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Decellularized extracellular matrix mediates tissue construction and regeneration

《医学前沿（英文）》 2022年第16卷第1期页码 56-82 doi: 10.1007/s11684-021-0900-3

摘要： Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell–matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

关键词： decellularized extracellular matrix 3D culture organoids tissue repair

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Liver cell therapies: cellular sources and grafting strategies

《医学前沿（英文）》 2023年第17卷第3期页码 432-457 doi: 10.1007/s11684-023-1002-1

摘要： The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver’s cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.

关键词： liver regeneration hepatocytes cholangiocytes stem cells organoids regulatory mechanisms transplantation/grafting strategies

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组织工程中肾脏血管化构建的领先方法 Review

Diana S. Lim, John D. Jackson, Anthony Atala, James J. Yoo

《工程（英文）》 2022年第19卷第12期页码 117-127 doi: 10.1016/j.eng.2022.05.004

摘要：

由于肾衰竭发病率升高的速度远超治疗方法进展的速度，因而对这种疾病的新的治疗方法的需求也以前所未有的速度不断增加。目前的治疗受制于可供应的活器官，而世界范围内均缺乏这种器官。这些治疗模式还需要大量的基础结构，这也极大地限制了大多数国家的患者获得医疗服务的机会。通过肾脏组织工程方法有望开发出替代的解决方案，解决目前治疗中仍存在的许多不足之处。尽管在生物制造和全器官组织工程方面已经取得了许多进展——主要是在过去的10 年中取得的，但仍然存在许多挑战。当前组织工程方法进展中的一个主要障碍是如何对已形成的工程化组织构建体实施成功的血管化。本文主要涉及近年来解决血管问题取得的进展，包括脉管系统的生物制造、通过脱细胞和再细胞化方法实施全器官工程、微尺度器官形成，以及在肾脏组织工程背景下使用类器官取得血管化。本文还着重探讨了在制定成功的临床转化策略中仍然存在的具体问题。

关键词：肾脏血管形成组织工程生物制造类器官