Technology platform for development of multi-component preservation solution

多组分保存解决方案开发技术平台

基本信息

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
项目类别：
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

项目摘要

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）：细胞疗法产品> 10亿美元的市场，年增长率（15-20％）。在目前正在发育的所有细胞疗法中，间充质干细胞（MSC）的应用多样性和广泛使用的潜力最大。正在研究各种应用中，正在研究间充质干/基质细胞（MSC）。目前，超过200项临床试验涉及MSC及以上的使用 2000名患者已安全地接受了MSC治疗。正在研究MSC，以治疗心血管疾病（中风，心肌梗死），糖尿病，结缔组织疾病（软骨缺陷，骨坏死，肢体缺血），慢性阻塞性肺部疾病，神经系统疾病，多发性粘膜疾病，parkinson疾病，帕克森氏病，帕克森氏病，棘手疾病），更多。当前保存MSC的方法是次优的。认为保存的方法不当会导致最近的III期临床TRAL失败。此外，含DMSO的细胞的输注与临床文献中已经有充分记录的不良事件有关。 MSC的临床和商业应用将需要开发产生一致数量可行和功能细胞的方案。拟议的调查不仅改变了MSC的保存方案，还可以创建一个新的范式，可以通过该范式来开发其他细胞类型的保存方案。我们建议在多种保存化合物之间使用协同作用来改善保存结果并替代常规的有毒冷冻保护剂，例如DMSO。使用多种化合物测试溶液通常需要数千个实验。我们使用计算算法加速了研究的收敛性。最后，我们将使用分子动力学来了解适合测试的作用和合理选择化合物的分子机制。这种类型的方法将首先应用于MSC，但可以将其扩展到使用治疗的各种不同细胞类型。呢