title: ISL1 cardiovascular progenitor cells for cardiac repair after myocardial infarction.
abstract: Cardiovascular progenitor cells (CPCs) expressing the ISL1-LIM-homeodomain transcription factor contribute developmentally to cardiomyocytes in all 4 chambers of the heart. Here, we show that ISL1-CPCs can be applied to myocardial regeneration following injury. We used a rapid 3D methylcellulose approach to form murine and human ISL1-CPC spheroids that engrafted after myocardial infarction in murine hearts, where they differentiated into cardiomyocytes and endothelial cells, integrating into the myocardium and forming new blood vessels. ISL1-CPC spheroid-treated mice exhibited reduced infarct area and increased blood vessel formation compared with control animals. Moreover, left ventricular (LV) contractile function was significantly better in mice transplanted with ISL1-CPCs 4 weeks after injury than that in control animals. These results provide proof-of-concept of a cardiac repair strategy employing ISL1-CPCs that, based on our previous lineage-tracing studies, are committed to forming heart tissue, in combination with a robust methylcellulose spheroid-based delivery approach.
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.|Yale Stem Cell Center.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bartulos
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.
authors.forename: Zhen Wu
authors.initials: ZW
authors.lastname: Zhuang
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mikush
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.|Yale Stem Cell Center.
authors.forename: Carol
authors.initials: C
authors.lastname: Suh
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.
authors.forename: Alda
authors.initials: A
authors.lastname: Bregasi
authors.affiliation: Yale Stem Cell Center.|Department of Laboratory Medicine.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Section of Nephrology.
authors.forename: William
authors.initials: W
authors.lastname: Chang
authors.affiliation: Yale Stem Cell Center.|Department of Laboratory Medicine.|Department of Cell Biology.|Pathology.
authors.forename: Diane S
authors.initials: DS
authors.lastname: Krause
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.|Cellular and Molecular Physiology.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Young
authors.affiliation: Pathology.|Immunobiology, and.|Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut, USA.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine.|Yale Stem Cell Center.|Pathology.|Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut, USA.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Qyang