开发肾脏祖细胞器官组织并在肾脏内输送,以实现体内有效整合。

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cells Translational Medicine Pub Date : 2024-10-28 DOI:10.1093/stcltm/szae078
Diana Lim, Ickhee Kim, Qianqian Song, Ji Hyun Kim, Anthony Atala, John D Jackson, James J Yoo
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引用次数: 0

摘要

肾脏祖细胞器官组织已被提出作为肾脏再生的组织来源;然而,由于无法大规模生产全面的肾脏祖细胞器官组织,以及缺乏有效的肾脏内输送平台以促进快速整合到有功能意义的部位,它们的临床可转化性尚未得到证实。本研究弥补了这些不足。采用既定方案将人类诱导多能干细胞分化成肾脏祖细胞,并采用新颖的组装方法将其聚集,以生产高产量的器官组织。有机体被封装在胶原基支架中,用于体外研究和体内植入小鼠肾皮质。在体外,随着时间的推移,器官组织显示出持续的细胞活力和肾脏结构成熟。体内输送的类器官显示出与宿主肾实质的快速整合,同时显示出肾小管和肾小球样结构的发育和成熟标志。这项概念验证研究提出了许多有前景的结果,提供了一个肾脏类器官形成和输送系统,可支持开发可临床转化的疗法和推进体外肾脏类器官研究。
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Development and intra-renal delivery of renal progenitor organoids for effective integration in vivo.

Renal progenitor organoids have been proposed as a source of tissue for kidney regeneration; however, their clinical translatability has not been demonstrated due to an inability to mass-produce comprehensive renal progenitor organoids and the lack of an effective intra-renal delivery platform that facilitates rapid integration into functionally meaningful sites. This study addresses these shortcomings. Human-induced pluripotent stem cells were differentiated into renal progenitor cells using an established protocol and aggregated using a novel assembly method to produce high yields of organoids. Organoids were encapsulated in collagen-based scaffolds for in vitro study and in vivo implantation into mouse renal cortex. In vitro, the organoids demonstrated sustained cell viability and renal structure maturation over time. In vivo delivered organoids showed rapid integration into host renal parenchyma while showing tubular and glomerular-like structure development and maturity markers. This proof-of-concept study presents many promising results, providing a system of renal organoid formation and delivery that may support the development of clinically translatable therapies and the advancement of in vitro renal organoid studies.

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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
期刊最新文献
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