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Stem cell paracrine actions in tissue regeneration and potential therapeutic effect in human endometrium: a retrospective study
Author(s) -
MiguelGómez L,
Ferrero H,
LópezMartínez S,
Campo H,
LópezPérez N,
Faus A,
Hervás D,
Santamaría X,
Pellicer A,
Cervelló I
Publication year - 2020
Publication title -
bjog: an international journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.157
H-Index - 164
eISSN - 1471-0528
pISSN - 1470-0328
DOI - 10.1111/1471-0528.16078
Subject(s) - paracrine signalling , angiogenesis , angiogenin , endometrium , immunohistochemistry , regeneration (biology) , stem cell , biology , medicine , andrology , cancer research , microbiology and biotechnology , receptor
Objective Determining genetic and paracrine mechanisms behind endometrial regeneration in Asherman's syndrome and endometrial atrophy (AS/EA) patients after autologous CD133 + bone marrow‐derived stem cell (CD133 + BMDSC) transplantation. Design Retrospective study using human endometrial biopsies and mouse models. Setting Fundación‐IVI, IIS‐La Fe, Valencia, Spain. Samples Endometrial biopsies collected before and after CD133 + BMDSC therapy, from eight women with AS/EA (NCT02144987) from the uterus of five mice with only left horns receiving CD133 + BMDSC therapy. Methods In human samples, haematoxylin and eosin (H&E) staining, RNA arrays, PCR validation, and neutrophil elastase (NE) immunohistochemistry (IHQ). In mouse samples, PCR validation and protein immunoarrays. Main outcome measures H&E microscopic evaluation, RNA expression levels, PCR, and growth/angiogenic factors quantification, NE IHQ signal. Results Treatment improved endometrial morphology and thickness for all patients. In human samples, Jun , Serpine1, and Il4 were up‐regulated whereas Ccnd1 and Cxcl8 were down‐regulated after treatment. The significant decrease of NE signal corroborated Cxcl8 expression. Animal model analysis confirmed human results and revealed a higher expression of pro‐angiogenic cytokines (IL18, HGF, MCP‐1, MIP2) in treated uterine horns. Conclusions CD133 + BMDSC seems to activate several factors through a paracrine mechanism to help tissue regeneration, modifying endometrial behaviour through an immunomodulatory milieu that precedes proliferation and angiogenic processes. Insight into these processes could bring us one step closer to a non‐invasive treatment for AS/EA patients. Tweetable abstract CD133 + BMDSC therapy regenerates endometrium, modifying the immunological milieu that precedes proliferation and angiogenesis.