Abstract 345: Tissue-Printed Cardiac Progenitor Cells Improve Myocardial Function in a Mouse Model of MI

Abstract

Introduction: Tissue engineering is emerging as a therapeutic approach to overcome the limitations of cell therapy and mechanically support the ventricular wall. Tissue printing technology (TP) allows for the construction of a defined and organized tissue engineered construct. Hypothesis: The aim of our study was to evaluate the combination of TP and cardiac-derived cardiomyocyte progenitor cells (CMPCs) to build a cardiogenic construct. Methods: Sca-1 + CMPCs were printed in gelatin/hyaluronic acid matrix (30x10 6 cells/ ml) to form a biocomplex made of 6 perpendicularly printed layers with a surface of 2cm x 2cm and a structure 500 µm thick. After in vitro characterization, the printed biocomplex was transplanted in a mouse model of MI. Cardiac function was evaluated by MRI. Results: After printing, CMPCs retain cardiogenic gene expression for up to 4 weeks, as evaluated by PCR (n=4). Immunofluorescence analysis confirmed expression of Nkx2.5 and Ki67 with a slight decrease after 7 days in culture (77% vs 52% and 79% vs 64% respectively, n=5, p<0.05). After differentiation, hCMPCs increased MLC2a and TnI gene levels (n=4). In vivo engrafted hCMPCs expressed Nkx 2.5. TnI expression was also detected after 2 weeks (n=3) and 28 days (n=5). CD31 expression was detected in low number of transplanted hCMPCs. Endogenous CD45 expression was similar at 7 and 14 days, mainly localized at the border of the matrix (n=3). At 28 days, a reduction in EDV and ESV dilation was observed, as compared to control (EDV:107,87 ± 7,41 vs 136,6 ±9,6 and ESV:89 ± 6,6 vs 118 ±12, respectively, n=8 each group, p<0.05), although no significant differences could be observed with matrix only (EDV;107,87 ± 7,41 vs 120,8 ±9,5 and ESV;89 ± 6,6 vs 97 ±10, respectively, n=7). Infarct wall thinning was reduced in both groups compare to the control (457 ± 69,8 vs 357,8 ±18,6 and 201,1± 6,3 μ m, respectively; n=5 each group, p<0.05). Conclusion: Here, we showed that hCMPCs can be printed and cultured in Gel/ HA. Transplantation in a mouse model of MI contributed to an improvement in cardiac function and a better remodeling upon injury. Long-term follow up to address its effect on infarct size, cardiomyocytes survival and regeneration, revascularization, endogenous CPCs activation, and inflammation is ongoing.