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Updated: Dec 8, 2025
Ultrasound-Guided Induced Pluripotent Stem Cell-Derived Cardiomyocyte Implantation in Myocardial Infarcted Mice
Published on: March 30, 2022
Transplanted microvessels improve pluripotent stem cell-derived cardiomyocyte engraftment and cardiac function after
Xuetao Sun1, Jun Wu2, Beiping Qiang3
1Toronto General Hospital Research Institute, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada.
Insights
Transplanting microvessels with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) significantly improves cell survival and heart function after myocardial infarction in rats. This approach enhances regenerative therapies for heart repair.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show promise for repairing infarcted hearts.
- Limited hiPSC-CM survival in the ischemic environment hinders their clinical application.
Purpose of the Study:
- To enhance hiPSC-CM survival and functional recovery post-transplantation in infarcted hearts.
- To evaluate the efficacy of cotransplanting ready-made microvessels with hiPSC-CMs.
Main Methods:
- Established a method for cotransplanting hiPSC-CMs with ready-made microvessels from adipose tissue into infarcted rat hearts.
- Compared outcomes with hiPSC-CMs transplanted alone or with dissociated endothelial cells.
Main Results:
- Ready-made microvessels increased hiPSC-CM survival sixfold and improved functional recovery.
- Microvessels demonstrated high persistence and integration, enhancing graft perfusion and hiPSC-CM maturation.
- Significant improvements in vessel density and graft perfusion were observed.
Conclusions:
- Cotransplantation of ready-made microvessels is a viable strategy to improve hiPSC-CM survival and function.
- This approach offers a promising cell-based therapy for myocardial infarction, enhancing regenerative potential.
Abstract:
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer an unprecedented opportunity to remuscularize infarcted human hearts. However, studies have shown that most hiPSC-CMs do not survive after transplantation into the ischemic myocardial environment, limiting their regenerative potential and clinical application. We established a method to improve hiPSC-CM survival by cotransplanting ready-made microvessels obtained from adipose tissue. Ready-made microvessels promoted a sixfold increase in hiPSC-CM survival and superior functional recovery when compared to hiPSC-CMs transplanted alone or cotransplanted with a suspension of dissociated endothelial cells in infarcted rat hearts. Microvessels showed unprecedented persistence and integration at both early (~80%, week 1) and late (~60%, week 4) time points, resulting in increased vessel density and graft perfusion, and improved hiPSC-CM maturation. These findings provide an approach to cell-based therapies for myocardial infarction, whereby incorporation of ready-made microvessels can improve functional outcomes in cell replacement therapies.
