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Organogenesis in microcapsules: developing an efficient and scalable organoid culture platform

微胶囊中的器官发生：开发高效且可扩展的类器官培养平台

基本信息

批准号：
8952452
负责人：
Minglin Ma
金额：
$ 7.21万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8952452
关键词：
Alginates Area Biological Biological Models Bioreactors Cell Count Cells Clinical Collagen Computers Deposition Development Disease model Dissociation Drops Drug Formulations Electrostatics Emerging Technologies Encapsulated Environment Extracellular Matrix Goals Growth Harvest Hydrogels In Vitro Intestines Laboratories Letters Manuals Mechanics Methods Microcapsules drug delivery system Monitor Mus Names Organ Organogenesis Organoids Outcomes Research Play Pluripotent Stem Cells Process Production Research Role Sampling Stem cells Stress Structure Surface Suspension Culture System Technology Testing Therapeutic Tissues Translations base clinical application clinically relevant drug testing flasks high throughput screening intestinal crypt large scale production matrigel progenitor public health relevance research study scale up stem stem cell biology tissue culture

项目摘要

DESCRIPTION: The objective of this project is to develop an efficient and scalable organoid culture platform using core-shell decoupled hydrogel microcapsules. Organoids, organ-mimicking multicellular structures derived from pluripotent stem cells or organ progenitors, have recently emerged as an important system for both studies of fundamental stem cell biology and development of potential therapeutics. Research groups worldwide have made important progress in deriving organoids for various organs; however large-scale culture or production of organoids, a prerequisite for their industrial and clinical applications, has remained a challenge. Current organoid culture systems by embedding the stem or progenitor cells in bulk extracellular matrix (ECM) hydrogels have limited surface area for mass transfer and are not suitable for large-scale productions. We propose to develop a microcapsule-based, scalable organoid culture platform. The microcapsules have a core-shell structure where the core consists of ECM that supports the growth of the organoids and the shell forms robust spherical microcapsules, enabling suspension culture in stirred bioreactors. Compared with conventional culture in bulk ECM hydrogels, the microcapsules have a much higher surface-to-volume ratio for mass transfer and can be produced continuously at a large rate (>10,000/min) by a two-fluidic electrostatic cospraying. The anticipated outcome of this research is the development of a new organoid culture method that will not only facilitate the studies currently performed in numerous research groups but also accelerate and contribute to the translation of organoid technologies.

描述：本项目的目标是开发一种使用核壳解偶联水凝胶微胶囊的高效和可扩展的类有机物培养平台。类有机物是从多能干细胞或器官前体细胞中衍生出来的模拟器官的多细胞结构，近年来已成为基础干细胞生物学研究和潜在治疗药物开发的重要系统。世界各地的研究小组在为各种器官衍生有机化合物方面取得了重要进展，但作为其工业和临床应用的先决条件的有机化合物的大规模培养或生产仍然是一个挑战。现有的将干细胞或祖细胞包埋在细胞外基质水凝胶中的类有机物培养体系，传质表面积有限，不适合规模化生产。我们建议开发一个基于微胶囊的、可扩展的有机化合物培养平台。微囊具有核壳结构，其中核心由支持有机物生长的ECM组成，壳层形成坚固的球形微囊，从而能够在搅拌生物反应器中进行悬浮培养。与传统的块状ECM水凝胶培养相比，该微胶囊具有更高的传质表面积比，并且可以通过双流体静电共喷雾以较高的速率(~gt；10,000/min)连续生产。这项研究的预期结果是开发一种新的有机培养方法，不仅将促进目前在许多研究小组中进行的研究，而且还将加速和促进有机技术的转化。