Abstract 16862: Culture of Cardiac Mesenchymal Cells (CMCs) at Physiologic Oxygen Tension Greatly Enhances Cell Retention In Vivo After Myocardial Infarction

Abstract

A major obstacle to using cell therapy for heart failure is the poor survival of transplanted cells. We have found that CMCs (a promising type of reparative cells) grown at 5% O 2 (the physiologic O 2 tension in the heart) are more resistant to severe hypoxia in vitro than CMCs grown at 21% O 2 , but the survival of these cells in vivo is unknown. Thus, female mice subjected to a 60-min coronary occlusion and 30 days of reperfusion received 1x10 6 male CMCs cultured at 21% O 2 or 5% O 2 (21%O 2 CMCs or 5%O 2 CMCs) via echo-guided injection into the LV cavity. Quantitative real-time PCR for single copy of a Y-chromosome-specific Sry gene sequence was performed using genomic DNA isolated from heart (right ventricle [RV], risk region [RR] and non-risk region [NR] of LV), lung, liver, spleen and kidney 24 h or 7 days after cell administration (Figure). Compared with 21% O 2 CMCs, culture at 5% O 2 markedly increased cell retention in RR > NR > RV at 24 h and up to 7 days after CMC administration (Figs. C-D). At 24 h, although 25% of all transplanted cells were present in the liver (Fig. E), the number of Sry + cells per mg of tissue was strikingly greater in RR (2131±248) > NR (1447±250) > RV (1047±156) compared with liver (274±131, P <0.01) and kidney (619±140, P <0.05) (n=6/group). These differences persisted up to 7 days (820±156 in RR, 667±156 in NR, 327±33 in RV vs. 103±45 in liver, P <0.01; 179±50 in kidney, P <0.05) (n=4-5/group). In summary, we provide a systematic, time-dependent, and highly quantitative analysis of cell retention and distribution after infusion of CMCs into the LV cavity of failing hearts. The results demonstrate that, compared with 21% O 2 , physiologic 5% O 2 tension greatly enhances the retention of CMCs in the heart at 24 h and 7 days after cell transplantation, especially in the scarred regions where O 2 is very low (1-2%). Thus, culture at 5% O 2 may improve the reparative properties of CMCs (and possibly other cell types) used for cell therapy, providing an approach that may be applicable in the clinic.