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）细胞是移​​植的干细胞的理想来源，因为它们的收集不构成供体影响，它们会促进创建种族多样化的供体细胞池。然而，与使用CB细胞用于移植的少量干细胞和扩展的细胞质相关，限制了对成年患者的广泛应用。已经开发了能够扩大重型干细胞的体内协议，但需要进行数周的培养，并使用多种操纵和血管，以增加污染的风险并限制可重复性。为了利用近期发现低氧水平有利于干细胞膨胀的发现，Resodyn Corporation开发了低氧 - 灌注生物反应器（HPB），该病情旨在提供氧气和新鲜培养基到干细胞培养物的控制递送。该提案的目的是证明将HPB用作简单，廉价的干细胞富集装置，以及可以使用当前最新的扩展协议来提高干细胞扩展的速率和质量的干细胞扩展装置。在第一阶段，将证明可行性并确定最佳氧气水平。在第二阶段，将探索细胞因子/氧相互作用，并将完成对临床准备就绪系统的方案和硬件的规模。第三阶段将由临床试验组成，以测试扩展的干细胞的功效。 HPB系统在实验室中具有巨大的长期商业潜力，作为促进干细胞方案开发的工具，以及在诊所中，作为CB移植的组成部分，以及神经，造血和间质谱系的其他预生气的干细胞方案。