Stem cell mobilization and diabetic skin ulcers

干细胞动员和糖尿病皮肤溃疡

基本信息

批准号：
8370929
负责人：
David Margolis
金额：
$ 76.73万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8370929
关键词：
Acute Address Agreement Amputation Animals Area Biochemical Biopsy Blood specimen Caring Cell Count Cell physiology Cells Cellular biology Characteristics Clinic Clinical Clinical Research Clinical Services Cohort Studies Communities Data Debridement Diabetes Mellitus Diabetic Foot Ulcer Disease Distal Documentation Ethics Event Foot Ulcer Goals Healed Hematopoietic Stem Cell Mobilization Homing Hyperbaric Oxygen Hypoxia Inducible Factor Impairment Institutes Institutional Review Boards Intervention Limb structure Lower Extremity Manuals Maryland Measurement Metabolic Methods Neuropathy New York Ohio Patients Persons Pharmaceutical Preparations Population Study Procedures Process Proteins Publications Publishing Recruitment Activity Refractory Remunerations Research Risk Secure Site Skin Ulcer Stem cells Sterile coverings Techniques Tissue Sample Tissues Treatment Protocols Ulcer Variant Work Wound Healing base community based treatment diabetic diabetic patient diabetic wound healing effective therapy genetic regulatory protein healing improved insight neovascularization patient population response standard care stem success tool treatment planning wound

项目摘要

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. PUBLIC HEALTH RELEVANCE: We plan to carry out a multi-center clinical cohort study of circulating and wound margin vasculogenic stem/progenitor cells in diabetic patients undergoing treatment for limb-threatening lower extremity neuropathic ulcers. The goal is to develop simple, quantitative methods to assess ulcers that provide guidance on effective treatment choices. Our hypothesis is that an analysis of stem/progenitor cell number and their biochemical characteristics can predict whether diabetic foot ulcers will heal.

描述（由申请人提供）：糖尿病患者下肢神经性溃疡的治疗在过去十年中几乎没有变化。治愈率较差，截肢风险较高，缺乏客观的治疗选择方法。我们将对接受下肢神经性溃疡治疗的糖尿病患者的循环和伤口边缘血管生成干/祖细胞（SPC）进行多中心临床队列研究。目标是开发简单的定量方法，为有效的治疗选择提供指导。我们的假设是，对 SPC 数量及其生化特征的分析可以预测糖尿病足溃疡是否会愈合。该实验方法建立在我们初步 R21 项目和最近出版物中使用的非常高效的框架之上。这四个具体目标集中在 SPC 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 SPC 动员/伤口募集和缺氧诱导因子相关过程是否与伤口修复相关，(2) 评估伤口护理实践是否与 SPC 动员和 SPC 归巢伤口相关，(3)确定 SPC 的变化是否与愈合相关，并且 (4) 评估在愈合中的急性活检伤口与足部溃疡之间观察到的 SPC 差异是否与代谢状态等临床问题相关。我们将评估 SPC 的数量和几种细胞内蛋白质的含量是否与伤口和疾病相关因素相关，以及这些测量结果是否可用于预测糖尿病伤口愈合。公共健康相关性：我们计划对正在接受威胁肢体的下肢神经性溃疡治疗的糖尿病患者的循环和伤口边缘血管生成干细胞/祖细胞进行多中心临床队列研究。目标是开发简单、定量的方法来评估溃疡，为有效的治疗选择提供指导。我们的假设是，对干细胞/祖细胞数量及其生化特征的分析可以预测糖尿病足溃疡是否会愈合。