Collagen–GAG Scaffolds Grafted onto Myocardial Infarcts in a Rat Model: A Delivery Vehicle for Mesenchymal Stem Cells

Abstract

Various cell delivery methods have been investigated for cell transplantation treatment of cardiac infarcts. In this study, we investigated a type I collagen–glycosaminoglycan (GAG) scaffold for the implantation of adult bone marrow–derived mesenchymal stem cells (MSCs) into the infarcted region in the rat heart. The objective was to evaluate the tissue response to collagen–GAG scaffolds prepared using 2 cross-linking methods. The left coronary artery of female Wistar rats was occluded for 60 min, followed by reperfusion. One week later, the infarcted region was implanted with (1) collagen–GAG scaffolds cross-linked by dehydrothermal treatment alone (DHT; n = 10); (2) collagen–GAG scaffolds cross-linked by DHT followed by carbodiimide treatment (EDAC; n = 8); or (3) DHT cross-linked collagen–GAG scaffolds seeded with bromodeoxyuridine (BrdU)-labeled allogeneic MSCs (cell-scaffold; n = 9). Shamoperated rats served as controls (n = 4). Specimens were harvested 3 weeks after the implantation surgery. The tissue response was evaluated histomorphometrically and by immunohistochemistry to track the BrdU-labeled MSCs. Most of the DHT cross-linked collagen–GAG scaffolds degraded, whereas the scaffolds in the EDAC group appeared to be largely intact. There were no signs of acute inflammation in any of the groups. A substantial amount of neovascularization was seen in the infarcted region in the implant groups and in the scaffolds themselves. BrdU-positive cells appeared both in the degraded scaffold and the infarct region. DHT cross-linked collagen–GAG scaffolds warrant continued investigation as delivery vehicles for implantation of cells into infarcted cardiac tissue.