best cardiogenic functionality. We employed three different protocols including c-KIT+ cell sorting, clonogenic expansion, and explants culture to isolate c-KIT+ cells, clonogenic expansion-derived cells (CEDCs), and cardiosphere-derived cells (CDCs), respectively. Evaluation of isolated CSC characteristics in vitro and after rat myocardial infarction (MI) model transplantation revealed that although c-KIT+ and CDCs had higher MI regenerative potential, CEDCs had more commitment into cardiomyocytes and needed lower passages that were essential to reach a definite cell count. Furthermore, genome-wide expression analysis showed that subsequent passages caused changes in characteristics of cells, downregulation of cell cycle-related genes, and upregulation of differentiation and carcinogenic genes, which might lead to senescence, commitment, and possible tumorigenicity of the cells. Because of different properties of CSC subpopulations, we suggest that appropriate CSCs subpopulation should be chosen based on their experimental or clinical use.

Original languageEnglish
Pages (from-to)1390-1404
Number of pages15
JournalStem Cells and Development
Volume24
Issue number12
DOIs
Publication statusPublished - 15 Jun 2015
Externally publishedYes

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