Stimulation of Skin and Wound Fibroblast Migration by Mesenchymal Stem Cells Derived from Normal Donors and Chronic Wound Patients
Stimulation of Skin and Wound Fibroblast Migration by Mesenchymal Stem Cells Derived from Normal Donors and Chronic Wound Patients
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DOI：
10.5966/sctm.2011-0029
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发表时间：
2012-03-01
影响因子：
6
通讯作者：
Van Badiavas, Evangelos
中科院分区：
文献类型：
--
作者：
Rodriguez-Menocal, Luis;Salgado, Marcela;Van Badiavas, Evangelos
慢性伤口仍然是患者发病的主要原因，也是医疗保健系统的经济负担。然而，改善伤口愈合的新治疗方法需要解决慢性伤口患者中出现的许多全身合并症（例如糖尿病、慢性肾功能衰竭和动脉或静脉功能不全）引起的细胞变化。这些影响可能包括炎症细胞迁移受损、生长因子产生减少和组织重塑不良。骨髓间充质干细胞 (MSC) 的多功能特性，包括分化成各种细胞类型的能力和分泌加速皮肤伤口愈合重要因子的能力，使 MSC 成为组织修复和再生的有前途的试剂。在这项研究中，我们使用了体外划痕测定程序，其中包含来自正常供体和慢性伤口患者的标记的间充质干细胞和成纤维细胞，以表征这些细胞混合时动员的诱导。改良的博伊登室测定也用于检查可溶性因子对成纤维细胞迁移的影响。这些研究表明，间充质干细胞通过以剂量依赖性方式影响真皮成纤维细胞迁移，在皮肤伤口闭合中发挥作用。然而，与来自正常供体的成纤维细胞和间充质干细胞相比，慢性伤口患者的成纤维细胞和间充质干细胞存在缺陷。这些发现为开发专门针对使用骨髓间充质干细胞进行伤口愈合的疗法奠定了基础，并可能有助于深入了解某些伤口不愈合的原因。干细胞转化医学 2012；1:221-229
Chronic wounds continue to be a major cause of morbidity for patients and an economic burden on the health care system. Novel therapeutic approaches to improved wound healing will need, however, to address cellular changes induced by a number of systemic comorbidities seen in chronic wound patients, such as diabetes, chronic renal failure, and arterial or venous insufficiency. These effects likely include impaired inflammatory cell migration, reduced growth factor production, and poor tissue remodeling. The multifunctional properties of bone marrow-derived mesenchymal stem cells (MSCs), including their ability to differentiate into various cell types and capacity to secrete factors important in accelerating healing of cutaneous wounds, have made MSCs a promising agent for tissue repair and regeneration. In this study we have used an in vitro scratch assay procedure incorporating labeled MSCs and fibroblasts derived from normal donors and chronic wound patients in order to characterize the induction of mobilization when these cells are mixed. A modified Boyden chamber assay was also used to examine the effect of soluble factors on fibroblast migration. These studies suggest that MSCs play a role in skin wound closure by affecting dermal fibroblast migration in a dose-dependent manner. Deficiencies were noted, however, in chronic wound patient fibroblasts and MSCs as compared with those derived from normal donors. These findings provide a foundation to develop therapies targeted specifically to the use of bone marrow-derived MSCs in wound healing and may provide insight into why some wounds do not heal. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:221-229