Mesenchymal cells in surgical wound healing

间充质细胞在手术伤口愈合中的作用

• 批准号: 7060005
• 负责人: NICOLE SIMONE GIBRAN
• 金额: $ 28.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060005
• 关键词: CD antigens; bone marrow; cell differentiation; collagen; diabetes mellitus; disease /disorder model; fibroblasts; genetically modified animals; hematopoietic stem cells; keratinocyte; laboratory mouse; mesenchyme; model design /development; phenotype; postoperative state; protein isoforms; stem cells; tissue /cell culture; transforming growth factors; wound healing

DESCRIPTION (provided by applicant): Following tissue injury, cells are mobilized from the bone marrow to the site of injury. As the inflammatory response subsides, the wound is remodeled to form stratified epithelia over a collagen-rich matrix containing mesenchymal cell types. Although the bone marrow contribution to the inflammatory response is well established, the long-term fate and role of bone marrow-derived cells in a healed cutaneous wound remains less clear. The bone marrow harbors stem cells capable of differentiating along hematopoietic cell and mesenchymal cell lineages. Both stem cell types have a high-degree of plasticity and are capable of contributing cells to multiple tissues, including skin. To better understand the role that bone marrow cells play in wound repair, we developed a chimeric mouse wound model in which mesenchymal stem cells (MSC) from EGFP transgenic mice are transplanted into marrow-ablated C57BL mice. In this grant, we explore the hypothesis that bone marrow-derived mesenchymal stem cells are a critical source of CD45- cells that regulate TGFbeta and collagen production in the skin and wound. We will test our hypothesis with the following specific aims: 1. To determine the cellular phenotype and differentiation capability of bone marrow-derived MSC in normal and wounded murine skin. 2. To determine the effect of MSCs on the production of TGF-Beta isoforms, collagen type I, and collagen type by keratinocytes and fibroblasts. 3. To determine whether bone marrow-derived MSC can reverse diabetes impaired wound healing. 4. To determine whether bone marrow-derived MSC are critical for wound healing.

描述（由申请人提供）： 组织损伤后，将细胞从骨髓动员到损伤部位。随着炎症反应的减退，将伤口重塑以形成分层上皮，这在含有间充质细胞类型的胶原蛋白富基质上。尽管骨髓对炎症反应的贡献已经很好地确定，但骨髓衍生细胞在愈合的皮肤伤口中的长期命运和作用仍然不太清楚。骨髓藏有能够沿造血细胞和间充质细胞谱系区分的干细胞。两种干细胞类型都具有高度的可塑性，并且能够为包括皮肤在内的多个组织贡献细胞。为了更好地理解骨髓细胞在伤口修复中起作用的作用，我们开发了一种嵌合小鼠伤口模型，其中将来自EGFP转基因小鼠的间充质干细胞（MSC）移植到骨髓燃烧的C57BL小鼠中。在这笔赠款中，我们探讨了以下假设：骨髓衍生的间充质干细胞是调节皮肤和伤口中TGFBETA和胶原蛋白产生的CD45细胞的关键来源。我们将以以下特定目的检验我们的假设： 1。确定正常和受伤的鼠皮肤中骨髓衍生的MSC的细胞表型和分化能力。 2。确定MSC对角质形成细胞和成纤维细胞的TGF-β同工型，I型和胶原蛋白类型的影响。 3。确定骨髓来源的MSC是否会逆转糖尿病受损伤口愈合。 4。确定骨髓来源的MSC是否对于伤口愈合至关重要。