Sytina E.V., Chikitkina Y.A., Tenchurin T.Kh., Paltsev M.A., Panteleyev A.A.

Introduction. Contracting deep scars are almost unresponsive to conservative treatment and often require repeated surgical intervention. These scars represent a serious problem in skin therapy after the extensive damage. Just the impairment of processes of the dermis reconstitution results in the failure of healing and leads to the development of cicatricial contractions. Skin in the mammalian fetus (until the certain stage of the development) were previously shown to possess of the ability to heal without scarring, with complete restoration of the original epidermal and dermal structure, thus representing an example of true (epimorphic) regeneration. Investigation of the processes underlying this ability and its loss at the late stages of the antenatal development is of considerable interest, determined the high demand of new therapeutic approaches in the treatment of scar complications. The aim of the study. In order to identify changes in the fibroblast phenotype we assessed the contracting capacity with the use of primary mouse embryonic fibroblasts collected at various stages of the antenatal development (before and after the transition from skin regeneration to healing with scar formation). Results. Our studies demonstrated fibroblasts to show the significant shift in the contractile potential during progression from early (regenerative) to late (healing) stages of the fetal skin development.
embryonic fibroblasts, scarless healing, contractility

Список литературы: 
  1. Yannas I.V. Emerging rules for inducing organ regeneration. Biomaterials. 2013; 34 (2): 321–30.
  2. Hinz B. Formation and function of the myofibroblast during tissue repair. J. Invest Dermatol. 2007; 127 (3): 526–37.
  3. Bainbridge P.J. Wound healing and the role of fibroblasts.Wound Care. 2013; 22 (8): 407–8, 410–12.
  4. Hess A. Reactions of mammalian fetal tissues to injury. Skin Anat Rec. 1954; 119: 435–47.
  5. Colwell A.S., Longaker M.T., Lorenz H.P. Mammalian fetal organ regeneration. Adv. Biochem. Eng Biotechnol. 2005; 93: 83–100.
  6. Kishi K., Okabe K., Shimizu R., Kubota Y. Fetal Skin Possesses the Ability to Regenerate Completely: Complete Regeneration of Skin. Keio J. Med. 2012; 61 (4): 101–8.
  7. Moulin V., Plamondon M. Differential expression of collagen integrin receptor on fetal vs. adult skin fibroblasts: implication in wound contraction during healing. Br. J. Dermatol. 2002; 147 (5): 886–92.
  8. Lorenz H.P., Lin R.Y., Longaker M.T., Whitby D.J., Adzick N.S. The fetal fibroblast: the effector cell of scarless fetal skin repair. Plast. Reconstr Surg. 1995; 96 (6): 1251–9, discussion 1260–1.
  9. Ho S., Marçal H., Foster L.J. Towards scarless wound healing: a comparison of protein expression between human, adult and foetal fibroblasts. Biomed Res Int. 2014; 2014: 676493.
  10. Moulin V., Larochelle S., Langlois C., Thibault I., Lopez-Vallé C.A., Roy M.Normal skin wound and hypertrophic scar myofibroblasts have differential responses to apoptotic inductors. J. Cell Physiol. 2004; 198 (3): 350–8.
  11. Sarkisov D.S., Perov Yu.M. Mikroskopicheskaya tehnika. 544 s. M.: Medicina, 1996; 16–20. [Sarkisov D.S., Perov Yu. M. Microscopic technique. M.: Medicine, 1996; 544 (in Russian)]
  12. Xu J. Preparation, culture, and immortalization of mouse embryonic fibroblasts. Curr. Protoc. Mol. Biol. 2005; Chapter 28: Unit 28.1.
  13. Farrugia B.L., Brown T.D., Upton Z., Hutmacher D.W., Dalton P.D., Dargaville T.R. Dermal fibroblast infiltration of poly (ε-caprolactone) scaffolds fabricated by melt electrospinning in a direct writing mode. Biofabrication. 2013; 5 (2): 025001.
  14. Sytina E.V., Tenchurin T.H., Rudyak S.G., Saprykin V.P., Romanova O.A., Orehov A.S., Vasil`ev A.L., Alekseev A.A., Chvalun S.N., Pal`cev M.A., Panteleev A.A. Sravnitel`naya ocenka biosovmestimyh polimernyh matriksov, poluchennyh putem e`lektroformovaniya, i ih ispol`zovaniedlya sozdaniya ob``emnyh dermal`nyh e`kvivalentov. Molekulyarnayamedicina. 2014; 6: 38–47. [Sytina E.V., Tenchurin T.H., Rudyak S.G., Saprykin V.P., Romanova O.A., Orehov A.S., Vasiliev A.L., Alekseev A.A., Chvalun S.N., Paltsev M.A., Panteleyev A.A. Comparative biocompatibility of nonwoven polymer scaffolds obtained by electrospinning and their use for development of 3D dermal equivalents. Mol. Med. 2014; 6: 38–47 (in Russian)]
  15. Bell E., Ivarsson B., Merrill C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl. Acad. Sci USA. 1979; 76 (3): 1274–8.
  16. Lee Y.S., Wysocki A., Warburton D., Tuan T.L. Wound healing in development. Birth Defects Res C Embryo Today. 2012; 96 (3): 213–22.
  17. Humphrey J.D., Dufresne E.R., Schwartz M.A. Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol. 2014; 12: 802–12.
  18. Deschene K., Céleste C., Boerboom D., Theoret C.L.Hypoxia regulates the expression of extracellular matrix associated proteins in equine dermal fibroblasts via HIF1. J. Dermatol Sci. 2012; 65 (1): 12–8.
  19. Modarressi A., Pietramaggiori G., Godbout C., Vigato E., Pittet B., Hinz B. Hypoxia impairs skin myofibroblast differentiation and function. J. Invest Dermatol. 2010; 30 (12): 2818–27.
  20. Faulknor R.A., Olekson M.A., Nativ N.I., Ghodbane M., Gray A.J., Berthiaume F. Mesenchymal stromal cells reverse hypoxia-mediated suppression of α-smooth muscle actin expression in human dermal fibroblasts. Biochem. Biophys Res Commun. 2015; 458 (1): 8–13.