Xiang Zhou, Liao Ronglih, Kelly Matthew S, Spector Myron
Department of Orthopaedic Surgery, Huaxi Hospital, Sichuan University, Chengdu, China.
Tissue Eng. 2006 Sep;12(9):2467-78. doi: 10.1089/ten.2006.12.2467.
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.
为了进行心脏梗死的细胞移植治疗，人们研究了多种细胞递送方法。在本研究中，我们研究了一种I型胶原-糖胺聚糖（GAG）支架，用于将成年骨髓来源的间充质干细胞（MSCs）植入大鼠心脏的梗死区域。目的是评估对使用两种交联方法制备的胶原-GAG支架的组织反应。雌性Wistar大鼠的左冠状动脉闭塞60分钟，然后再灌注。一周后，梗死区域植入（1）仅通过脱氢热处理交联的胶原-GAG支架（DHT；n = 10）；（2）通过DHT交联后再进行碳二亚胺处理的胶原-GAG支架（EDAC；n = 8）；或（3）接种了溴脱氧尿苷（BrdU）标记的同种异体MSCs的DHT交联胶原-GAG支架（细胞-支架；n = 9）。假手术大鼠作为对照（n = 4）。在植入手术后3周收获标本。通过组织形态计量学和免疫组织化学评估组织反应，以追踪BrdU标记的MSCs。大多数DHT交联的胶原-GAG支架降解，而EDAC组的支架似乎基本完好。任何一组均未出现急性炎症迹象。在植入组的梗死区域和支架本身中均可见大量新生血管形成。BrdU阳性细胞出现在降解的支架和梗死区域中。DHT交联的胶原-GAG支架作为将细胞植入梗死心脏组织的递送载体值得继续研究。
