Abstract 250: Pericardial Grafting Of Cardiac Progenitor Cells In The Three-dimensional Thick Scaffold Improves Cardiac Function After Myocardial Infarction In Mice.
Cardiac progenitor cell (CPC) therapy for heart disease has been examined enthusiastically. However, optimal scaffolds which maintain the transplanted cells are still elusive. We used clonally expanded stem cell antigen 1-positive CPCs from adult mice and produced a three-dimensional thick scaffold (CPC-scaffold), in which CPCs were cultivated up to 2 month with self-assembling peptide RADA16-I. Addition of designer self-assembling peptide containing the active motifs of 2-unit RGD binding sequence and IGF-1 promoted three-dimensional spreading and viability of CPCs. After making myocardial infarction (MI) with left coronary artery ligation in mice, we transplanted CPC-scaffold on the surface of infarction area and confined it inside of the pericardial space by closing parietal pericardium. Four weeks after transplantation, echocardiography showed that FS of treatment group (16±10%, n=17) was higher than that of control (MI only) group (10±6.8%, n=19) (P<0.05) and that LVDd of treatment group (5.4±1.0mm, n=17) was smaller than that of control group (6.2±1.1mm, n=19) (P<0.05). Infarction area was significantly decreased in treatment group (46±21%, n=17), compared to control group (59±19%, n=18) (P<0.05). Immunohistochemical staining for von-Willebrand factor (vWF) showed that the number of vWF-positive capillaries per mm2 in treatment group (16.8±3.2, n=5) was higher than that of control group(8.9±3.4, n=5) (P<0.05). There were many of CD31-positive capillaries with or without α-smooth muscle cell actin-expressing perivascular cells in the graft area. By using fluorescent-conjugated avidin, biotin-labeled scaffold was globally detected in the graft area 1 week after transplantation, but sparsely 4weeks after, suggesting that the transplanted scaffold was biodegradable. To examine whether transplanted CPCs remain in the scaffold, we labeled CPCs with red fluorescence protein (RFP). RFP+CPCs were observed in the graft area 4 weeks after transplantation of RFP+CPC-scaffold. FISH analysis showed that sex-mismatched CPCs were globally detected in the graft area on the surface of the heart. Therefore pericardial grafting of well-vascularized and cellularized CPC-scaffold was a useful method to improve cardiac function after MI.
Author Disclosures: N. Kondo: None T. Nagai: None M. Liu: None T. Takahashi: None M. Kanda: None K. Matsuura: None I. Komuro: None Y. Kobayashi: None.
- © 2014 by American Heart Association, Inc.