Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation.
Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation.
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DOI：
10.1016/j.celrep.2018.03.123
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发表时间：
2018-05-08
期刊：
影响因子：
8.8
通讯作者：
Taniguchi H
中科院分区：
文献类型：
--
作者：
Takahashi Y;Sekine K;Kin T;Takebe T;Taniguchi H
包括胰岛在内的组织碎片的临床移植面临着严峻的挑战，因为缺乏通过及时整合血管网络来确保有效植入的有效策略。我们最近通过基于间充质细胞依赖性收缩的“自凝聚”培养开发了一种复杂的类器官工程方法，从而使包括内皮细胞在内的解离异型谱系以时空方式自组织。在这里，我们报告了这种方法的成功适应，用于从来自各种器官（包括胰岛）的不同组织碎片生成复杂组织。人和小鼠胰岛与内皮细胞的自凝聚不仅促进了培养中的功能化，而且大大改善了移植后的植入。在治疗上，与传统方法相比，血管化胰岛移植更有效地治疗暴发性糖尿病小鼠。考虑到与3D组织治疗相关的移植后血管化的一般限制，我们的方法提供了一种在治疗性组织移植的背景下提高疗效的有前途的方法。Takahashi等报道了从人类和小鼠中产生血管化胰岛组织。移植后，血管化胰岛显著提高糖尿病小鼠的存活率，表明与常规胰岛移植相比，血糖快速恢复正常。
Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by “self-condensation” culture based on mesenchymal cell-dependent contraction, thereby enabling dissociated heterotypic lineages including endothelial cells to self-organize in a spatiotemporal manner. Here, we report the successful adaptation of this method for generating complex tissues from diverse tissue fragments derived from various organs, including pancreatic islets. The self-condensation of human and mouse islets with endothelial cells not only promoted functionalization in culture but also massively improved post-transplant engraftment. Therapeutically, fulminant diabetic mice were more efficiently treated by a vascularized islet transplant compared with the conventional approach. Given the general limitations of post-transplant vascularization associated with 3D tissue-based therapy, our approach offers a promising means of enhancing efficacy in the context of therapeutic tissue transplantation. Takahashi et al. report on generating vascularized islet tissue from humans and mice. After transplantation, vascularized islets significantly improve survival of diabetic mice, demonstrating the quick normalization of blood glucose compared with conventional islet transplantation.
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影响因子：
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