Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy.

Michael Taylor Hensley,Bruce Keene,Kathryn Meurs,Sandra Tou,Kathleen Woodruff,Mathew Breen,Teresa Defrancesco,Ke Cheng,Junnan Tang,Christina M Williams

doi:10.1111/jcmm.13077

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.

Highlights

Heart diseases remain the number one killer in western countries [1]
Results from a recent clinical trial indicated that infusion of autologous Cardiosphere-derived cells (CDCs) in patients with mild-to-moderate myocardial infarction reduced scar but increased viable tissue [8]
A phase II clinical trial is ongoing to test the regenerative potential of allogeneic CDCs in patients with recent myocardial infarction (MI) [21]

Summary

Introduction

Heart diseases remain the number one killer in western countries [1]. Stem cell transplantation is a promising therapeutic strategy for acute or chronic cardiomyopathy, considering current treatments for human DCM usually involve intense drug regimen and/or invasive implantable devices [2]. Small animal (rodent) studies are widely adopted for initial proof of concept [3]. Translation to human trials necessitates large animal studies (e.g. pigs, dogs). One dilemma is that many naturally occurring cardiomyopathies in humans cannot be modelled effectively in the laboratory. Naturally occurring cardiomyopathy affects the well-being of domestic dogs. In Doberman pinschers, the DCM appears to represent a major cause of death [4].

Methods

Results

Conclusion