1 Department of Urology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
2 Department of Central Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Cell Transplant. 2019 Mar;28(3):328-342. doi: 10.1177/0963689718821682. Epub 2019 Jan 9.
The survival of engineered tissue requires the formation of its own capillary network, which can anastomose with the host vasculature after transplantation. Currently, while many strategies, such as modifying the scaffold material, adding endothelial cells, or angiogenic factors, have been researched, engineered tissue implanted in vivo cannot timely access to sufficient blood supply, leading to ischemic apoptosis or shrinkage. Constructing vascularized engineered tissue with its own axial vessels and subsequent pedicled transfer is promising to solve the problem of vascularization in tissue engineering. In this study, we used the tissue expander capsule as a novel platform for vascularizing autologous smooth muscle cell (SMC) sheets and fabricating vascularized engineered tissue with its own vascular pedicle. First, we verified which time point was the most effective for constructing an axial capsule vascular bed. Second, we compared the outcome of SMC sheet transplantation onto the expander capsule and classical dorsal subcutaneous tissue, which was widely used in other studies for vascularization. Finally, we transplanted multilayered SMC sheets onto the capsule bed twice to verify the feasibility of fabricating thick pedicled engineered smooth muscle tissues. The results indicated that the axial capsule tissue could be successfully induced, and the capsule tissue 1 week after full expansion was the most vascularized. Quantitative comparisons of thickness, vessel density, and apoptosis of cell sheet grafts onto two vascular beds proved that the axial capsule vascular bed was more favorable to the growth and vascularization of transplants than classical subcutaneous tissue. Furthermore, thick vascularized smooth muscle tissues with the vascular pedicle could be constructed by multi-transplanting cell sheets onto the capsule bed. The combination of axial capsule vascular bed and cell sheet engineering may provide an efficient strategy to overcome the problem of slow or insufficient vascularization in tissue engineering.
工程化组织的存活需要形成自身的毛细血管网络，该网络在移植后可与宿主脉管系统吻合。目前，虽然已经研究了许多策略，例如修饰支架材料、添加内皮细胞或血管生成因子等，但植入体内的工程化组织不能及时获得足够的血液供应，导致缺血性细胞凋亡或萎缩。构建具有自身轴向血管的血管化工程化组织，并随后进行带蒂转移，有望解决组织工程中的血管化问题。在本研究中，我们使用组织扩张器胶囊作为一种新颖的平台，用于血管化自体平滑肌细胞（SMC）片，并构建具有自身血管蒂的血管化工程化组织。首先，我们验证了构建轴向胶囊血管床的最有效时间点。其次，我们比较了SMC 片在扩张器胶囊和经典背侧皮下组织上的移植结果，经典背侧皮下组织在其他研究中广泛用于血管化。最后，我们将多层 SMC 片两次移植到胶囊床上，以验证构建厚蒂工程化平滑肌组织的可行性。结果表明，轴向胶囊组织可以成功诱导，并且完全扩张后 1 周的胶囊组织血管化程度最高。对两种血管床移植片的厚度、血管密度和细胞凋亡的定量比较证明，轴向胶囊血管床比经典皮下组织更有利于移植物的生长和血管化。此外，通过将细胞片多次移植到胶囊床上，可以构建具有蒂的厚血管化平滑肌组织。轴向胶囊血管床和细胞片工程的结合可能为克服组织工程中血管化缓慢或不足的问题提供一种有效的策略。
