Description
Background – Prospective immunoselection has been advocated as a strategy to enrich the purity of mesenchymal precursor cells (MPC) from bone marrow (BM). MPC have shown trophic capacity to mediate cardiovascular repair in myocardial ischaemia. However, their efficacy in nonischaemic cardiomyopathy (NICM) remains undetermined. We studied the biological properties and cardiovascular paracrine effects of MPC in vitro and evaluated intramyocardial, allogeneic MPC therapy in experimental NICM. Methods and Results – Human and ovine MPC were prepared by immunoselection of BM mononuclear cells, using a monoclonal antibody to STRO-3 (tissue nonspecific alkaline phosphatase). Human STRO-3+ MPC were compared for their biological characteristics to conventionally prepared, plastic adherence-isolated mesenchymal stromal cells (MSC), prepared from the same BM donors. STRO-3+ MPC demonstrated more immature, “stem-cell” like properties in vitro, including enhanced clonogenicity, purity, proliferation and multi-lineage differentiation potential. Compared to control media, MPC conditioned media contained cardiovascular relevant cytokines (SDF-1α, VEGF, MCP-1, IL-6, HGF) and augmented endothelial tube formation, cardiomyocyte proliferation and migration, and attenuated cardiomyocyte apoptosis after exposure to hypoxia and doxorubicin. Sixteen sheep with doxorubicin-induced NICM were then randomised to allogeneic STRO-3+ MPC or placebo, delivered by catheter-based, intramyocardial injections under NOGA® XP guidance. Left ventricular ejection fraction remained stable eight weeks after MPC transplantation, but continued to decline after placebo (P<0.05). Although MPC therapy did not prevent LV dilatation, it was associated with lower myocardial fibrosis (P<0.05), increased cardiomyocyte proliferation and increased neovascularisation.| Period | 2009 |
|---|---|
| Event title | Young Investigator Award Finals - WinnerAustralian Society of Medical Research |
| Event type | Conference |
| Location | AustraliaShow on map |