title: Cellular and molecular characterization of human cardiac stem cells reveals key features essential for their function and safety.
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.
authors: 1Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.|2Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors: Sadaf
authors: S
authors: Vahdat
authors: 3Department of Molecular Systems Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Seyed Ahmad
authors: SA
authors: Mousavi
authors: 4Department of Cardiac Surgery, Rajaei Cardiovascular Medical Research Center, Tehran University of Medical Science, Tehran, Iran.
authors: Gholamreza
authors: G
authors: Omrani
authors: 4Department of Cardiac Surgery, Rajaei Cardiovascular Medical Research Center, Tehran University of Medical Science, Tehran, Iran.
authors: Maziar
authors: M
authors: Gholampour
authors: 1Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Fattah
authors: F
authors: Sotoodehnejadnematalahi
authors: 1Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Zaniar
authors: Z
authors: Ghazizadeh
authors: 3Department of Molecular Systems Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Javad
authors: J
authors: Gharechahi
authors: 1Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.|5Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
authors: Hossein
authors: H
authors: Baharvand
authors: 3Department of Molecular Systems Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.|6Department of Systems Biology, Agricultural Biotechnology Research Institute of Iran, Karaj, Iran.
authors: Ghasem Hosseini
authors: GH
authors: Salekdeh
authors: 1Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.|7Department of Regenerative Biomedicine at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors: Nasser
authors: N
authors: Aghdami
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D049109:Cell Proliferation / Q000235:genetics; D002469:Cell Separation; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D019009:Proto-Oncogene Proteins c-kit