Medina Abelardo, Kilani Ruhangiz T, Carr Nicholas, Brown Erin, Ghahary Aziz
British Columbia Professional Fire Fighters' Burn/Wound Healing Laboratory, University of British Columbia, Vancouver, British Columbia, Canada.
Am J Pathol. 2007 Oct;171(4):1140-52. doi: 10.2353/ajpath.2007.070051. Epub 2007 Aug 23.
Bone marrow-derived stem cells have the potential to transdifferentiate into unexpected peripheral cells. We hypothesize that circulating bone marrow-derived stem cells might have the capacity to transdifferentiate into epithelial-like cells and release matrix metalloproteinase-1-modulating factors such as 14-3-3varsigma for dermal fibroblasts. We have characterized a subset of peripheral blood mononuclear cells (PBMCs) that develops an epithelial-like profile. Our findings show that these cells develop epithelial-like morphology and express 14-3-3varsigma and keratin-5, -8 as early as day 7 and day 21, respectively. When compared with control, conditioned media collected from PBMCs in advanced epithelial-like differentiation (cultures on days 28, 35, and 42) increased the matrix metalloproteinase-1 expression in dermal fibroblasts (P </= 0.01). The depletion of 14-3-3varsigma from these conditioned media by immunoprecipitation reduced the effect by 39.5% (P value, 0.05). Therefore, the releasable 14-3-3varsigma from PBMC-derived epithelial-like cells is involved in this process. Our findings provide new insights into the PBMC transdifferentiation to generate epithelial-like cells and subsequently release of 14-3-3varsigma that will disclose new therapeutic alternatives for different dermal clinical settings.
骨髓来源的干细胞具有转分化为意想不到的外周细胞的潜力。我们假设循环中的骨髓来源干细胞可能具有转分化为上皮样细胞的能力,并释放基质金属蛋白酶-1调节因子,如14-3-3varsigma,作用于真皮成纤维细胞。我们已经鉴定出一群具有上皮样特征的外周血单核细胞(PBMC)。我们的研究结果表明,这些细胞早在第7天和第21天分别呈现上皮样形态,并表达14-3-3varsigma和角蛋白-5、-8。与对照组相比,从处于上皮样分化晚期(培养28、35和42天)的PBMC收集的条件培养基增加了真皮成纤维细胞中基质金属蛋白酶-1的表达(P≤0.01)。通过免疫沉淀从这些条件培养基中去除14-3-3varsigma可使该效应降低39.5%(P值,0.05)。因此,PBMC来源的上皮样细胞释放的14-3-3varsigma参与了这一过程。我们的研究结果为PBMC转分化产生上皮样细胞并随后释放14-3-3varsigma提供了新的见解,这将为不同的皮肤临床情况揭示新的治疗选择。