A perfluorocarbon-based culture device for beta cell biology applications

用于 β 细胞生物学应用的基于全氟化碳的培养装置

• 批准号: 7672945
• 负责人: Ramon E. Poo
• 金额: $ 10万
• 依托单位: BIOREP TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-10 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672945
• 关键词: Academia; Address; Adult; Air; Animals; Anoxia; Arts; Basic Science; Beta Cell; Biological Models; Biology; Blood flow; Bone Marrow; Cardiac Myocytes; Cell Count; Cell Culture Techniques; Cell Differentiation process; Cell Line; Cell Survival; Cell Therapy; Cell physiology; Cells; Cellular biology; Cessation of life; Clinical; Culture Media; Custom; Data; Development; Devices; Diabetes Mellitus; Diabetic mouse; Diffusion; Discipline; Ensure; Equilibrium; Equipment; Explosion; Fluorocarbons; Future; Glucose; Goals; Growth; Hepatocyte; Homeostasis; Human; Hyperoxia; Hypoxia; Immunocompromised Host; Immunodeficient Mouse; In Vitro; Individual; Industry; Intervention; Islet Cell; Islets of Langerhans; Islets of Langerhans Transplantation; Joints; Knowledge; Laboratories; Legal patent; Length; Link; Marketing; Measures; Medical; Membrane; Methods; Mission; Modeling; Molecular Biology Techniques; National Institute of Diabetes and Digestive and Kidney Diseases; Organ; Outcome; Oxygen; Pancreas; Phase; Phase II Clinical Trials; Physicians; Physiological; Plastics; Preparation; Process; Production; Public Health; Qualifying; Research; Research Design; Research Institute; Research Personnel; Role; Silicones; Stem Cell Research; Stem cells; Streptozocin; Structure of beta Cell of islet; System; Technology; Temperature; Testing; Time; Training; Translating; Translational Research; Transplantation; Universities; Variant; Xenograft procedure; base; clinically significant; commercialization; design; diabetes mellitus therapy; diabetic; experience; feeding; fetal; immortalized cell; improved; interest; islet; islet stem cells; multidisciplinary; novel; pre-clinical; prevent; prospective; prototype; public health relevance; stem cell differentiation; success; tissue culture; tissue/cell culture; tool

DESCRIPTION (provided by applicant): Conventional culture vessels are not designed for physiological oxygen delivery. Both hyperoxia and hypoxia -commonly observed when culturing cells and tissues in regular plastic ware- have been linked to reduced cellular function and death. This is particularly true of pancreatic beta cells, which are highly sensitive to sub- and super-physiological oxygen concentrations. We have addressed this problem by devising a novel culture device, the "oxygen sandwich". This simple system is designed to deliver oxygen in a physiological-like fashion by means of a basal air-permeable perfluorocarbon-silicone (PFC/Si) membrane. Our long-term goal is to establish this system as the new culture standard for beta cell biology applications, a rapidly expanding market that includes in vitro research on adult/fetal islets of any species, as well as beta cell differentiation studies. In this context, the specific aim of this Phase I proposal is to establish proof of concept that the enhanced in vitro survival and function observed in PFC/Si-cultured islets results in better pre-clinical transplantation outcomes. Our research design is based on a marginal mass xenotransplantation model (human islets into diabetic nu/nu immunodeficient mice), where the potential benefits of PFC/Si culture prior to transplantation should translate into a shorter time to diabetes reversal compared to animals transplanted with control (regular culture) islets. Our initial results are strongly supportive of the feasibility of this proposal, and we have partnered with the Diabetes Research Institute at the University of Miami to accomplish our goals in a timely manner. Success in our research would fill a widely acknowledged gap in our ability to preserve islet cell function and survival in vitro, confirming this system as a potential new standard for beta cell biology and differentiation studies. Such positive outcome would be highly relevant to the mission of the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), and might ultimately be of clinical significance for human islet/beta cell transplantation. PUBLIC HEALTH RELEVANCE: Beta cell research is a large field where basic science interest is further fueled by current (islet transplantation) and prospective (stem cells and xenotransplantation) clinical therapies for diabetes. However, beta cell studies are compromised by the inability of conventional culture systems to provide physiological oxygenation. Since our proposal aims at testing a novel culture device specifically designed to overcome this problem, these studies are highly relevant to the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and may ultimately have a significant impact on public health.

描述（由申请人提供）：常规培养容器不适用于生理氧气输送。在普通塑料器皿中培养细胞和组织时，通常会观察到高氧和缺氧，这两者都与细胞功能降低和死亡有关。胰腺β细胞尤其如此，其对亚生理和超生理氧浓度高度敏感。我们通过设计一种新的培养装置“氧气三明治”来解决这个问题。这个简单的系统设计用于通过基础透气的全氟化碳-硅（PFC/Si）膜以类似生理的方式输送氧气。我们的长期目标是将该系统建立为β细胞生物学应用的新培养标准，这是一个迅速扩大的市场，包括对任何物种的成人/胎儿胰岛的体外研究以及β细胞分化研究。在这种情况下，该I期提案的具体目的是建立概念证明，即在PFC/Si培养的胰岛中观察到的体外存活和功能增强导致更好的临床前移植结局。我们的研究设计是基于一个边缘质量异种移植模型（人类胰岛移植到糖尿病nu/nu免疫缺陷小鼠），其中PFC/Si文化移植前的潜在利益应转化为一个较短的时间糖尿病逆转相比，动物移植对照（常规文化）胰岛。我们的初步结果强烈支持这一提议的可行性，我们已与迈阿密大学糖尿病研究所合作，以及时实现我们的目标。我们研究的成功将填补我们在体外保存胰岛细胞功能和存活能力方面的一个广泛公认的空白，证实该系统是β细胞生物学和分化研究的潜在新标准。这种积极的结果将是高度相关的使命的国立糖尿病和消化和肾脏疾病研究所（NIDDK），并可能最终是临床意义的人胰岛/β细胞移植。公共卫生相关性：β细胞研究是一个大的领域，其中基础科学的兴趣进一步受到当前（胰岛移植）和前瞻性（干细胞和异种移植）糖尿病临床疗法的推动。然而，β细胞研究受到常规培养系统无法提供生理氧合的影响。由于我们的提案旨在测试一种专门设计用于克服这一问题的新型培养装置，因此这些研究与国家糖尿病、消化和肾脏疾病研究所（NIDDK）的使命高度相关，并可能最终对公共卫生产生重大影响。