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: 7394355
• 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/7394355
• 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（由申请人提供）：Susan Volk 博士之前曾在 NIH 资助的 VMD-PhD 项目中接受过基础科学培训，随后完成了作为兽医的亚专业临床培训。该提案为她带来了一个新的研究方向，重点是基于间充质干细胞（MSC）的慢性皮肤伤口治疗以及伤口愈合的分子机制。导师艾伦·弗莱克博士将贡献干细胞治疗领域的专业知识，并指导候选人开发独立的研究项目。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、研究伦理培训和研究生课程。候选人作为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。研究重点是确定局部应用 MSC 治疗缺血性伤口的疗效并剖析其治疗作用的机制。缺血性伤口带来了巨大的临床挑战，导致住院时间延长和医疗费用高昂。迄今为止，缺乏针对缺血性溃疡和其他慢性不愈合伤口的有效疗法。该提案中的证据表明，骨髓来源的间充质干细胞可以改善缺血性伤口的愈合。待检验的假设是间充质干细胞通过直接和间接机制改善缺血性伤口愈合。 Aim1 将评估 MSC 通过促进收缩、上皮化和肉芽组织形成来显着提高缺血性伤口愈合速度的能力。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进行表征的小鼠模型。目标 2 将检验以下假设：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。预计这些研究可能会导致治疗缺血性伤口的组织工程方法；使用离体扩增的 MSC，还为对于治愈缺血组织至关重要的分子机制提供了重要的新见解。这种培训和研究的结合将使候选人能够转变为完全独立的研究人员，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。