Technology platform for development of multi-component preservation solution

多组分保存解决方案开发技术平台

• 批准号: 8582171
• 负责人: ALLISON HUBEL
• 金额: $ 21.52万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8582171
• 关键词: Address; Adverse event; Algorithms; Amino Acids; Arrhythmia; Biological Preservation; Bone necrosis; Cardiovascular Diseases; Cartilage; Categories; Cell Membrane Structures; Cell Therapy; Cell physiology; Cells; Chills; Chronic Obstructive Airway Disease; Clinical; Clinical Research; Clinical Trials; Computational algorithm; Computer Simulation; Connective Tissue Diseases; Cryopreservation; Cryoprotective Agents; Defect; Dehydration; Development; Diabetes Mellitus; Dimethyl Sulfoxide; Disease; Dose; Droughts; Dyspnea; Environment; Failure; Freezing; Growth; Heart; Heart Arrest; Hematopoietic stem cells; Human; Hydration status; Hypotension; In Vitro; Infusion procedures; Investigation; Ischemia; Kidney Diseases; Kidney Failure; Limb structure; Literature; Marketing; Measures; Membrane; Mesenchymal; Mesenchymal Stem Cells; Methods; Modeling; Molecular Mechanisms of Action; Multiple Sclerosis; Myocardial Infarction; Nature; Nausea; Neurologic; Organism; Outcome; Parkinson Disease; Pathway interactions; Patient Care; Patients; Phase; Phase III Clinical Trials; Preservation Technique; Process; Proteins; Protocols documentation; Quality Control; Reaction; Reagent; Risk; Safety; Site; Sodium Chloride; Solutions; Spinal cord injury; Stabilizing Agents; Stress; Stroke; Stromal Cells; Structure; Subcellular structure; Suspension substance; Suspensions; Technology; Temperature; Testing; Toxic effect; Transportation; Tryptophan 2,3 Dioxygenase; biological systems; cell type; cellular imaging; clinical application; commercial application; graft vs host disease; high throughput technology; improved; molecular dynamics; nervous system disorder; new technology; polyol; protocol development; public health relevance; research study; respiratory; response; screening; small molecule; solute; stem; sugar

DESCRIPTION (provided by applicant): Cell therapy products is > $1 billion market with aggressive annual growth rates (15- 20%). Of all of the cells therapies currently in development, mesenchymal stem cells (MSCs) appear to have the greatest diversity of applications and potential for widespread use. Mesenchymal stem/stromal cells (MSCs) are being investigated for a variety of applications. Currently, over 200 clinical trials involve the use of MSCs and over 2000 patients have been safely treated with MSCs. MSCs are being investigated for treatment of cardiovascular disorders (stroke, myocardial infarction), diabetes, connective tissue disorders (cartilage defects, osteonecrosis, limb ischemia), chronic obstructive pulmonary disease, nervous system disorders (multiple sclerosis, Parkinson Disease, spinal cord injury), kidney diseases and more. Current methods for the preservation of MSCs are suboptimal. Improper methods of preservation are felt to have contributed to a recent failure of a Phase III clinical tral. In addition, the infusion of DMSO-containing cells is associated with adverse events that have been well documented in the clinical literature. Clinical and commercial application of MSCs will require the development of protocols that produce a consistent number of viable and functional cells. The proposed investigation transforms not only the preservation protocol for MSCs but creates a new paradigm by which preservation protocols for other cell types can be developed. We propose to use synergy between multiple preservation compounds to improve preservation outcome and replace conventional toxic cryoprotective agents such as DMSO. Testing solutions using multiple compounds would normally require thousands of experiments. We accelerate the convergence of the studies using a computational algorithm. Finally, we will use molecular dynamics to understand molecular mechanisms of action and rationally select compounds appropriate for testing. This type of approach will be applied first of all to MSCs but can be extended to a variety of different cell types used therapeutically. !

描述（由申请人提供）：细胞治疗产品的市场价值 > 10 亿美元，年增长率极快 (15-20%)。在目前正在开发的所有细胞疗法中，间充质干细胞（MSC）似乎具有最大的应用多样性和广泛使用的潜力。间充质干/基质细胞 (MSC) 正在研究其多种应用。目前，已有 200 多项临床试验涉及 MSC 的使用 2000 名患者已接受 MSC 安全治疗。 MSC 正在研究用于治疗心血管疾病（中风、心肌梗死）、糖尿病、结缔组织疾病（软骨缺损、骨坏死、肢体缺血）、慢性阻塞性肺病、神经系统疾病（多发性硬化症、帕金森病、脊髓损伤）、肾脏疾病等。目前保存 MSC 的方法并不理想。人们认为，保存方法不当是导致最近 III 期临床试验失败的原因之一。此外，输注含 DMSO 的细胞与不良事件相关，这些不良事件已在临床文献中得到充分记录。间充质干细胞的临床和商业应用需要开发能够产生一致数量的活细胞和功能细胞的方案。拟议的研究不仅改变了 MSC 的保存方案，而且创建了一个新的范式，通过该范式可以开发其他细胞类型的保存方案。我们建议利用多种保存化合物之间的协同作用来改善保存效果并取代传统的有毒冷冻保护剂（如 DMSO）。使用多种化合物测试解决方案通常需要数千次实验。我们使用计算算法加速研究的收敛。最后，我们将利用分子动力学来了解分子作用机制并合理选择适合测试的化合物。这种类型的方法将首先应用于间充质干细胞，但可以扩展到治疗中使用的各种不同的细胞类型。 ！