Hypoxia-Perfusion Bioreactor for Stem Cell Applications

描述(由申请人提供)：脐带血(CB)细胞是移植的理想干细胞来源，因为它们的收集不会对捐赠者造成影响，而且它们将促进创建一个种族多样化的捐赠者细胞库。然而，少量的干细胞和广泛的红细胞减少与使用脐血细胞进行移植相关，限制了在成人患者中的广泛应用。能够扩大再生干细胞的体外方案已经开发出来，但需要数周的培养，以及增加污染风险和限制重复性的多种操作和血管的使用。为了利用低氧水平有利于干细胞扩增的最新发现，Resodyn公司开发了低氧-灌流生物反应器(HPB)，旨在提供对干细胞培养的氧气和新鲜培养液的受控输送。这项提案的目的是展示HPB作为一种简单、廉价的干细胞浓缩装置的用途，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来提高干细胞扩增的速度和质量。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，并将完成将方案和硬件扩大到临床就绪的系统。第三阶段将包括临床试验，以测试扩增干细胞的疗效。HPB系统无论是在实验室作为促进干细胞方案开发的工具，还是在临床作为脐带血移植和其他神经、造血和间充质系干细胞方案的组成部分，都具有巨大的长期商业潜力。

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.