Sun Peng, Wu Haoliang, Bai Xiche, Zhang Liwei, Zhang Cong, Wang Xueyun, Lou Chunyang, Li Bo, Li Zhuo, Bai Hualong
Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, Zhengzhou, China.
J Biomed Mater Res B Appl Biomater. 2023 Mar;111(3):551-559. doi: 10.1002/jbm.b.35172. Epub 2022 Oct 6.
We previously showed decellularized fish swim bladder can be used as vascular patch and tube graft in rats, mesenchymal stem cells (MSCs) have showed the capability to inhibit neointimal hyperplasia in different animal models. We hypothesized that decellularized fish swim bladder patch loaded with MSCs (bioinspired patch) can inhibit neointimal hyperplasia in a rat aortic patch angioplasty model. Rat MSCs were grown in vitro and flow cytometry was used to confirm their quality. 3.6 × 10 MSCs were mixed into 100 μl of sodium alginate (SA)/hyaluronic acid (HA) hydrogel, two layers of fish swim bladders (5 mm × 5 mm) were sutured together, bioinspired patch was created by injection of hydrogel with MSCs into the space between two layers of fish swim bladder patches. Decellularized rat thoracic aorta patch was used as control. Patches were harvested at days 1 and 14 after implantation. Samples were examined by histology, immunohistochemistry, and immunofluorescence. The decellularized rat thoracic aorta patch and the fish swim bladder patch had a similar healing process after implantation. The bioinspired patch had a similar structure like native aorta. Bioinspired patch showed a decreased neointimal thickness (p = .0053), fewer macrophages infiltration (p = .0090), and lower proliferation rate (p = .0291) compared to the double layers fish swim bladder patch group. Decellularized fish swim bladder patch loaded with MSCs can inhibit neointimal hyperplasia effectively. Although this is a preliminary animal study, it may have a potential application in large animals or clinical research.
我们之前表明，去细胞化的鱼鳔可作为大鼠的血管补片和管状移植物，间充质干细胞（MSCs）已显示出在不同动物模型中抑制内膜增生的能力。我们假设，负载MSCs的去细胞化鱼鳔补片（生物启发补片）可在大鼠主动脉补片血管成形术模型中抑制内膜增生。大鼠MSCs在体外培养，并用流式细胞术确认其质量。将3.6×10个MSCs混入100μl海藻酸钠（SA）/透明质酸（HA）水凝胶中，将两层鱼鳔（5mm×5mm）缝合在一起，通过将含有MSCs的水凝胶注入两层鱼鳔补片之间的空间来制备生物启发补片。使用去细胞化的大鼠胸主动脉补片作为对照。在植入后第1天和第14天收获补片。通过组织学、免疫组织化学和免疫荧光检查样本。去细胞化的大鼠胸主动脉补片和鱼鳔补片在植入后具有相似的愈合过程。生物启发补片具有与天然主动脉相似的结构。与双层鱼鳔补片组相比，生物启发补片显示内膜厚度降低（p = .0053）、巨噬细胞浸润减少（p = .0090）和增殖率降低（p = .0291）。负载MSCs的去细胞化鱼鳔补片可有效抑制内膜增生。尽管这是一项初步的动物研究，但它可能在大型动物或临床研究中有潜在应用。
