Abstract 16918: Autologous Tissue Engineering Scaffolds for Cellular Cardiomyoplasty

Abstract

BACKGROUND: Cellular cardiomyoplasty for treatment of cardiomyopathy is limited by low levels of acute retention (∼20%) of transplanted stem cells in the myocardium which results in low long term engraftment (<5%), causing marginal functional benefit. OBJECTIVES: To design a biocompatible and biodegradable autologous hydrogel scaffold for improving acute retention, preventing anoikis/apoptosis, and increasing engraftment. METHODS: Hydrogel scaffolds were prepared by cross-linking modified hyaluronic acid (HA) with polyethylene glycol (PEG), autologous blood (Bl) or serum (Ser). Cardiosphere-derived cells (CDCs) were isolated from syngeneic, male Wistar Kyoto rats. Cell viability and integrin activation in scaffolds were examined by 2-photon microscopy. Glucose ( 18 FDG) uptake of CDC in scaffolds was measured to assess cellular metabolic status, and compared with 18 FDG uptake of suspended and adherent cells. Acute retention rate in the myocardium was determined by ex-vivo counting with a gamma-counter and PET/CT imaging after intra-myocardial injection of 1x10 6 18 FDG labeled CDC. RESULTS: Hydrogel scaffolds with similar mechanical strength as myocardium (2-4 kPa) were found to be optimal for animal survival. CDC viability in the autologous scaffolds was superior to HA-PEG in the absence of external nutrients with >80 ± 10% vs. 0% viability when cultured in Tyrode for 10 days. 18 FDG uptake of cells encapsulated within various scaffolds was similar to adherent cells, but found to be 9 fold for HA-Bl, 11 fold for HA-Bl:Ser, and 15 fold for HA-Ser ( p < 0.05) compared with suspended cells. Integrin activation in the cells was observed within 95 ± 2.6% in scaffolds compared to 15.7 ± 8.2% in PBS. CONCLUSIONS: Autologous biodegradable tissue engineering scaffolds composed of HA and blood components greatly increased acute CDC retention in the myocardium after intramyocardial delivery. These scaffolds also served as a temporary matrix for cellular attachment and a source of nutrients/growth factors for stem cells survival.