期刊
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
卷 127, 期 5, 页码 551-560出版社
WILEY
DOI: 10.1111/1471-0528.16078
关键词
Asherman's syndrome; bone marrow-derived stem cells; endometrial atrophy; endometrial regeneration; paracrine mechanisms
资金
- Instituto de Salud Carlos III, ISCIII [PI17/01039, CD15/00057]
- Generalitat Valenciana [PROMETEO/2018/137, ACIF/2017/118, ACIF/2015/271]
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 Fundacion-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.
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