Frontiers in Cell and Developmental Biology (Feb 2021)

Scar-Free Healing of Endometrium: Tissue-Specific Program of Stromal Cells and Its Induction by Soluble Factors Produced After Damage

  • Roman Eremichev,
  • Maria Kulebyakina,
  • Nataliya Alexandrushkina,
  • Nataliya Alexandrushkina,
  • Peter Nimiritsky,
  • Peter Nimiritsky,
  • Nataliya Basalova,
  • Nataliya Basalova,
  • Olga Grigorieva,
  • Mane Egiazaryan,
  • Daniyar Dyikanov,
  • Vsevolod Tkachuk,
  • Vsevolod Tkachuk,
  • Vsevolod Tkachuk,
  • Pavel Makarevich,
  • Pavel Makarevich

DOI
https://doi.org/10.3389/fcell.2021.616893
Journal volume & issue
Vol. 9

Abstract

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Besides certain exceptions, healing of most tissues in the human body occurs via formation of scar tissue, rather than restoration of lost structures. After extensive acute injuries, this phenomenon substantially limits the possibility of lost function recovery and, in case of chronic injury, it leads to pathological remodeling of organs affected. Managing outcomes of damaged tissue repair is one of the main objectives of regenerative medicine. The first priority for reaching it is comparative investigation of mechanisms responsible for complete restoration of damaged tissues and mechanisms of scarring. However, human body tissues that undergo complete scar-free healing are scarce. The endometrium is a unique mucous membrane in the human body that heals without scarring after various injuries, as well as during each menstrual cycle (i.e., up to 400 times during a woman’s life). We hypothesized that absence of scarring during endometrial healing may be associated with tissue-specific features of its stromal cells (SCs) or their microenvironment, since SCs transform into myofibroblasts—the main effector link of scarring. We found that during healing of the endometrium, soluble factors are formed that inhibit the transition of SCs into myofibroblasts. Without influence of these factors, the SCs of the endometrium undergo transformation into myofibroblasts after transforming growth factor β1 (TGF-β1) treatment as well as the SCs from tissues that heal by scarring—skin or fat. However, unlike the latter, endometrial SCs organize extracellular matrix (ECM) in a specific way and are not prone to formation of bulky connective tissue structures. Thus, we may suggest that tissue-specific features of endometrial SCs along with effects of soluble factors secreted in utero during menstruation ensure scar-free healing of human endometrium.

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