Ozawa Tsukasa, Mickle Donald A G, Weisel Richard D, Matsubayashi Keiji, Fujii Takeshiro, Fedak Paul W M, Koyama Nobuya, Ikada Yoshito, Li Ren-Ke
Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Canada.
Toho University School of Medicine, Japan.
Cell Transplant. 2004 Mar;13(2):169-177. doi: 10.3727/000000004773301852.
Autologous smooth muscle cell (SMC)-seeded biodegradable scaffolds could be a suitable material to repair some pediatric right ventricular outflow tract (RVOT) cardiac anomalies. Adult syngenic Lewis rat SMCs (2 × 106) were seeded onto a new biodegradable copolymer sponge made of ∊-caprolactone-co-L-lactide reinforced with poly-L-lactide fabric (PCLA). Two weeks after seeding, the patch was used to repair a surgically created RVOT defect in an adult rat. At 8 weeks after implantation the spongy copolymer component was biodegraded, and SM tissue and extracellular matrices containing elastin fibers were present in the scaffolds. By 22 weeks more fibroblasts and collagen were present (p < 0.05). The number of capillaries in the grafts also increased (p < 0.001) between 8 and 22 weeks. The fibrous poly-L-lactide component of the PCLA scaffold remained. The 22-week grafts maintained their thickness and surface area in the RVOT. The SMCs prior to implantation were in a synthetic phenotype and developed in vivo into a more contractile phenotype. By 8 weeks the patches were endothelialized on their endocardial surfaces. Future work to increase the SM tissue and elastin content in the patch will be necessary before implantation into a pediatric large-animal model is tested.
接种自体平滑肌细胞(SMC)的可生物降解支架可能是修复某些小儿右心室流出道(RVOT)心脏异常的合适材料。将成年同基因Lewis大鼠的平滑肌细胞(2×10⁶个)接种到一种新型的可生物降解共聚物海绵上,该海绵由聚-L-丙交酯织物增强的ε-己内酯-co-L-丙交酯制成(PCLA)。接种两周后,将补片用于修复成年大鼠手术造成的RVOT缺损。植入8周后,海绵状共聚物成分发生生物降解,支架中出现含有弹性纤维的平滑肌组织和细胞外基质。到22周时,出现了更多的成纤维细胞和胶原蛋白(p<0.05)。在8至22周之间,移植物中的毛细血管数量也增加了(p<0.001)。PCLA支架的纤维状聚-L-丙交酯成分保留了下来。22周的移植物在RVOT中保持了其厚度和表面积。植入前的平滑肌细胞呈合成表型,并在体内发展为更具收缩性的表型。到8周时,补片的心内膜表面已内皮化。在测试植入小儿大型动物模型之前,未来有必要开展工作增加补片中的平滑肌组织和弹性蛋白含量。