In situ repair abilities of human umbilical cord–derived mesenchymal stem cells and autocrosslinked hyaluronic acid gel complex in rhesus monkeys with intrauterine adhesion

Abstract

Increasing occurrence of moderate to severe intrauterine adhesion (IUA) is seriously affecting the quality of human life. The aim of the study was to establish IUA models in nonhuman primates and to explore the dual repair effects of human umbilical cord–derived mesenchymal stem cells (huMSCs) loaded on autocrosslinked hyaluronic acid gel (HA-GEL) on endometrial damage and adhesion. Here, we recorded the menstrual cycle data in detail with uterine cavities observed and endometrial tissues detected after intervention, and the thicker endometria, decreased amount of fibrotic formation, increased number of endometrium glands, etc., suggested that both HA-GEL and huMSC/HA-GEL complexes could partially repair IUA caused by mechanical injury, but huMSC/HA-GEL complex transplantation had notable dual repair effects: a reliable antiadhesion property and the promotion of endometrial regeneration.

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Activate PTEN/AKT Pathway and Promote Repair of Damaged Endometrium

“…Cell therapy has been suggested as a new strategy to repair tissue injury. The therapeutic effects of MSC on damaged endometrium have been veri ed in animal models [9][10][11]23]. However, there are some adverse reactions to the application of MSC [12][13][14].…”

Endometrial Perivascular Progenitor Cells and Uterus Regeneration

“…Bone marrow MSCs loading on collagen scaffolds have been reported for application to damaged uterine tissues, which partially differentiated into cells that positively stain for desmin and vimentin, which are known markers of stromal cells, and the expression of growth factors (bFGF, IGF-1, TGF-β1, and VEGF) was detected within two weeks after transplantation, indicating both direct differentiation and secretory effect of MSCs [95]. In addition, an auto-crosslinked hyaluronic acid gel loaded with umbilical cord MSCs in AS rhesus monkey models was found to help uterine regeneration by preventing adhesion as a physical barrier and providing an attachment site for MSCs [96]. Moreover, three-dimensional (3D) printed hydrogels are another biomaterial in AS treatment, providing a spatial and physiological environment for MSC planting [97].…”

Therapeutic Potential of HUMSCs in Female Reproductive Aging

“…For example, in a rat uterine scar model, the application of a scaffold/HUMSCs system both promotes collagen degradation in the uterine scar through the paracrine effect of stem cells and also allows for longer local retention of HUMSCs with longer duration of action ( Xu et al, 2017 ). Recently, Wang et al applied the HUMSCs/HA-GEL system for dual repair of endometrial damage and adhesions in a non-human primate model of uterine adhesions, with the intervention of new materials allowing the maximum effect of HUMSCs ( Wang et al, 2020a ). Considering these existing studies, a new breakthrough in intra-ovarian cell transplantation therapy may be possible through the exploration of combined vector transplantation.…”