Development of effective in-office autologouscell therapy for osteoarthritis

项目摘要 骨关节炎是当今世界卫生系统面临的一个重大挑战， 退行性关节疾病和老年人慢性残疾的主要原因。仅在美国，OA 影响到3 000万人，造成3 030亿美元的经济负担。可用的药物治疗 仅提供症状性疼痛缓解，且不能阻止与 OA。通过植入人工关节结构来促进软骨修复的外科手术费用昂贵 需要长期康复并可能使患者面临并发症风险的手术。 JointechLabs（JTL）提出了一种创新的OA再生协议，可以很容易地 POC（Point Of Care）。JTL方法OA结合了第一次再生愈合 干细胞的特性和长期粘性补充的益处。所提出的创新在于 JTL开发的两个组件的独特组合：1）独特的便携式和一次性封闭式 用于在非受控环境中制备和收获自体脂肪源性干细胞（ADSC）的系统 2）第一个临床批准的粘性补充剂产品，可以作为支架支撑茎 细胞生长这种组合将允许在床边分离的自体ADSC的关节注射， 封装在一个保护性的水凝胶，这将支持和加速释放再生细胞， 促进OA关节愈合的因素。同时，专利凝胶将提供润滑缓解疼痛， 为一般治疗效果创造有利的环境。 本SBIR第一阶段提案的目标是证明所提议的方法作为一种新的 治疗OA。我们提出了以下具体目标：1）确定最有利的组合， 水凝胶载体和ADSC浓度以支持高再生潜力。2)再生验证 方案使用发炎的人关节的体外模型。与此同时，作用机制的证据 将在分子水平上收集，以在进入临床研究之前获得准确的信息。 SBIR第一阶段项目的成功完成将为第二阶段SBIR提案奠定基础， 将致力于支持IND申请的关键技术产品开发，这将为首次申请开辟道路。 人类临床研究，以验证OA治疗的安全性和有效性。

PROJECT SUMMARY Osteoarthritis is today a major worldwide challenge for health systems, representing the most common degenerative joint disorder and the leading cause of chronic disability among older adults. In the U.S. alone, OA affects 30 million people and it represents a $303 billion economic burden. Available pharmacological treatments only provide symptomatic pain relief and fail to arrest the progressive degeneration of cartilage associated with OA. Surgical procedures that promote cartilage repair by implantation of artificial joint structures are expensive procedures that require long rehabilitation and might expose patients to the risk of complications. JointechLabs (JTL) proposes an innovative regenerative protocol for OA that could be easily implemented at POC (Point Of Care). JTL approach to OA combines for the first time the regenerative healing properties of stem cells and the benefits of long-lasting viscosupplementation. The innovation proposed resides on the unique combination of two components developed by JTL: 1) A unique portable and disposable closed system for the preparation and harvest of Autologous Adipose-Derived Stem Cells (ADSCs) in non-controlled environments; 2) The first clinically approved viscosupplement product that can act as a scaffold to support stem cells growth. This combination will allow the articular injection of Autologous ADSCs isolated at the bedside and encapsulated in a protective hydrogel, which will support and accelerate the release of regenerative cellular factors to promote joint healing in OA. At the same time, the proprietary gel will provide lubrication for pain relief, creating a favorable environment for general therapeutic effect. The goal of this SBIR Phase I proposal is to demonstrate the feasibility of the proposed approach as a new treatment of OA. We propose the following specific aims: 1) Identification of the most favorable combination of hydrogel carrier and ADSCs concentrations to support high regenerative potential. 2) Validation of regenerative protocol using an in vitro model of inflamed human joints. At the same time, evidence of the mechanism of action will be collected at the molecular level to gain accurate information before moving forward into clinical studies. The successful completion of this SBIR Phase I project will lay the foundation of a Phase II SBIR proposal that will address key technical product developments in support of IND application that will open the way to a first-in- human clinical study to validate safety and efficacy of the treatment for OA.