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Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy
Michael Taylor Hensley1, Junnan Tang1,2, Kathleen Woodruff3
1Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
Insights
Allogeneic cardiosphere-derived cells (CDCs) show promise for treating dilated cardiomyopathy (DCM). This study found canine CDCs (cCDCs) to be safe and well-tolerated in a large animal model, with no adverse events or immune rejection observed.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Cell Therapy
Background:
- Cardiosphere-derived cells (CDCs) have demonstrated efficacy in reducing myocardial scar size and increasing viable heart muscle in human myocardial infarction patients.
- Preclinical rodent studies suggest potential therapeutic benefits of CDC therapy for non-ischaemic dilated cardiomyopathy (DCM).
Purpose of the Study:
- To evaluate the safety and efficacy of allogeneic CDCs in a large animal model of spontaneous DCM.
- To assess potential adverse events and immune responses following allogeneic CDC transplantation in dogs with DCM.
Main Methods:
- Canine CDCs (cCDCs) were cultured from donor dog hearts, characterized by cell surface markers (CD105, c-kit, CD90).
- Thirty million allogeneic cCDCs were infused into the coronary vessels of Doberman pinschers diagnosed with spontaneous DCM.
- Safety was monitored through adverse event tracking, and cardiac function was assessed via echocardiography.
Main Results:
- No adverse events were observed during or after the infusion of cCDCs.
- Post-mortem histological examination of transplanted hearts showed no signs of immune rejection.
- Cardiac function measurements indicated the safety profile of the intervention.
Conclusions:
- Allogeneic cCDC therapy is safe and well-tolerated in a canine model of spontaneous DCM.
- The absence of adverse events and immune rejection supports further investigation of CDC therapy for DCM.
- This large animal model provides a valuable platform for advancing CDC-based regenerative strategies for heart failure.
Abstract:
Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells.

