Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation. Mus musculus

Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine. Overall design: Gene expression profiles of development-related gene expression in kidney bud transplants and murine kidneys.

本研究展示了一种通用方法，可通过将多能干细胞（pluripotent stem cell）诱导的组织特异性祖细胞，或相关组织样本，与内皮细胞及间充质干细胞（mesenchymal stem cells, MSCs）相结合，从多种组织中构建器官芽。间充质干细胞可触发此类异型细胞混合物发生凝聚，且该过程依赖于底物基质的刚度。确定最优力学特性后，可从肾、胰腺、肠、心脏、肺及脑等组织中构建出可移植的三维器官芽。移植后的胰腺及肾器官芽可快速实现血管化，并自组织为具备功能的组织特异性结构。本研究结果提供了一种通用平台，可通过调控力学特性生成血管化的复杂器官芽，在再生医学领域拥有广泛应用前景。实验设计：肾器官芽移植物与小鼠肾脏中发育相关基因的表达谱分析。