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

doi:10.1016/j.stemcr.2018.01.037

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 journal › Article › peer-review

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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 language	English
Pages (from-to)	848-859
Number of pages	12
Journal	Stem Cell Reports
Volume	10
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2018.01.037
Publication status	Published - 13 Mar 2018

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.

Correction: 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 (2021) Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy, Stem Cell Reports, Volume 16, Issue 3, Pages 666-668. https://doi.org/10.1016/j.stemcr.2021.01.012.

Keywords

cell therapy
myocardial biology
proteomics
stem cells

Access to Document

10.1016/j.stemcr.2018.01.037

Publisher version (open access)Final published version, 4.68 MBLicence: CC BY-NC-ND

Cite this

Ghazizadeh, Z., Fattahi, F., Mirzaei, M., Bayersaikhan, D., Lee, J., Chae, S., Hwang, D., Byun, K., Tabar, M. S., Taleahmad, S., Mirshahvaladi, S., Shabani, P., Fonoudi, H., Haynes, P. A., Baharvand, H., Aghdami, N., Evans, T., Lee, B., & Salekdeh, G. H. (2018). Prospective isolation of ISL1⁺ cardiac progenitors from human ESCs for myocardial infarction therapy. Stem Cell Reports, 10(3), 848-859. https://doi.org/10.1016/j.stemcr.2018.01.037

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title = "Prospective isolation of ISL1+ cardiac progenitors from human ESCs for myocardial infarction therapy",

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.",

keywords = "cell therapy, myocardial biology, proteomics, stem cells",

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

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. Correction: 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 (2021) Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy, Stem Cell Reports, Volume 16, Issue 3, Pages 666-668. https://doi.org/10.1016/j.stemcr.2021.01.012.",

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Ghazizadeh, Z, Fattahi, F, Mirzaei, M, Bayersaikhan, D, Lee, J, Chae, S, Hwang, D, Byun, K, Tabar, MS, Taleahmad, S, Mirshahvaladi, S, Shabani, P, Fonoudi, H, Haynes, PA, Baharvand, H, Aghdami, N, Evans, T, Lee, B & Salekdeh, GH 2018, 'Prospective isolation of ISL1⁺ cardiac progenitors from human ESCs for myocardial infarction therapy', Stem Cell Reports, vol. 10, no. 3, pp. 848-859. https://doi.org/10.1016/j.stemcr.2018.01.037

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AU - Ghazizadeh, Zaniar

AU - Fattahi, Faranak

AU - Mirzaei, Mehdi

AU - Bayersaikhan, Delger

AU - Lee, Jaesuk

AU - Chae, Sehyun

AU - Hwang, Daehee

AU - Byun, Kyunghee

AU - Tabar, Mehdi Sharifi

AU - Taleahmad, Sara

AU - Mirshahvaladi, Shahab

AU - Shabani, Parisa

AU - Fonoudi, Hananeh

AU - Haynes, Paul A.

AU - Baharvand, Hossein

AU - Aghdami, Nasser

AU - Evans, Todd

AU - Lee, Bonghee

AU - Salekdeh, Ghasem Hosseini

N1 - 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. Correction: 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 (2021) Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy, Stem Cell Reports, Volume 16, Issue 3, Pages 666-668. https://doi.org/10.1016/j.stemcr.2021.01.012.

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N2 - 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.

AB - 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.

KW - cell therapy

KW - myocardial biology

KW - proteomics

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