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，细胞从骨髓动员到损伤部位。当炎症反应消退时，伤口重塑以在含有间充质细胞类型的富含胶原的基质上形成分层上皮。虽然骨髓对炎症反应的贡献已经得到了很好的证实，但骨髓源性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。骨髓含有能够沿着造血细胞和间充质细胞谱系分化的干细胞。这两种干细胞类型都具有高度的可塑性，能够为多种组织（包括皮肤）提供细胞。为了更好地了解骨髓细胞在伤口修复中的作用，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）移植到骨髓消融的C57 BL小鼠中。在这项研究中，我们探索了骨髓间充质干细胞是调节皮肤和伤口中TGF β和胶原蛋白产生的CD 45细胞的重要来源的假设。我们将通过以下具体目标来检验我们的假设： 1.目的观察小鼠骨髓间充质干细胞在正常和创伤皮肤中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产生TGF-β亚型、I型胶原和I型胶原的影响。 3.确定骨髓来源的MSC是否可以逆转糖尿病受损的伤口愈合。 4.确定骨髓来源的MSC是否对伤口愈合至关重要。