Stem cell paracrine actions in tissue regeneration and potential therapeutic effect in human endometrium: a retrospective study

Abstract

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.

Concentrated small extracellular vesicles from menstrual blood-derived stromal cells improve intrauterine adhesion, a pre-clinical study in a rat model

“…[3][4][5] Transplantation of UC-MSCs and BMSCs has demonstrated excellent therapeutic outcomes in IUA models and clinical studies. 18,19 However, UC-MSCs are allogeneic and have ethical limitations, and the invasive retrieval process of BMSCs is associated with an increased risk of pain and infection. In contrast, MenSCs may be more suitable for clinical applications, with the advantages of high cloning efficacy, non-invasive collection, ethical rationale, and immunomodulatory potential.…”

Adult stem cells in endometrial regeneration: Molecular insights and clinical applications

“…And the transplantation group also had a higher pregnancy rate compared with the non‐transplanted group (90% vs. 30%, p = 0.0225) (Alawadhi et al, 2014 ). Similarly, Cervello and collegues reported that human CD133 + BMDSCs, with intrauterine or tail vein injection in a murine model of EA, could engraft around the endometrial vessels and promote endometrial regeneration through paracrine actions (Cervello et al, 2015 ; de Miguel‐Gomez et al, 2020 ). These findings suggest that endometrial cells can be differentiated from donor BM cells, that is, stem cells from non‐endometrial sources can also participate in endometrial tissue regeneration.…”

Regenerative Potential of DPSCs and Revascularization: Direct, Paracrine or Autocrine Effect?

“…Besides, CD133 + BM-MSCs seem 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 Asherman’s syndrome and endometrial atrophy (AS/EA) patients [ 78 ].…”