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Originally published online as doi:10.2353/ajpath.2007.070051 on August 23, 2007

Published online before print August 23, 2007
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(American Journal of Pathology. 2007;171:1140-1152.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070051

Transdifferentiation of Peripheral Blood Mononuclear Cells into Epithelial-Like Cells

Abelardo Medina*, Ruhangiz T. Kilani*, Nicholas Carr{dagger}, Erin Brown{dagger} and Aziz Ghahary*

From the British Columbia Professional Fire Fighters’ Burn/Wound Healing Laboratory* and the Division of Plastic Surgery,{dagger} University of British Columbia, Vancouver, British Columbia, Canada

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 14-3-3{varsigma} 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 14-3-3{varsigma} 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 14-3-3{varsigma} from these conditioned media by immunoprecipitation reduced the effect by 39.5% (P value, 0.05). Therefore, the releasable 14-3-3{varsigma} 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 14-3-3{varsigma} that will disclose new therapeutic alternatives for different dermal clinical settings.




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