Zaniar Ghazizadeh1, Sadaf Vahdat2, Faranak Fattahi3, Hananeh Fonoudi2, Gholamreza Omrani4, Maziar Gholampour4, Nasser Aghdami5. 1. Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. 3. Department of Molecular Systems Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. 4. Department of Cardiac Surgery, Rajaei Cardiovascular Medical Research Center, Tehran, Iran. 5. Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Regenerative Biomedicine at the Cell Science Research, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: Nasser.Aghdami@RoyanInstitute.org.
Abstract
AIMS: Regenerative therapies based on resident human cardiac progenitor cells (hCPCs) are a promising alternative to medical treatments for patients with myocardial infarction. However, hCPCs are rare in human heart and finding efficient source and proper surface marker for isolation of these cells would make them a good candidate for therapy. MAIN METHODS: We have isolated 5.34∗10(6)±2.04∗10(5)/g viable cells from 35 heart tissue samples of 23 patients with congenital heart disease obtained during their heart surgery along with 6 samples from 3 normal subjects during cardiac biopsy. KEY FINDINGS: According to FACS analysis, younger ages, atrial specimen and disease with increased pulmonary vascular resistance were associated with higher percentage of c-kit(+) (CD117) hCPCs. Analysis for other stemness markers revealed increased CD133(+) cells in the hearts of patients with congenital heart disease. By using both immune-labeling and PCR, we demonstrated that these cells express key cardiac lineage and endothelial transcription factors and structural proteins during in vitro differentiation and do express stemness transcription factors in undifferentiated state. Another novel datum of potentially relevant interest is their ability in promoting greater myocardial regeneration and better survival in rat model of myocardial infarction following transplantation. SIGNIFICANCE: Our results could provide evidence for conditions associated with enriched hCPCs in patients with congenital heart disease. Moreover, we showed presence of a significant number of CD133 expressing cardiogenic stem-like cardiac precursors in the heart of patients with congenital heart disease, which could be isolated and stored for future regenerative therapies in these patients.
AIMS: Regenerative therapies based on resident human cardiac progenitor cells (hCPCs) are a promising alternative to medical treatments for patients with myocardial infarction. However, hCPCs are rare in human heart and finding efficient source and proper surface marker for isolation of these cells would make them a good candidate for therapy. MAIN METHODS: We have isolated 5.34∗10(6)±2.04∗10(5)/g viable cells from 35 heart tissue samples of 23 patients with congenital heart disease obtained during their heart surgery along with 6 samples from 3 normal subjects during cardiac biopsy. KEY FINDINGS: According to FACS analysis, younger ages, atrial specimen and disease with increased pulmonary vascular resistance were associated with higher percentage of c-kit(+) (CD117) hCPCs. Analysis for other stemness markers revealed increased CD133(+) cells in the hearts of patients with congenital heart disease. By using both immune-labeling and PCR, we demonstrated that these cells express key cardiac lineage and endothelial transcription factors and structural proteins during in vitro differentiation and do express stemness transcription factors in undifferentiated state. Another novel datum of potentially relevant interest is their ability in promoting greater myocardial regeneration and better survival in rat model of myocardial infarction following transplantation. SIGNIFICANCE: Our results could provide evidence for conditions associated with enriched hCPCs in patients with congenital heart disease. Moreover, we showed presence of a significant number of CD133 expressing cardiogenic stem-like cardiac precursors in the heart of patients with congenital heart disease, which could be isolated and stored for future regenerative therapies in these patients.