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Prospective Isolation of Isl1+ Cardiac Progenitors From Human Escs for Myocardial Infarction Therapy Publisher Pubmed



Ghazizadeh Z1, 2 ; Fattahi F3, 13 ; Mirzaei M4, 5, 6 ; Bayersaikhan D7 ; Lee J7 ; Chae S8 ; Hwang D8 ; Byun K7 ; Tabar MS3 ; Taleahmad S3 ; Mirshahvaladi S3 ; Shabani P1 ; Fonoudi H1 ; Haynes PA4 Show All Authors
Authors
  1. Ghazizadeh Z1, 2
  2. Fattahi F3, 13
  3. Mirzaei M4, 5, 6
  4. Bayersaikhan D7
  5. Lee J7
  6. Chae S8
  7. Hwang D8
  8. Byun K7
  9. Tabar MS3
  10. Taleahmad S3
  11. Mirshahvaladi S3
  12. Shabani P1
  13. Fonoudi H1
  14. Haynes PA4
  15. Baharvand H1, 9
  16. Aghdami N1, 10
  17. Evans T11
  18. Lee B7
  19. Salekdeh GH3, 12
Show Affiliations
Authors Affiliations
  1. 1. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  2. 2. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran, Iran
  4. 4. Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia
  5. 5. Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
  6. 6. Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia
  7. 7. Center for Regenerative Medicine, Gachon University, Incheon City, South Korea
  8. 8. Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, South Korea
  9. 9. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran
  10. 10. Department of Regenerative Biomedicine at Cell Science Research, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  11. 11. Department of Surgery, Weill Cornell Medicine, New York, NY, United States
  12. 12. Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia
  13. 13. Department of Biochemistry and Biophysics, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, School of Medicine, University of California, San Francisco, United States

Source: Stem Cell Reports Published:2018


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. 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