Enhanced Bioprocessing Strategies for Human Mesenchymal Stem Cells

人类间充质干细胞的增强生物加工策略

基本信息

批准号：
8096921
负责人：
John M BAUST
金额：
$ 36.93万
依托单位：
CELL PRESERVATION SERVICES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8096921
关键词：
Address Adipose tissue Atrial Fibrillation Autologous Biological Preservation Biological Sciences Biology Biomedical Engineering Bone Marrow Canada Cell Count Cell Death Cell Differentiation process Cell Separation Cell Survival Cell Therapy Cell physiology Cells Cellular Stress Characteristics Chondrocytes Clinical Trials Cornea Cryosurgery Culture Media Development Devices Diabetes Mellitus Disease Drug Formulations Engineering Engraftment Event Exposure to Growth Heart Homing Human Human Resources Hypoxia Lead Liquid substance Malignant Neoplasms Medical Medical Device Mesenchymal Stem Cells Molecular Monitor Nitrogen Organ Osteoblasts Outcome Pathway Analysis Pathway interactions Phase Probability Process Reagent Research Role Scientist Series Site Solutions Source Staging Stem cells Stress System Technology Temperature Testing Therapeutic Tissue Engineering Tissues Transfusion base bioprocess cancer therapy cell type clinical application cold temperature design experience improved in vivo inhibitor/antagonist paracrine prevent programs prototype repaired research and development stem cell therapy success technology development

项目摘要

DESCRIPTION (provided by applicant): The results of early clinical trials using stem cells clearly offer the promise of a new path to addressing a variety of medical problems that range from creating engineered tissues for autologous grafts to repairing a variety of organs. Mesenchymal stem cells (MSCs) are especially attractive candidates for stem cell therapy given their documented characteristic of homing to the target tissue, ability to differentiate into a host of different cell types, and role as a paracrine source thus facilitating the repair and growth of neighboring cells. A notable problem with MSC therapy, however, is the well documented cell death (> 50%) that occurs upon isolation, processing and transfusion. This issue has led many groups to "prime" MSC prior to transfusion by transient exposure to stress regimes such as hypoxia. CPSI-Biotech is currently developing a series of culture reagents, CellGuard, that are designed to prevent the loss of cell viability and function of human cells during bioprocessing. This Phase 1 project is designed to develop CellGuard-MSC - a media supplement designed to protect MSC during isolation, processing and transfusion at normothermic temperatures so that both the cell number and differentiation potential are maintained in a more native state. CellGuard is cell and process specific and designed based on the identification and modulation of the key cell stress pathways that are activated in human cells during bioprocessing. Research outlined in this proposal will (1) determine which stress pathways are activated during MSC processing, (2) identify modulators of these pathways and (3) test a prototype CellGuard-MSC for its ability to maintain MSCs under conditions representative of bioprocessing and transfusion. Phase 2 will be focused on additional stem cell types used in cell therapy as well as further development and characterization of CellGuard-MSC. Source-specific MSCs such as adipose-derived, corneal-derived and bone marrow-derived MSCs will be included in the Phase 2 program. The successful completion of this project will result in an enhancement of MSC cell therapy through the development of a molecular "coat of armor" that will protect the integrity and differentiation potential of MSCs during cell isolation and processing. PUBLIC HEALTH RELEVANCE: This project is designed to conduct research that will lead to the development of a series of products, termed CellGuard, which 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 set of solutions that will protect human mesenchymal stem cells that are currently being used in a variety of stem cell applications ranging from cell therapy for the heart to treating diabetes.

描述（由申请人提供）：使用干细胞的早期临床试验的结果显然为解决各种医学问题提供了新途径，这些问题包括为自体移植物创建工程组织到修复各种器官。间充质干细胞 (MSC) 是干细胞治疗特别有吸引力的候选者，因为它们具有归巢到靶组织的特性、分化成多种不同细胞类型宿主的能力以及作为旁分泌源的作用，从而促进邻近细胞的修复和生长。细胞。然而，MSC 治疗的一个值得注意的问题是，在分离、处理和输注时发生的细胞死亡 (> 50%) 有据可查。这个问题导致许多团体在输血前通过短暂暴露于缺氧等应激状态来“启动”MSC。 CPSI-Biotech 目前正在开发一系列培养试剂 CellGuard，旨在防止人体细胞在生物加工过程中丧失细胞活力和功能。该第一阶段项目旨在开发 CellGuard-MSC——一种培养基补充剂，旨在在常温下的分离、处理和输注过程中保护 MSC，从而使细胞数量和分化潜力保持在更自然的状态。 CellGuard 是针对细胞和过程的，其设计基于对生物加工过程中人体细胞中激活的关键细胞应激途径的识别和调节。该提案中概述的研究将 (1) 确定哪些应激途径在 MSC 加工过程中被激活，(2) 识别这些途径的调节剂，以及 (3) 测试 CellGuard-MSC 原型在生物加工和输血代表条件下维持 MSC 的能力。第二阶段将重点关注细胞治疗中使用的其他干细胞类型以及 CellGuard-MSC 的进一步开发和表征。特定来源的 MSC，例如脂肪源性、角膜源性和骨髓源性 MSC，将纳入第二阶段计划。该项目的成功完成将通过开发分子“盔甲”来增强 MSC 细胞治疗，该分子“盔甲”将在细胞分离和加工过程中保护 MSC 的完整性和分化潜力。公共卫生相关性：该项目旨在进行研究，开发一系列名为 CellGuard 的产品，该产品将在操作过程中保护人体细胞。多种人类细胞类型现在被用于治疗癌症、糖尿病，并且还用作生物医学领域中使用的工程组织的构建模块。操纵人类细胞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在临床应用过程中遇到这些恶劣条件时。这个特殊项目旨在开发一套保护人类间充质干细胞的解决方案，这些干细胞目前用于各种干细胞应用，从心脏细胞疗法到治疗糖尿病。