Mesenchymal Stem Cell Application for Ischemic wound Healing

间充质干细胞在缺血性伤口愈合中的应用

• 批准号: 7260267
• 负责人: SUSAN W VOLK
• 金额: $ 12.76万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-10 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7260267
• 关键词: Address; Animals; Basic Science; Biological Assay; Biology; Blood Vessels; Bone Marrow; Cell Therapy; Cells; Chronic; Clinical; Collagen; Collagen Type III; Communities; Complement; Conditioned Culture Media; Connective Tissue; Contracts; Cutaneous; Data; Doctor of Philosophy; Ear; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Equilibrium; Etiology; Expenditure; Extracellular Matrix; Genetic; Granulation Tissue; Growth Factor; Harvest; Healed; Healthcare; Hospitalization; Immunoblotting; Immunohistochemistry; Impaired wound healing; Impairment; Inflammatory; Investigation; Ischemia; Knockout Mice; Lead; Mediator of activation protein; Mentors; Mesenchymal Stem Cells; Modeling; Molecular; Mus; Myofibroblast; Oryctolagus cuniculus; Phenotype; Play; Population; Process; Production; Rate; Research; Research Ethics; Research Personnel; Research Training; Rho-associated kinase; Role; Small Interfering RNA; Stem cells; Surgeon; Testing; Therapeutic Effect; Tissue Engineering; Tissues; Topical application; Training; Transplantation; Ulcer; Wild Type Mouse; Work; Wound Healing; angiogenesis; base; cell growth; healing; improved; in vivo; insight; keratinocyte; migration; neovascularization; paracrine; programs; protein expression; repaired; response; soft tissue; stem cell therapy; wound

DESCRIPTION (provided by applicant): Dr. Susan Volk has previous basic science training in an NIH-sponsored VMD-PhD program and subsequently completed subspecialty clinical training as a veterinary surgeon. This proposal involves a new research direction for her, focusing on mesenchymal stem cell (MSC) based therapy for chronic cutaneous wounds and the molecular mechanisms of wound healing. The mentor, Dr. Alan Flake, will contribute expertise in the field of stem cell therapies and guide the candidate in developing an independent research program. Additional contributors will provide expertise in the fields of wound healing, dermatopathology and extracellular matrix biology. The academic component will include seminars, training in research ethics, and graduate-level courses. The candidate's limited clinical activities as a small animal soft tissue surgeon will complement her basic science investigation. Research will focus on establishing vulnerary efficacy of topically applied MSC to treat ischemic wounds and dissecting mechanisms of their therapeutic effects. Ischemic wounds create a formidable clinical challenge, with prolonged hospitalization and substantial healthcare expenditure. To date, effective therapies for ischemic ulcers and other chronic nonhealing wounds are lacking. Evidence in this proposal suggests that bone marrow derived MSC improve healing of ischemic wounds. The hypothesis to be tested is that MSC improve ischemic wound healing by both direct and indirect mechanisms. Aim1 will evaluate the capacity of MSC to significantly improve the rate at which ischemic wounds heal by promoting contraction, epithelialization and granulation tissue formation. This will be accomplished using two models of ischemic wound healing: an established rabbit ear model and a murine model that will be characterized. Aim 2 will test the hypotheses that MSC contribute directly to the wound healing as a myofibroblast and indirectly by producing paracrine factors that promote angiogenesis and epithelialization. It is anticipated that these studies may lead to tissue engineering approaches for treating ischemic wounds; using ex vivo expanded MSC and also provide substantial new insights into molecular mechanisms that are critical for healing ischemic tissues. This combination of training and research will allow the candidate to transition to a fully independent research investigator making contributions to the field of soft-tissue repair, while also retaining ties to the clinical veterinary community.

描述(由申请者提供)：Susan Volk博士曾在NIH赞助的VMD-PhD项目中接受过基础科学培训，随后作为一名兽医完成了专科临床培训。这项建议为她提供了一个新的研究方向，重点是以间充质干细胞(MSC)为基础的慢性皮肤创伤的治疗和伤口愈合的分子机制。这位导师艾伦·弗莱克博士将贡献干细胞疗法领域的专业知识，并指导候选人制定独立的研究计划。其他贡献者将提供伤口愈合、皮肤病理学和细胞外基质生物学领域的专业知识。学术部分将包括研讨会、研究道德培训和研究生课程。候选人作为一名小动物软组织外科医生的有限临床活动将补充她的基础科学研究。研究重点将集中在确定局部应用MSC治疗缺血性伤口的安全性，并剖析其治疗效果的机制。缺血创面造成了巨大的临床挑战，住院时间长，医疗保健支出大。到目前为止，对于缺血性溃疡和其他慢性不可愈合的伤口缺乏有效的治疗方法。这项建议中的证据表明，骨髓来源的MSC可以促进缺血伤口的愈合。需要验证的假设是，MSC通过直接和间接两种机制促进缺血伤口的愈合。AIM1将评估MSC通过促进收缩、上皮化和肉芽组织形成显著提高缺血创面愈合速度的能力。这将使用两种缺血性伤口愈合模型来完成：已建立的兔耳模型和将被表征的小鼠模型。目的2验证以下假设：MSC作为肌成纤维细胞直接促进伤口愈合，并通过产生促进血管生成和上皮化的旁分泌因子间接促进伤口愈合。预计这些研究可能导致组织工程学方法治疗缺血创面；使用体外扩增的MSC，并为修复缺血组织的关键分子机制提供实质性的新见解。这种培训和研究的结合将使候选人能够过渡到一名完全独立的研究调查员，为软组织修复领域做出贡献，同时也保持与临床兽医界的联系。