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Updated: May 12, 2026
Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Human myocardial-derived highly proliferative cells improve cardiac remodeling after myocardial infarction in mice
Michayla Moore1, Elena Chepurko2, Vadim Chepurko2
1Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, Scarborough, Maine; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, Maine.
Insights
Human highly proliferative cells (hHiPCs) from the heart show potential for myocardial repair. These cells secrete proangiogenic factors and improve heart function after injury, suggesting a new cell therapy for ischemic heart disease.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Cell Therapy
Background:
- Human highly proliferative cells (hHiPCs) from adult hearts possess progenitor and angiogenic properties.
- Mechanisms of hHiPC-mediated myocardial repair in vivo remain largely uninvestigated.
- Existing clinical trials are testing cardiosphere-derived cells, which share molecular markers with hHiPCs.
Purpose of the Study:
- To characterize the proteome and secretome of hHiPCs.
- To investigate the therapeutic potential of hHiPCs in a mouse model of myocardial infarction (MI).
- To determine if hHiPC injection improves cardiac function and prevents adverse remodeling post-MI.
Main Methods:
- Proteomic and secretomic analysis of hHiPCs.
- In vivo transplantation of hHiPCs into immunocompromised mice post-MI.
- Assessment of cell survival, cardiac function (fractional shortening), and ventricular remodeling.
Main Results:
- hHiPCs express and secrete proangiogenic/proreparative proteins (CXCL6, CTHRC1, CD73).
- Intramyocardial injection of hHiPCs led to cell survival in the host myocardium during the acute phase post-MI.
- hHiPC treatment improved fractional shortening and prevented ventricular remodeling at 21 and 28 days post-MI.
Conclusions:
- hHiPCs exhibit properties conducive to cardiac repair.
- hHiPCs survive and exert beneficial effects in the ischemic myocardium.
- hHiPCs represent a promising cell-based therapeutic strategy for myocardial ischemic injury.
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 × 105 cells) resulted in ∼3.5% (∼8.7 × 103 cells) survival in the host myocardium; however, hHiPC survival persisted throughout the acute phase of MI. To assess cardiac function after treatment, we found that hHiPCs improved fractional shortening by 21 and 28 days post-MI and prevented progressive ventricular remodeling compared with vehicle control treatment. Together, these data establish a role for hHiPCs in cardiac repair and lay the foundation for their investigation as a potential treatment for myocardial ischemic injury. SIGNIFICANCE STATEMENT: This study determined the unique novel properties of cardiac-derived human highly proliferative cells (hHiPCs) to survive over the acute inflammatory phase in the ischemic myocardium. hHIPCs were identified as potential candidates for cell-based therapy to create a long-term prohealing microenvironment by secreting proreparative proteins CXCL6, CTHRC1, and CD73.
