CellGuard-TD improves human tissue digestion and cell subculturing

CellGuard-TD 改善人体组织消化和细胞传代培养

• 批准号: 8249539
• 负责人: Robert G Van Buskirk
• 金额: $ 18.4万
• 依托单位: CELL PRESERVATION SERVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8249539
• 关键词: Adipose tissue; Agreement; Apoptosis; Area; Arrhythmia; Basic Science; Biological Preservation; Biological Sciences; Biology; Botanicals; Cell Culture Techniques; Cell Separation; Cell Survival; Cell Therapy; Cell physiology; Cells; Cellular Stress; Culture Media; Development; Diabetes Mellitus; Digestion; Disease; Drug Formulations; Elements; Engineering; Environment; Event; Foundations; Growth; Health; Human; Human Characteristics; Human Resources; Investigation; Islet Cell; Islets of Langerhans; Lead; Legal patent; Letters; Malignant Neoplasms; Marketing; Medical Device; Mesenchymal Stem Cells; Methods; Molecular; Molecular Biology; Pancreas; Pathway interactions; Patients; Pharmacologic Substance; Phase; Procedures; Process; Protocols documentation; Publications; Reagent; Research; Series; Solutions; Source; Stem cell transplant; Stem cells; Stress; System; Technology; Temperature; Testing; Therapeutic; Tissue Engineering; Tissues; Transfusion; Warm Ischemia; Work; arm; base; bioprocess; cancer stem cell; cell type; clinical application; cold temperature; collagenase; design; experience; human tissue; hypothermosol; implantation; improved; improved functioning; inhibitor/antagonist; islet; neglect; novel; phase 1 study; phase 2 study; prototype; technology development

DESCRIPTION (provided by applicant): Tissue digestion and cell extraction is a core element of a variety of bioprocessing methods ranging from isolation of the rare cancer stem cell for basic research to the purification of human islets or adipose-derived mesenchymal stem cells for transplant. While procedures vary, it is clear that each tissue digestion procedure subjects the intact tissue to cell stress that can result in a loss of cell viability and function. CPSI-Bioech is focused on improving the bioprocessing of a variety of human cell types at normothermic temperatures (20 to 370C) so that their pharmacological and cell therapy utility can be improved. To this end the Company is developing the CellGuard supplement series - reagents that when added to select bioprocessing procedures will protect and maintain cell viability and function. This, in turn, will lead to fewer post-graft or transfusion problems in the patient. This Phase 1 project proposes to develop CellGuard-TD - a supplement designed to enhance tissue digestion (TD) of human pancreatic tissue for islet isolation (CTDislet). Phase 1 will use a variety of molecular biology methods to develop a prototype CTDislet- the first supplement designed to improve pancreatic islets digestion through cell stress pathway modulation. CTDislet will be based on the well documented apoptosis-prone nature of human pancreatic islets, their low cell yield as a result of warm ischemia exposure, and the collagenase-induced damage to islets that results in a low number obtained from each pancreas. Phase 2 studies will be dedicated to a more in depth analysis and development of CTDislet as well as testing this new formulation at select islets procurement centers. A second aim of the Phase 2 studies will be the development of a "non-synthetic" CTDislet formulation comprised of cell stress inhibitors derived from botanical sources. The intent of this project is to develop a supplement that protects the fragile nature of human pancreatic islets during the isolation and handling process- a technology that will apply to native islets as well as islets differentiated from mesenchymal stem cells and other stem cell sources. The human health consequence of this research will be to improve the isolation, handling and transfusion of human islets used for treating diabetes. PUBLIC HEALTH RELEVANCE: This project is designed to conduct research that will lead to the development of a series of products, termed CellGuard that will protect human cells during manipulation. A variety of human cell types are now being used to treat cancer, diabetes, and also serve as the building blocks of engineered tissues used in the biomedical field. Manipulating human cells such that they can be used for these purposes often compromises both cell function and viability. The CellGuard portfolio of products is designed to protect these cells when they are subjected to these harsh conditions on the path for clinical application. This particular project is designed to develop a CellGuard supplement that will improve the isolation and cell therapy application of human pancreatic islets leading to improved methods for treating diabetes.

描述（由申请人提供）：组织消化和细胞提取是各种生物处理方法的核心要素，范围从用于基础研究的罕见癌症干细胞的分离到用于移植的人胰岛或脂肪来源的间充质干细胞的纯化。虽然程序不同，但很明显，每个组织消化程序都会使完整组织受到细胞应激，这可能导致细胞活力和功能丧失。CPSI-Bioech专注于在常温（20至370 ℃）下改善各种人类细胞类型的生物加工，从而提高其药理学和细胞治疗效用。为此，该公司正在开发CellGuard补充系列-当添加到选择的生物处理程序将保护和维持细胞活力和功能的试剂。这反过来又会导致患者更少的移植后或输血问题。这 1期项目拟开发CellGuard-TD -一种旨在增强人胰腺组织的组织消化（TD）以进行胰岛分离（CTDislet）的补充剂。第一阶段将使用各种分子生物学方法开发CTDislet原型-第一种旨在通过细胞应激途径调节改善胰岛消化的补充剂。CTDislet将基于有充分记录的人类胰岛的易变性性质、热缺血暴露导致的低细胞产量以及胶原酶诱导的胰岛损伤（导致从每个胰腺获得的数量较少）。第2阶段研究将致力于更深入地分析和开发CTDislet，并在选定的胰岛采购中心测试这种新制剂。第二阶段研究的第二个目标是开发一种“非合成”CTDislet制剂，由植物来源的细胞应激抑制剂组成。该项目的目的是开发一种补充剂，在分离和处理过程中保护人类胰岛的脆弱性-该技术将适用于天然胰岛以及从间充质干细胞和其他干细胞来源分化的胰岛。这项研究对人类健康的影响将是改善用于治疗糖尿病的人类胰岛的分离、处理和输血。 公共卫生相关性：该项目旨在进行研究，以开发一系列产品，称为CellGuard，可在操作过程中保护人体细胞。各种人类细胞类型现在被用于治疗癌症，糖尿病，并作为生物医学领域中使用的工程组织的构建块。操纵人类细胞以使其可用于这些目的通常会损害细胞功能和活力。CellGuard产品组合旨在保护这些细胞，当它们在临床应用的道路上受到这些恶劣条件的影响时。这个特殊的项目旨在开发一种CellGuard补充剂，它将改善人类胰岛的分离和细胞治疗应用，从而改善治疗糖尿病的方法。