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Transdifferentiation of peripheral blood mononuclear cells into epithelial-like cells.

The American journal of pathology (2007-08-25)
Abelardo Medina, Ruhangiz T Kilani, Nicholas Carr, Erin Brown, Aziz Ghahary
ZUSAMMENFASSUNG

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.

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Anti-Tumor Necrosis Factor-α Antibody, clone 2C8, clone 2C8, Chemicon®, from mouse