Templin Christian, Grote Karsten, Schledzewski Kai, Ghadri Jelena-Rima, Schnabel Sabine, Napp Lars Christian, Schieffer Bernhard, Kurzen Hjalmar, Goerdt Sergij, Landmesser Ulf, Koenen Wolfgang, Faulhaber Jörg
Cardiovascular Center, Cardiology, University Hospital Zürich, Zürich, Switzerland.
Exp Dermatol. 2009 May;18(5):445-53. doi: 10.1111/j.1600-0625.2008.00809.x. Epub 2009 Mar 6.
Although dermal wounds are common, treatment remains limited and largely ineffective. Recent studies suggest that therapeutic application of progenitor cells is useful for tissue regeneration.
We here investigated the effects exerted by the recently characterized immortalized haematopoietic progenitor cell line DKmix and their conditioned medium in a murine wound healing model.
Injection of both DKmix cells and their conditioned medium accelerated wound repair between days 3 and 10 compared with PBS-injected control mice (n = 8, P < 0.01 DKmix cells vs control, P < 0.01 conditioned medium vs control at day 6). The treated groups exhibited more CD31(+)-capillaries at day 6 after injury compared with the control group (n = 4, P < 0.01 DKmix cells vs control, P < 0.001 conditioned medium vs control), whereas there was no change in infiltrated CD68(+) macrophages. Conditioned medium of DKmix cells induced tube formation of human endothelial cells in Matrigel assays (n = 4-6, P < 0.05 conditioned medium vs control) as well as migration (n = 4, P < 0.01 conditioned medium vs control) and proliferation of murine 3T3 fibroblasts (n = 5, P < 0.05 conditioned medium vs control). Abundant levels of matrix metalloproteinase -2 and -9 in the supernatants were detected. Protein arrays of the supernatants revealed a strong secretion of cytokines and growth factors, such as monocyte chemoatractant protein-1 and GM-CSF from DKmix cells.
DKmix cells improve skin-substitute wound healing by promoting angiogenesis as well as migration and proliferation of fibroblasts. These data suggest that immortalized haematopoietic progenitor cells significantly improve dermal wound healing by paracrine effects.
尽管皮肤伤口很常见，但治疗方法仍然有限且大多无效。最近的研究表明，祖细胞的治疗应用对组织再生有用。
我们在此研究了最近鉴定的永生化造血祖细胞系DKmix及其条件培养基在小鼠伤口愈合模型中的作用。
与注射PBS的对照小鼠相比，注射DKmix细胞及其条件培养基均在第3天至第10天加速了伤口修复（n = 8，第6天时，DKmix细胞与对照组相比P < 0.01，条件培养基与对照组相比P < 0.01）。与对照组相比，治疗组在损伤后第6天显示出更多的CD31(+)毛细血管（n = 4，DKmix细胞与对照组相比P < 0.01，条件培养基与对照组相比P < 0.001），而浸润的CD68(+)巨噬细胞没有变化。在基质胶试验中，DKmix细胞的条件培养基诱导人内皮细胞形成管腔（n = 4 - 6，条件培养基与对照组相比P < 0.05）以及迁移（n = 4，条件培养基与对照组相比P < 0.01），并促进小鼠3T3成纤维细胞增殖（n = 5，条件培养基与对照组相比P < 0.05）。检测到上清液中基质金属蛋白酶-2和-9水平丰富。上清液的蛋白质阵列显示，DKmix细胞强烈分泌细胞因子和生长因子，如单核细胞趋化蛋白-1和粒细胞-巨噬细胞集落刺激因子。
DKmix细胞通过促进血管生成以及成纤维细胞的迁移和增殖来改善皮肤替代物伤口愈合。这些数据表明，永生化造血祖细胞通过旁分泌作用显著改善皮肤伤口愈合。
