Hypoxia-Perfusion Bioreactor for Stem Cell Applications

用于干细胞应用的缺氧灌注生物反应器

• 批准号: 6832955
• 负责人: TODD A MCADAMS
• 金额: $ 15.51万
• 依托单位: RESODYN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-14 至 2006-10-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832955
• 关键词: CD34 molecule; NOD mouse; SCID mouse; bioreactors; cell death; cell differentiation; cell proliferation; clinical research; cord blood; cytokine; human tissue; hypoxia; oxygen; perfusion; stem cells; technology /technique development; tissue /cell culture

DESCRIPTION (provided by applicant): Cord blood (CB) cells are a desirable source of stem cells for transplantation because their collection poses no donor impact and they would facilitate the creation of an ethnically diverse pool of donor cells. However, the small quantity of stem cells and the extended cytopenias associated with the use of CB cells for transplantation limit broad application to adult patients. Ex vivo protocols that enable expansion of repopulating stem cells have been developed, but require many weeks of culture, and the use of multiple manipulations and vessels that increase the risk of contamination and limit reproducibility. In order to utilize recent discoveries that low oxygen levels are favorable to stem cell expansion, Resodyn Corporation has developed the hypoxia-perfusion bioreactor (HPB), which is designed to provide controlled delivery of both oxygen and fresh medium to stem cell cultures. It is the aim of this proposal to demonstrate use of the HPB as a simple, inexpensive stem cell enrichment device, and as a stem cell expansion device that can increase the rate and quality of stem cell expansion using current state-of-the-art expansion protocols. In Phase I, feasibility will be demonstrated and the optimal oxygen levels established. In Phase II, cytokine/oxygen interactions will be explored, and a scale-up of protocols and hardware to a clinically-ready system will be accomplished. Phase III will consist of clinical trials to test the efficacy of expanded stem cells. The HPB system has significant long-term commercial potential both in the laboratory as a tool to facilitate development of stem cells protocols, and in the clinic as a component of both CB transplantation and other pre-emerging stem cell protocols of the neural, hematopoietic, and mesenchymal lineages.

描述（由申请人提供）：脐带血（CB）细胞是一种理想的干细胞移植来源，因为它们的收集不会对供体产生影响，而且它们有助于建立一个种族多样化的供体细胞库。然而，干细胞数量少以及与使用CB细胞进行移植相关的大量细胞减少限制了在成人患者中的广泛应用。已经开发出能够扩增再生干细胞的离体方案，但需要数周的培养，并且使用多种操作和血管，这增加了污染的风险并限制了可重复性。为了利用最近发现的低氧水平有利于干细胞增殖，Resodyn公司开发了低氧灌注生物反应器（HPB），旨在为干细胞培养提供可控的氧气和新鲜培养基。本提案的目的是证明HPB作为一种简单、廉价的干细胞富集装置的使用，以及作为一种干细胞扩增装置，可以使用当前最先进的扩增方案提高干细胞扩增的速率和质量。在第一阶段，将论证可行性并确定最佳氧气水平。在第二阶段，将探索细胞因子/氧的相互作用，并将完成方案和硬件的规模扩大到临床就绪的系统。第三阶段将包括临床试验，以测试扩展干细胞的功效。HPB系统具有重要的长期商业潜力，无论是在实验室中作为促进干细胞方案开发的工具，还是在临床中作为CB移植和其他神经、造血和间充质谱系的早期干细胞方案的组成部分。