TABLE 2.
Summary of bioactive hydrogels in cell therapy in IUA.
| Cell | Biomaterial | Model | Molecule/pathway | Strength | References |
|---|---|---|---|---|---|
| - | Chitosan-heparin hydrogels | Sprague-Dawley rats | Downregulated expression of TGF-β | SDF-1α/CXCR4 axle secreted cytokine to regulate the tissue regeneration | Wenbo et al. (2020) |
| Upregulated expression of VEGF | |||||
| - | E2@uECMNPs/AP hydrogel | Sprague-Dawley rats | Upregulated Ki67, cytokeratin, and ER-β | Increased morphological recovery and decreased uterine fibrosis rate | Yao et al. (2020) |
| Decreased TGF-β1 and TNF-α | |||||
| - | E2-Heparin-Poloxamer Hydrogel | Sprague-Dawley rats | Kisspeptin; ERK1/2 and MAPKs p38 pathways | Facilitate the regeneration | Zhang et al. (2020b) |
| Inhibiting the cell apoptosis in IUA model | |||||
| dEMSCs | Hyaluronic acid fibrinogen/thrombin hydrogel (HA + F + T50 gel) | Sprague-Dawley rats | Increased expression of PECAM and IGF-1 | Expression and secretion of molecules essential for embryonic implantation | Kim et al. (2019) |
| VEGF and LIF expression are also increased | Shortens time window between cell transplantation and embryo transfer | ||||
| MSC-Sec | Crosslinked hyaluronic acid gel | Sprague-Dawley rats | - | Creates a sustained release system | Liu et al. (2019) |
| Thicker endometrium and more glands were observed after treatment | |||||
| BMSCs | Pluronic F-127-vitminC hydrogel | Sprague-Dawley rats | Restored cytokeratin, von Willebrand Factor (vWF) | Vc promoted the survival and health of PF-127-encapsulated BMSCs in vitro | Yang et al. (2017) |
| Decreased interleukin-1β (IL-1β) | Thicker endometrium membrane | ||||
| More glands and fewer areas of fibrosis | |||||
| Oral mucosal epithelial cells | Lyophilized amniotic membrane | Sprague-Dawley rats | VEGF expression is increased | Effective in preventing fibrosis with improved regeneration of endometrium and endometrial glands in the rat model of IUA | Chen et al. (2019) |
| OMECs | |||||
| hUCMSC | Collagen | Sprague-Dawley rats | Increased the expression of HuNu and vimentin in a IUA-induced rat model | Increased number of endometrial glands and reduced area of fibrosis | Liu et al. (2020b) |
| Protein levels of the p-transcriptional co-activator with PDZ-binding motif, stromal cell-derived factor-1, and C-X-C chemokine receptor type 4 were upregulated | |||||
| UC-MSCs | Collagen | Human | - | 38.4% participants had a successful pregnancy | Cao et al. (2018) |
| UC-MSC-derived exosomes | Collagen | Sprague-Dawley rats | Increased the expression of the estrogen receptor α/progesterone receptor | Endometrium regeneration | Xin et al. (2020) |
| Collagen remodeling | |||||
| Increased the expression of the estrogen receptor α/progesterone receptor | |||||
| Restored fertility | |||||
| Reduced inflammation, and increased anti-inflammatory responses | |||||
| hiMSCs | Alginate and gelatin | Sprague-Dawley rats | Integrin αv β3 and LIF were significantly higher in the cell-loaded scaffold group | Promoted the recovery of the endometrial histomorphology (endometrial tissue and gland regeneration) and the regeneration of endometrial cells (stromal cells and epithelial cells) and endothelial cells | Ji et al. (2020) |
| Improved endometrial receptivity functional indicators | |||||
| ADSCs-derived exosomes | PEG | Sprague-Dawley rats | Significant increases in VEGF, LIF, avβ3, and IGF-1 expression | Promote HUVEC proliferation, migration, and tube formation in vitro | Pan et al. (2020) |
| Exhibited a robust ability to induce neovascularization and tissue regeneration while suppressing localized fibrosis in vivo | |||||
| Regenerated endometrial tissue was more receptive to embryos, leading to higher rates of pregnancy |
hAECs: human amnion epithelial cells; bFGF: basic fibroblast growth factor; VEGF: vascular endothelial growth factor; IGF-1: insulin-like growth factor-1; COL1A1: collagen type I alpha 1; TIMP-1: tissue inhibitor of metalloproteinase-1; TGF-β: transforming growth factor-β; PDGF-C: platelet-derived growth factor-C; THBS1: thrombospondin-1; CTGF: connective tissue growth factor; ER-β: estrogen receptor β; E2@uECMNPs/AP hydrogel: nanoparticulate decellularized uterus (uECMNPs) encapsulated β-estradiol thermosensitive aloe-poloxamer hydrogel; MenSCs: menstrual blood stem cells; BMSCs: bone marrow-derived stem cells; dEMSCs: decidualized endometrial stromal cells; MSC-Sec: mesenchymal stem cell-secretome; UC-MSCs: umbilical cord-derived mesenchymal stromal cells; ADSCs: adipose stem cells.