Technology platform for development of multi-component preservation solution

描述（由申请人提供）：细胞治疗产品是> 10亿美元的市场，年增长率（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。间充质干细胞/基质细胞（MSC）正在被研究用于各种应用。目前，超过200项临床试验涉及使用MSC， 2000例患者已安全接受MSC治疗。正在研究MSC用于治疗心血管疾病（中风、心肌梗死）、糖尿病、结缔组织疾病（软骨缺陷、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、帕金森病、脊髓损伤）、肾病等。目前用于保存MSC的方法是次优的。不适当的保存方法被认为是导致最近III期临床试验失败的原因。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。MSC的临床和商业应用将需要开发产生一致数量的活细胞和功能细胞的方案。拟议的调查不仅改变了MSC的保存协议，但创建了一个新的范例，可以开发其他细胞类型的保存协议。我们建议使用多种保存化合物之间的协同作用，以改善保存结果，并取代传统的有毒冷冻保护剂，如DMSO。使用多种化合物测试溶液通常需要数千次实验。我们加速收敛的研究使用的计算算法。最后，我们将使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MSC，但可以扩展到治疗上使用的各种不同的细胞类型。!

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. !