Stem cell mobilization and diabetic skin ulcers

描述（由申请人提供）：在过去的十年中，糖尿病患者下肢神经性溃疡的管理变化不大。治愈率差，截肢风险较高，缺乏客观的治疗方法选择。我们将在接受下肢神经性溃疡治疗的糖尿病患者中开展循环和创面缘血管源性干细胞/祖细胞（SPCs）的多中心临床队列研究。目标是开发简单、定量的方法，为有效的治疗选择提供指导。我们的假设是分析SPCs数量及其生化特征可以预测糖尿病足溃疡是否会愈合。实验方法建立在我们初步的R21项目和最近的出版物中使用的非常高效的框架上。这四个具体目标集中在SPCs及其与评估糖尿病控制和伤口特征的传统方法的关联上。目标如下：(1)确定SPCs的动员/伤口再生和缺氧诱导因子相关过程是否与伤口修复有关；(2)评估伤口护理实践是否与SPCs的动员和SPCs归向伤口有关；(3)确定SPCs的变化是否与愈合有关；(4)评估在愈合的急性活检伤口和足部溃疡之间观察到的SPCs差异是否与代谢状态等临床问题有关。我们将评估几种细胞内蛋白的SPCs数量和含量是否与伤口和疾病相关因素相关，以及这些测量是否可用于预测糖尿病伤口愈合。

DESCRIPTION (provided by applicant): Management of lower extremity neuropathic ulcers in diabetic patients has changed little in the past decade. The healing rate is poor, risk of amputations relatively high, and there is a paucity of objective methods for choosing treatments. We will carry out a multi-center clinical cohort study of circulating and wound margin vasculogenic stem/progenitor cells (SPCs) in diabetic patients undergoing treatment for lower extremity neuropathic ulcers. The goal is to develop simple, quantitative methods that provide guidance on effective treatment choices. Our hypothesis is that an analysis of SPCs number and their biochemical characteristics can predict whether diabetic foot ulcers will heal. The experimental approach is built on the very productive framework used in our preliminary R21 project and recent publication. The four specific aims center on SPCs and their association with traditional methods for assessing diabetic control and wound characteristics. Aims are as follows: (1) Determine whether SPCs mobilization/wound recruitment and hypoxia inducible factor-related processes are associated with wound repair, (2) Assess if wound care practices are associated with SPCs mobilization and SPCs homing to wounds, (3) Determine if variations in SPCs are associated with healing, and (4) Assess whether SPCs differences observed between a healing acute biopsy wound versus the foot ulcer are related to clinical issues such as metabolic status. We will evaluate whether SPCs number and content of several intracellular proteins correlate with wound and disease-related factors and whether these measurements can be used to predict diabetic wound healing.