title: Therapeutic potential of gingival fibroblasts for cutaneous radiation syndrome: comparison to bone marrow-mesenchymal stem cell grafts.
abstract: Mesenchymal stem cell (MSC) therapy has recently been investigated as a potential treatment for cutaneous radiation burns. We tested the hypothesis that injection of local gingival fibroblasts (GFs) would promote healing of radiation burn lesions and compared results with those for MSC transplantation. Human clinical- grade GFs or bone marrow-derived MSCs were intradermally injected into mice 21 days after local leg irradiation. Immunostaining and real-time PCR analysis were used to assess the effects of each treatment on extracellular matrix remodeling and inflammation in skin on days 28 and 50 postirradiation. GFs induced the early development of thick, fully regenerated epidermis, skin appendages, and hair follicles, earlier than MSCs did. The acceleration of wound healing by GFs involved rearrangement of the deposited collagen, modification of the Col/MMP/TIMP balance, and modulation of the expression and localization of tenascin-C and of the expression of growth factors (VEGF, EGF, and FGF7). As MSC treatment did, GF injection decreased the irradiation-induced inflammatory response and switched the differentiation of macrophages toward an M2-like phenotype, characterized by CD163(+) macrophage infiltration and strong expression of arginase-1. These findings indicate that GFs are an attractive target for regenerative medicine, for easier to collect, can grow in culture, and promote cutaneous wound healing in irradiation burn lesions.
authors.affiliation: 1 Institut de Radioprotection et de Sûreté Nucléaire (IRSN) , Fontenay-aux-Roses, France .
authors.forename: Christine
authors.initials: C
authors.lastname: Linard
authors.forename: Frederique
authors.initials: F
authors.lastname: Tissedre
authors.forename: Elodie
authors.initials: E
authors.lastname: Busson
authors.forename: Valerie
authors.initials: V
authors.lastname: Holler
authors.forename: Thomas
authors.initials: T
authors.lastname: Leclerc
authors.forename: Carine
authors.initials: C
authors.lastname: Strup-Perrot
authors.forename: Ludovic
authors.initials: L
authors.lastname: Couty
authors.forename: Bruno
authors.initials: B
authors.lastname: L'homme
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Antoine
authors.initials: A
authors.lastname: Lafont
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Lataillade
authors.forename: Bernard
authors.initials: B
authors.lastname: Coulomb
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016513:Mice, SCID; D011832:Radiation Injuries / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000293:injuries / Q000473:pathology*; D014945:Wound Healing / Q000502:physiology*