Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for…

DOI: https://doi.org/10.1016/j.stemcr.2018.01.037

ZaniarGhazizadeh, FaranakFattahi, MehdiMirzaei, DelgerBayersaikhan, JaesukLee ,SehyunChae, DaeheeHwang, KyungheeByun, Mehdi SharifiTabar, SaraTaleahmad, ShahabMirshahvaladi, ParisaShabani, HananehFonoudi, Paul A.Haynes, HosseinBaharvand, NasserAghdami, ToddEvans, BongheeLee, Ghasem Hosseini Salekdeh

abstract

he 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.

Keywords: cell therapy, proteomics, myocardial biology, stem cells