Peter Viktor Hauser, Lifu Zhao, Hsiao-Min Chang, Norimoto Yanagawa, Morgan Hamon
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Loading the chamber with collagen I (C), Matrigel (M), or Matrigel + vascular endothelial growth factor) (MV) had a strong influence on vascularization speed: Chambers loaded with C took 7 days to vascularize, 4 days for chambers with M, and 2 days for chambers with MV. Implantation of E12.5 mouse embryonic kidneys into prevascularized chambers (C, MV) was followed with significant growth and ureteric branching over 22 days. In contrast, the growth of kidneys in non-prevascularized chambers was stunted. We concluded that our prevascularized chamber is a valuable tool for vascularizing implanted tissues and tissue-engineered constructs. Further optimization will be necessary to control the directional growth of vascular endothelial cells within the chamber and the vascularization grade. Impact Statement Vascularization of engineered tissue, or organoids, constructs is a major hurdle in tissue engineering. 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引用次数: 0
摘要
植入体外工程组织的一个主要障碍是纳入功能性血管供应,以支持新组织的生长并最大限度地减少缺血性损伤。现有的预血管化系统,如基于动静脉(AV)环的系统,需要进行显微手术,因此仅限于大型动物使用。我们的目标是开发一种可植入的装置,这种装置可以预血管化,实现小型啮齿动物组织的血管化,并测试其在胚胎肾脏血管化方面的应用。将腔室植入腹主动脉和下腔静脉之间,植入 48 小时后,我们检测到了内皮细胞和血管网络。用胶原蛋白I(C)、Matrigel(M)或Matrigel+血管内皮生长因子(VEGF)(MV)加载腔室对血管化速度有很大影响:装有 C 的细胞室需要 7 天才能形成血管,装有 M 的细胞室需要 4 天,装有 MV 的细胞室需要 2 天。将 E12.5 小鼠胚胎肾脏植入预先血管化的细胞室(C、MV)后,在 22 天内肾脏显著生长并形成输尿管分支。相比之下,未植入预血管室的肾脏生长缓慢。我们的结论是,我们的预血管化腔室是植入组织和组织工程构建物血管化的重要工具。有必要进一步优化,以控制腔体内血管内皮细胞的定向生长和血管化等级。
In Vivo Vascularization Chamber for the Implantation of Embryonic Kidneys.
A major obstacle to the implantation of ex vivo engineered tissues is the incorporation of functional vascular supply to support the growth of new tissue and to minimize ischemic injury. Existing prevascularization systems, such as arteriovenous (AV) loop-based systems, require microsurgery, limiting their use to larger animals. We aimed to develop an implantable device that can be prevascularized to enable vascularization of tissues in small rodents, and test its application on the vascularization of embryonic kidneys. Implanting the chamber between the abdominal aorta and the inferior vena cava, we detected endothelial cells and vascular networks after 48 h of implantation. Loading the chamber with collagen I (C), Matrigel (M), or Matrigel + vascular endothelial growth factor) (MV) had a strong influence on vascularization speed: Chambers loaded with C took 7 days to vascularize, 4 days for chambers with M, and 2 days for chambers with MV. Implantation of E12.5 mouse embryonic kidneys into prevascularized chambers (C, MV) was followed with significant growth and ureteric branching over 22 days. In contrast, the growth of kidneys in non-prevascularized chambers was stunted. We concluded that our prevascularized chamber is a valuable tool for vascularizing implanted tissues and tissue-engineered constructs. Further optimization will be necessary to control the directional growth of vascular endothelial cells within the chamber and the vascularization grade. Impact Statement Vascularization of engineered tissue, or organoids, constructs is a major hurdle in tissue engineering. Failure of vascularization is associated with prolonged ischemia time and potential tissue damage due to hypoxic effects. The method presented, demonstrates the use of a novel chamber that allows rapid vascularization of native and engineered tissues. We hope that this technology helps to stimulate research in the field of tissue vascularization and enables researchers to generate larger engineered vascularized tissues.
期刊介绍:
Tissue Engineering is the preeminent, biomedical journal advancing the field with cutting-edge research and applications that repair or regenerate portions or whole tissues. This multidisciplinary journal brings together the principles of engineering and life sciences in the creation of artificial tissues and regenerative medicine. Tissue Engineering is divided into three parts, providing a central forum for groundbreaking scientific research and developments of clinical applications from leading experts in the field that will enable the functional replacement of tissues.
Tissue Engineering Methods (Part C) presents innovative tools and assays in scaffold development, stem cells and biologically active molecules to advance the field and to support clinical translation. Part C publishes monthly.