Prospective Isolation of ISL1 Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy
Authors: Faranak Fattahi
Daehee Hwang
Sara Taleahmad
Ghasem Hosseini Salekdeh
Sehyun Chae
Parisa Shabani
Jaesuk Lee
Kyunghee Byun
Hananeh Fonoudi
Mehdi Sharifi Tabar
Shahab Mirshahvaladi
Bonghee Lee
Zaniar Ghazizadeh
Nasser Aghdami
Hossein Baharvand
Mehdi Mirzaei
Todd Evans
Delger Bayersaikhan
Paul A Haynes
Journal: Stem Cell Reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cell therapy; myocardial biology; proteomics; stem cells.
Affiliations: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ., 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., Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia; Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia., Center for Regenerative Medicine, Gachon University, Incheon City, Republic of Korea., Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea., Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran., Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia., Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran., Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Regenerative Biomedicine at Cell Science Research, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran., Department of Surgery, Weill Cornell Medicine, New York, NY, USA., Center for Regenerative Medicine, Gachon University, Incheon City, Republic of Korea. Electronic address: ., 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; Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 Figure 5C. * Blue boxes: The Control SAPK JNK and Medium SAPK JNK panels appear to overlap. ![file] , 
 Supplemental Figure S4G: * Yellow boxes: Two panels, representing ALCAM- and ALCAM - + appear to look very similar to each other. ![file] , 
 Dear Dr. Bik, Thank you so much for your analysis of my articles! Currently, we are carefully checking each of your comments and concerns regarding  image concerns and undisclosed conflict of interest in some of my papers. We have also started to contact the related journals to ask for corrective notes on those articles that need correction or other potential actions. We will update, on Pubpeer, the final changes and actions communicated with the journals once we get feedback from the journals. Thank you again for your time and concern! Sincerely yours, Hossein Baharvand , 
 #2 Thank you for your concern. Correspondents have explained to the editor and asked to publish an Erratum to our manuscript to avoid any potential ambiguities in the future and they accepted. , 
 Correction, March 2021: https: www.cell.com stem-cell-reports fulltext S2213-6711(21)00042-4  The authors wish to make the following corrections to Figures 5C and S4G of this article. The authors declare that these mistakes do not affect the results and conclusions of the study. * In Figure 5C, the image designated as belonging to the group u201cMediumu201d (row 1, column 2) was an incorrect image put in by mistake. This has now been replaced in the figure below with the correct merge image. * In Figure S4G, the image designated as belonging to the group u201cALCAM-u201d (row 1, column 3) was also an incorrect image put in by mistake. This has now been replaced in the figure below with the correct merge image as well. ,