Mechanical Activation of Adipose-Derived Stem Cells for the Treatment of Diabetic Foot Ulcers Using a Novel CD-Microfluidic Device

项目总结/摘要 糖尿病足溃疡是非创伤性下肢截肢的主要原因， 到2035年，它有可能严重影响1.48亿人的生活。当前 护理标准包括物理卸载和手术清创，而更新的基于同种异体细胞的 这些治疗方法成本高，结果不可预测。新的研究发现， 脂肪来源的自体干细胞作为一种有效的治疗方法， 生活方式限制条件。 在这里，我们提出了一个即时的封闭系统设备，创建一个'最低限度地操纵' 然后可以将其重新注射回患者体内以治疗这种疾病 生活方式衰弱的并发症，都在几分钟内。我们的设备结合了一种新颖的 离心平台和独特的微流体通道设计， 在脂肪组织中发现的细胞群。这种剪应力激活的概念特别重要 在糖尿病的情况下，由于糖尿病脂肪来源的干细胞表现出大大减少的 与健康的脂肪组织相比，此外，我们的设备具有巨大的潜力， 对于一种精确的医学方法来创造自体疗法，因为剪切应力的量 由我们的装置施加的剂量依赖性增加导致各种干细胞标志物和亚群。 有了这笔资金，我们将优化我们设备的参数，以产生一种治疗方法， 丰富和激活对糖尿病伤口愈合至关重要的脂肪源性干细胞群。一旦我们 确定产生再生种群比例最高的剪切应力， 为了最大限度地提高这种组织的安全性，我们将在各种培养条件下测试干细胞， 展示了伤口愈合的机制。随后，我们将对此进行研究 在动物模型中优化治疗，以证明这种富集/活化的 与来自相同来源的未经处理的脂肪组织相比，这项研究将产生 足够的体外和体内证据，应该推动我们进行II期研究，我们将进一步 在各种临床模型中评价我们的器械产生的治疗剂的安全性和有效性， 糖尿病 我们的多学科团队包括外科医生，生物医学工程师，业务主管和 监管专家，这将大大增加成功的产品，坚持的可能性， 食品和药物管理局支持的最高科学、临床和商业标准。

Project Summary/Abstract The diabetic foot ulcer is the leading cause of nontraumatic lower limb amputations and carries the potential to dramatically affect the lives of 148 million individuals by the year 2035. The current standard of care includes physical offloading and surgical debridement, while newer allogeneic cell-based therapies are riddled with high costs and unpredictable outcomes. Emerging research has identified adipose-derived autologous stem cells as a potent therapeutic for safe and effective treatment of this lifestyle-limiting condition. Here, we propose a point-of-care closed system device that creates a ‘minimally manipulated’ adipose tissue therapeutic that can then be reinjected back into the patient for the treatment of this lifestyle-debilitating complication, all in a matter of minutes. Our device incorporates a novel centrifugation platform and a unique microfluidic channel design that shears and stimulates inherent stem cell populations found in adipose tissue. This concept of shear-stress activation is of particular importance in the setting of diabetes due to the fact that diabetic adipose-derived stem cells exhibit greatly reduced function when compared to healthy adipose tissue. Additionally, our device carries significant potential for a precision medicine approach to creating autologous therapeutics, in that the amount of shear-stress applied by our device leads to dose-dependent increase in various stem cell markers and subpopulations. With this grant we will optimize the parameters of our device to generate a therapeutic that enriches and activates adipose-derived stem cell populations critical to diabetic wound healing. Once we identify the shear-stress that generates the highest proportion of regenerative populations while maximizing the safety profile of this tissue, we will test the stem cells in various culture conditions to demonstrate the mechanisms by which wound healing take place. Subsequently, we will examine this optimized therapeutic in an animal model to demonstrate the superiority of this enriched/activated therapeutic when compared to unprocessed adipose tissue from the same source. This study will generate sufficient in vitro and in vivo evidence that should propel us to a phase II study where we will further evaluate the safety and efficacy of the therapeutic generated by our device in various clinical models of diabetes. Our multidisciplinary team includes surgeons, biomedical engineers, business executives and regulatory experts that will significantly increase the likelihood of a successful product that adheres to the highest scientific, clinical and business standards upheld by the Food and Drug Administration.