Cardiac regenerative potential of cardiosphere‐derived cells from adult dog hearts

Abstract

The regenerative potential of cardiosphere-derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin-induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM.

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

“…Derivation and culture of cCDCs Canine CDCs were generated and expanded as described [3,12] from myocardial specimens of a healthy male beagle dog [8,13]. Briefly, this tissue was surgically collected from the right ventricle of a 2-year-old canine beagle.…”

Notch pathway activation enhances cardiosphere in vitro expansion

“…Cardiospheres (CSps) are cardiac‐derived multicellular clusters, considered a reliable in vitro model of the cardiac microenvironment, hosting a reservoir of both immature and committed progenitors towards the three major cardiac cell lineages: cardiomyocytes, endothelial cells (ECs) and smooth muscle cells (SMCs) . CSps transplantation into infarcted hearts results in enhanced in vivo cell survival and cardioprotection . Recent data have shown that activation of the Notch signalling pathway promotes cell differentiation along the vascular smooth muscle lineage in CSp‐derived cells and is sensitive to oxygen tension in the tridimensional cellular array …”

“…21 CSps transplantation into infarcted hearts results in enhanced in vivo cell survival and cardioprotection. 22 Recent data have shown that activation of the Notch signalling pathway promotes cell differentiation along the vascular smooth muscle lineage in CSp-derived cells and is sensitive to oxygen tension in the tridimensional cellular array. 23 In this work, we aimed at dissecting the specific role of Notch1 signalling in CSps.…”

New Strategies for Myocardial Infarction Treatment

“…In animal experiments, cardiac stem cells were injected into the heart of mice with heart disease, and the injected cells directly migrated to the damaged heart tissue, promoted the regeneration of myocardium, and improved the ability of the heart to pump blood [44] . Multiple types of CSCs have been identified including Islet-1+ cells, Sca-1+ cells, cardiosphere derived cells (CDCs), cardiac mesoangioblasts, cardiac specific side population, and epicardial progenitors [45][46][47][48][49][50] . A lot of preclinical researches in both small and large animal models have indicated the potential of CSCs therapy in treating MI (Table1).…”