High Cell Density Bioartificial Pancreas Enabled by Implantable Oxygen Generator

植入式氧气发生器实现高细胞密度生物人工胰腺

• 批准号: 8633290
• 负责人: KLEARCHOS K PAPAS
• 金额: $ 22.49万
• 依托单位: GINER, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8633290
• 关键词: Address; Allogenic; Animal Model; Animals; Arizona; Biocompatible; Blood Glucose; Cell Density; Cell Therapy; Cells; Characteristics; Clinical; Clinical Trials; Construction Materials; Custom; Devices; Diabetes Mellitus; Effectiveness; Electrodes; Electrolyses; Electronics; Energy Transfer; Engineering; Environment; Evaluation; Family suidae; Generations; Glucose; Goals; Hemophilia A; Housing; Human; Immunohistochemistry; Immunology; Immunosuppression; Implant; Implantation procedure; In Situ; In Vitro; Insulin; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans; Liver Failure; Measurement; Membrane; Modeling; Nude Rats; Oxygen; Oxygen Consumption; Pancreas; Pancreatitis; Paper; Parkinson Disease; Patients; Performance; Phase; Power Sources; Production; Readiness; Saline; Series; Site; Small Business Innovation Research Grant; Stem cells; System; Technology; Testing; Therapeutic; Thyroid Diseases; Tissues; Transplantation; Universities; Work; base; cancer diagnosis; cell type; clinical application; density; design; diabetic; experience; graft function; implantable device; in vitro testing; in vivo; insulin secretion; islet; liver transplantation; meetings; miniaturize; multidisciplinary; next generation; prototype; public health relevance; research study; sensor; voltage; water vapor

DESCRIPTION (provided by applicant): The overall goal of this proposed SBIR project is to develop a miniaturized implantable oxygen generator that will continuously supply oxygen to cells within an immunoisolation cell implant device. This will maintain cellular viability and function at high cell densities thus minimizing overall implant size. The oxygen generator will be powered by a remotely rechargeable battery. The first proposed application of this platform technology is pancreatic islet implant for the treatment of Type 1 diabetes (T1D). The combination of the oxygenator with a well-characterized immunoisolation device is termed a bioartificial pancreas with implantable oxygen supply (BAPIOS). The implantable oxygen generator is also a platform technology that could be combined with other cell implant devices and other therapeutic cell types for other cellular therapies for conditions such as liver failure, Parkinson's disease, (para)thyroid disease and hemophilia. Pancreatic islet allotransplantation is in U.S. clinical trials. There are also results from leading centers demonstrating insulin independence for more than 5 years for 50% of the recipients. However, widespread clinical application of for T1D is hindered by two critical barriers: 1) the need for systemic immunosuppression for the current intraportal liver transplant site; and 2) by the finite and low supply of human islet tissue (a few thousand suitable donors per year). The use of biocompatible, retrievable, cell isolating devices may address these critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression and the eventual use of stem cell-derived or xenogeneic islets with minimum or no immunosuppression. Autotransplantation (for pancreatitis patients and pre-cancer diagnosis) could also benefit from a simple implant procedure with retrievability and cellular immunoisolation. Current cell implant devices have insufficient oxygen (even with prevascularization of the device) to provide the high cellular densities required for practically-sized clinical implants. The proposed technology would include the first implantable, continuous oxygen supply with integrated rechargeable battery. The Specific Aims of the 12 month Phase I project are: Aim 1: Design and fabrication of a miniature oxygen generator (oxygenator); Aim 2: In vitro evaluation of the Ph I miniature oxygenator and the oxygenated implant device; Aim 3: Preliminary in vivo testing in a diabetic nude rat model; and Aim 4: Design of complete bioartificial pancreas with implantable oxygen supply (BAPIOS) for implementation in Ph II. This aim includes a fully implantable oxygenator as well as customization of the cell implant device for this application. This Ph I feasibility stuy will provide the groundwork for final design and fabrication of a fully implantable oxygenated cell implant in Phase II and large animal studies ultimately leading to the treatment of T1D in humans.

描述(由申请人提供)：这个建议的SBIR项目的总体目标是开发一种微型可植入氧气发生器，该发生器将持续向免疫隔离细胞植入设备内的细胞供应氧气。这将在高细胞密度下保持细胞的活性和功能，从而最小化整体种植体的大小。氧气发生器将由远程充电电池供电。该平台技术的第一个拟议应用是用于治疗1型糖尿病(T1D)的胰岛移植。氧合器与免疫隔离装置的结合被称为具有植入性供氧的生物人工胰腺(BAPIOS)。植入式氧气发生器也是一种平台技术，可以与其他细胞植入设备和其他治疗细胞类型相结合，用于其他细胞疗法，如肝功能衰竭， 帕金森氏症、甲状腺疾病和血友病。同种异体胰岛移植正在美国进行临床试验。领先中心的结果也表明，50%的受试者胰岛素独立超过5年。然而，For T1D的广泛临床应用受到两个关键障碍的阻碍：1)当前门静脉内肝移植部位需要全身性免疫抑制；2)人类胰岛组织的有限和低供应(每年数千名合适的供者)。使用生物兼容、可回收的细胞分离设备可以解决这些关键障碍，方法是在没有免疫抑制的情况下更有效和高效地使用同种异体胰岛，并最终使用免疫抑制最低或没有免疫抑制的干细胞来源的或异种胰岛。自体移植(用于胰腺炎患者和癌症前诊断)也可以受益于具有可恢复性和细胞免疫隔离的简单植入程序。目前的细胞植入设备没有足够的氧气(即使在设备预血运的情况下)，无法提供实际大小的临床植入所需的高细胞密度。这项拟议的技术将包括第一个可植入的、带有集成充电电池的连续氧气供应。为期12个月的第一阶段项目的具体目标是：目标1：设计和制造微型氧气发生器(氧合器)；目标2：对Ph I微型氧合器和充氧植入器进行体外评估；目标3：在糖尿病裸鼠模型上进行初步体内测试；以及目标4：设计完整的具有植入性供氧的生物人工胰腺(BAPIOS)，以便在Ph II实施。这一目标包括一个完全可植入的氧合器以及为此应用定制的细胞植入装置。这项PHI可行性研究将为最终设计和制造完全可植入的充氧电池奠定基础 第二阶段的植入和大型动物研究最终导致了人类T1D的治疗。