Hypoxia-Perfusion Bioreactor for Stem Cell Applications

描述（由申请人提供）：这个小企业创新研究第一阶段项目将开发和演示一个原型缺氧灌注生物反应器（HPB）。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HPB，旨在为干细胞培养提供可控的氧气和新鲜培养基。研究和控制物理参数是必要的，以便为临床带来可复制的，经济上可行的治疗。该II期提案的目标之一是评估和证明Resodyn公司的低氧灌注生物反应器（HPB）在广泛的造血细胞扩增应用中的实用性和商业可行性。第二个目标是开发一个模型方案，该方案将证明HPB在不需要预先选择原始干细胞群体（CD34+或AC133+）的情况下扩增造血干细胞（hsc）的能力。这种能力在降低干细胞领域治疗和研究的成本和复杂性方面取得了重大进展。虽然HPB的主要可行性将主要在造血细胞群中进行测试，但该设备的优点（控制缺氧/氧气水平，高细胞密度，减少人工，降低污染风险）将扩展到其他类型的干细胞和祖细胞（间充质细胞，脂肪细胞，神经细胞等），以及用于一般哺乳动物细胞培养。这些应用包括用于生产单克隆抗体（MAb）的杂交瘤培养和用于生产重组蛋白的中国仓鼠卵巢（CHO）细胞培养。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，还是在临床中作为造血移植和其他神经、造血和间充质谱系的干细胞治疗的组成部分。公共卫生相关性：这个小企业创新研究第一阶段项目将开发和演示一个缺氧灌注生物反应器（HPB）。HPB是一种专为干细胞和其他原代细胞培养而设计的一次性生物反应器，可以大大降低人工成本，降低与细胞治疗扩大相关的污染风险。HPB将降低成本，并简化干细胞疗法从研究实验室到临床的转化。

DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project will develop and demonstrate a prototype Hypoxia Perfusion Bioreactor (HPB). In order to utilize recent discoveries that low oxygen levels are favorable to stem cell expansion, Resodyn Corporation has developed the HPB, which is designed to provide controlled delivery of both oxygen and fresh medium to stem cell cultures. Studying and controlling the physical parameters are essential in order to bring reproducible, economically feasible therapies to the clinic. One goal of this Phase II proposal is to evaluate and demonstrate the utility and commercial feasibility of Resodyn Corporation's Hypoxia Perfusion Bioreactor (HPB) for wide range of hematopoietic cell expansion applications. A second goal is to develop a model protocol that will demonstrate the HPB's ability to expand hematopoietic stem cells (HSCs) without the requirement for previous selection (CD34+ or AC133+) for primitive stem cell populations. This capability would represent a significant advance in reducing the cost and complexity of therapeutic and research efforts in the stem cell field. While the primary feasibility of the HPB will be tested primarily with hematopoietic cell populations, the benefits of this device (controlled hypoxia/oxygen levels, high cell densities, reduced labor, lower contamination risk) would have extended utility to other types of stem and progenitor cells (mesenchymal, adipose, neural, etc.), as well as for use in general mammalian cell culture. Such applications include hybridoma culture for monoclonal antibody (MAb) production and Chinese Hamster Ovary (CHO) cell culture for production of recombinant proteins. 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 hematopoietic transplantation and other pre-emerging stem cell therapies of the neural, hematopoietic, and mesenchymal lineages. PUBLIC HEALTH RELEVANCE: This Small Business Innovation Research Phase I project will develop and demonstrate a Hypoxia Perfusion Bioreactor (HPB). The HPB is a single-use bioreactor designed specifically for stem cell and other primary cell cultures and can substantially reduce labor costs and reduce contamination risks associated with the scale-up of cellular therapies. The HPB will reduce costs and ease the translation of stem cell therapies from the research lab to the clinic.