Prospective isolation of ISL1+ cardiac progenitors from human ESCs for myocardial infarction therapy

Zaniar Ghazizadeh*, Faranak Fattahi, Mehdi Mirzaei, Delger Bayersaikhan, Jaesuk Lee, Sehyun Chae, Daehee Hwang, Kyunghee Byun, Mehdi Sharifi Tabar, Sara Taleahmad, Shahab Mirshahvaladi, Parisa Shabani, Hananeh Fonoudi, Paul A. Haynes, Hossein Baharvand, Nasser Aghdami, Todd Evans, Bonghee Lee, Ghasem Hosseini Salekdeh

*Corresponding author for this work

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Pages (from-to)848-859
Number of pages12
JournalStem Cell Reports
Volume10
Issue number3
DOIs
Publication statusPublished - 13 Mar 2018

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Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • cell therapy
  • myocardial biology
  • proteomics
  • stem cells

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