Mesenchymal cells in surgical 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。随着炎症反应的消退，伤口被重塑，在含有间充质细胞类型的富含胶原蛋白的基质上形成复层上皮。尽管骨髓在炎症反应中的作用已经得到了很好的证实，但骨髓来源的细胞在愈合的皮肤伤口中的长期命运和作用仍不清楚。骨髓中含有能够沿着造血细胞和间充质细胞分化的干细胞。这两种干细胞都具有高度的可塑性，能够为包括皮肤在内的多种组织贡献细胞。为了更好地了解骨髓细胞在创伤修复中的作用，我们建立了一种嵌合小鼠创伤模型，将来自绿色荧光蛋白转基因小鼠的间充质干细胞(MSC)移植到骨髓切除的C57BL小鼠中。在这项资助中，我们探索了一种假设，即骨髓来源的间充质干细胞是CD45细胞的关键来源，CD45细胞调节皮肤和伤口中转化生长因子β和胶原的产生。我们将通过以下具体目标来验证我们的假设： 1.测定正常和创伤小鼠皮肤中骨髓间充质干细胞的细胞表型和分化能力。 2.检测骨髓间充质干细胞对角质形成细胞和成纤维细胞分泌转化生长因子-β亚型、I型胶原和I型胶原的影响。 3.确定骨髓间充质干细胞能否逆转糖尿病损伤的创面愈合。 4.确定骨髓间充质干细胞对创面愈合是否起关键作用。

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.