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Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy
- Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy
- Ghazizadeh, Z.; Fattahi, F.; Mirzaei, M.; Bayersaikhan, D.; Lee, J.; Chae, Se Hyun; Hwang, Dae Hee; Byun, K.; Tabar, M.S.; Taleahmad, S.; Mirshahvaladi, S.; Shabani, P.; Fonoudi, H.; Haynes, P.A.; Baharvand, H.; Aghdami, N.; Evans, T.; Lee, B.; Salekdeh, G.H.
- DGIST Authors
- Hwang, Dae Hee
- Issue Date
- Stem Cell Reports, 10(3), 848-859
- Article Type
- cell therapy; myocardial biology; proteomics; stem cells
- The LIM-homeodomain transcription factor ISL1 marks multipotent cardiac progenitors that give rise to cardiac muscle, endothelium, and smooth muscle cells. ISL1+ progenitors can be derived from human pluripotent stem cells, but the inability to efficiently isolate pure populations has limited their characterization. Using a genetic selection strategy, we were able to highly enrich ISL1+ cells derived from human embryonic stem cells. Comparative quantitative proteomic analysis of enriched ISL1+ cells identified ALCAM (CD166) as a surface marker that enabled the isolation of ISL1+ progenitor cells. ALCAM+/ISL1+ progenitors are multipotent and differentiate into cardiomyocytes, endothelial cells, and smooth muscle cells. Transplantation of ALCAM+ progenitors enhances tissue recovery, restores cardiac function, and improves angiogenesis through activation of AKT-MAPK signaling in a rat model of myocardial infarction, based on cardiac MRI and histology. Our study establishes an efficient method for scalable purification of human ISL1+ cardiac precursor cells for therapeutic applications. In this article, Salekdeh and colleagues show that ISL1+ cardiac progenitors can be purified from a heterogeneous population of hESC-derived cardiomyocytes using ALCAM. Transplantation of multipotent ISL1+/ALCAM+ progenitors enhances tissue recovery, restores cardiac function, and improves angiogenesis in a rat model of myocardial infarction, based on cardiac MRI and histology. © 2018 The Authors
- Cell Press
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- Department of New BiologySystems Biology and Medicine Lab1. Journal Articles
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