Scar-Free Healing of Endometrium: Tissue-Specific Program of Stromal Cells and Its Induction by Soluble Factors Produced After Damage
Open Access
- 25 February 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
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.Funding Information
- Russian Science Foundation (19-75-30007, 19-75-00067)
This publication has 39 references indexed in Scilit:
- Menstrual fluid factors facilitate tissue repair: identification and functional action in endometrial and skin repairThe FASEB Journal, 2018
- Characterization of human-like menstruation in the spiny mouse: comparative studies with the human and induced mouse modelHuman Reproduction, 2018
- Resectoscopic Surgery for Polyps and Myomas: A Review of the LiteratureJournal of Minimally Invasive Gynecology, 2017
- Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative MedicineMRS Bulletin, 2010
- The Scar‐in‐a‐Jar: studying potential antifibrotic compounds from the epigenetic to extracellular level in a single wellBritish Journal of Pharmacology, 2009
- Effect of cesarean delivery on the endometriumInternational Journal of Gynecology & Obstetrics, 2009
- PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healingWound Repair and Regeneration, 2008
- VEGF blockade inhibits angiogenesis and reepithelialization of endometriumThe FASEB Journal, 2008
- Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statementCytotherapy, 2006
- Smooth muscle alpha actin and myosin heavy chain expression in the vascular smooth muscle cells surrounding human endometrial arteriolesHuman Reproduction, 1999