title: Paracrine anti-fibrotic effects of neonatal cells and living cell constructs on young and senescent human dermal fibroblasts.
abstract: Senescent cells observed in the area of chronic wounds have been proposed to affect wound healing. Therapeutic approaches against chronic wounds include, among others, the local application of living cell constructs (LCCs), containing fibroblasts and/or keratinocytes. Accordingly, the aim of the present work was to examine the effects of factors secreted by early passage neonatal fibroblasts and LCCs--in the form of a conditioned medium (CM)--on senescent adult dermal fibroblasts regarding functions related to the healing process, i.e., cell proliferation, alpha-smooth muscle actin and metalloproteinase expression, and collagen synthesis. Target cells were fibroblasts senescent either due to subsequent divisions (replicative senescence) or due to an exogenous stress (stress-induced premature senescence). No effect on the proliferation of senescent fibroblasts was observed, as expected. All CMs were found to inhibit overall collagen synthesis both in early passage and in senescent fibroblasts. The LCC-derived CM was found to be more potent than fibroblast-derived CMs and, furthermore, to inhibit alpha-smooth muscle actin expression. In conclusion, these results may indicate anti-contractile and anti-fibrotic activities of factor(s) secreted by neonatal skin fibroblasts, and more intensely by LCCs on adult donor-derived fibroblasts. These activities seem to persist during senescence of the target cells.
authors.affiliation: Laboratory of Cell Proliferation and Aging, Institute of Biology, NCSR "Demokritos,", Athens, Greece.
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Andreas
authors.initials: A
authors.lastname: Armatas
authors.forename: Anastasia
authors.initials: A
authors.lastname: Dimozi
authors.forename: Maria
authors.initials: M
authors.lastname: Lefaki
authors.forename: Pantelis
authors.initials: P
authors.lastname: Vassiliu
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D003094:Collagen / Q000096:biosynthesis*; D017077:Culture Media, Conditioned; D005109:Extracellular Matrix; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D019899:Paracrine Communication; D012867:Skin / Q000378:metabolism*; D017768:Skin, Artificial; D023822:Tissue Engineering; D014945:Wound Healing; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D003094:Collagen; D020781:Matrix Metalloproteinase 1