Human myocardial-derived highly proliferative cells improve cardiac remodeling after myocardial infarction in mice.

Document Type

Article

Publication Date

9-2025

Institution/Department

Center for Molecular Medicine

Journal Title

The Journal of pharmacology and experimental therapeutics

MeSH Headings

Animals, Myocardial Infarction, Humans, Mice, Male, Female, Cell Proliferation, Ventricular Remodeling, Myocardium, Mice, Inbred C57BL

Abstract

Human highly proliferative cells (hHiPCs) isolated from the adult heart have progenitor and angiogenic properties. However, the mechanisms underlying hHiPCs in myocardial repair in vivo have yet to be investigated. We characterized the hHiPC proteome and secretome and found that hHiPCs express and secrete proangiogenic and proreparative proteins, including CXCL6, CTHRC1, and CD73, and are ontologically enriched in pathways related to cytokine signaling and glucose metabolism. Using publicly available single-cell data (GSE149699), we found that CXCL6, CTHRC1, and CD73 are also expressed in adult and neonatal cardiospheres, resembling a therapeutic cell population currently being tested in clinical trials. With the prominent role of these enriched secreted factors in cardiac repair and highly proliferative phenotype, we hypothesized that hHiPC injection would improve heart function following ischemic injury. Following experimental myocardial infarction (MI) in immunocompromised male and female mice, we found that intramyocardial injection of hHiPCs (2.5 × 10

ISSN

1521-0103

First Page

103673

Last Page

103673

Link to Full Text

Share

COinS