Prospective Isolation of ISL1(+) Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy
- Authors
- Ghazizadeh, Zaniar; Fattahi, Faranak; Mirzaei, Mehdi; Bayersaikhan, Delger; Lee, Jaesuk; Chae, Sehyun; Hwang, Daehee; Byun, Kyunghee; Tabar, Mehdi Sharifi; Taleahmad, Sara; Mirshahvaladi, Shahab; Shabani, Parisa; Fonoudi, Hananeh; Haynes, Paul A.; Baharvand, Hossein; Aghdami, Nasser; Evans, Todd; Lee, Bonghee; Salekdeh, Ghasem Hosseini
- Issue Date
- 13-Mar-2018
- Publisher
- CELL PRESS
- Keywords
- cell therapy; myocardial biology; proteomics; stem cells
- Citation
- STEM CELL REPORTS, v.10, no.3, pp.848 - 859
- Journal Title
- STEM CELL REPORTS
- Volume
- 10
- Number
- 3
- Start Page
- 848
- End Page
- 859
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3971
- DOI
- 10.1016/j.stemcr.2018.01.037
- ISSN
- 2213-6711
- Abstract
- 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 identifiedALCAM( 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.
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