Sodium alginate-bioglass-encapsulated hAECs restore ovarian function in premature ovarian failure by stimulating angiogenic factor secretion

Abstract

Background Human amniotic epithelial cells (hAECs) exhibit a strong capability to restore ovarian function in chemotherapy-induced premature ovarian failure (POF). However, the therapeutic efficacy of hAECs is usually affected by the limited number and proliferative ability of grafted hAECs in target organs. The transplantation of stem cells encapsulated in sodium alginate-bioglass (SA-BG) composite hydrogel has recently been shown to be an effective strategy for tissue regeneration. The current study aims to investigate the therapeutic potential of hAECs or hAEC-derived conditioned medium (CM) encapsulated in SA-BG in mice with chemotherapy-induced POF. Methods C57BL/6 mice were intraperitoneally injected with chemotherapy drugs to induce POF. hAECs or CM were harvested and encapsulated in SA-BG composite hydrogel, which were transplanted onto the injured ovaries of mice with POF. Follicle development, granulosa cell function, and ovarian angiogenesis were evaluated by morphological methods. To further elucidate the effect of SA-BG-encapsulated hAECs/CM on vascularization, the tube formation of human umbilical vein epithelial cells (hUVECs) was conducted in vitro. Cytokine array and ELISA were used to analyze and quantify the effects of bioactive components released by SA-BG on the secretion of angiogenic factors by hAECs. Results The transplantation of SA-BG-encapsulated hAECs/CM restored follicle development, repaired granulosa cell function, and enhanced ovarian angiogenesis in POF mice. The further study showed that SA-BG significantly promoted the tube formation of hUVECs in vitro. Moreover, encapsulating hAECs could facilitate the effect of SA-BG on inducing the formation of the capillary tube in a paracrine manner. In addition, we found that SA-BG extracts significantly enhanced the viability of hAECs and stimulated the secretion of pro-angiogenic factors of hAECs. Notably, compared with SA-BG/CM, SA-BG/hAECs achieve better therapeutic effects, possibly because stimulation of BG enhanced the viability and paracrine capacity of hAECs. Conclusions The present study initially demonstrates that SA-BG-encapsulated hAECs or CM can exert a therapeutic effect on chemotherapy-induced POF mainly by protecting granulosa cell function and enhancing ovarian vascularization, which might provide a novel strategy for the delivery of hAECs for treating POF.

Mesenchymal stem cells combined with autocrosslinked hyaluronic acid improve mouse ovarian function by activating the PI3K-AKT pathway in a paracrine manner

“…Several strategies have been introduced to improve the effectiveness of MSCs, such as the use of sodium alginate-bioglass composite hydrogels and type I collagen as scaffolds during transplantation [ 9 , 10 ]. However, commercialized products widely accepted in clinical practice are still lacking.…”

Nanofibrous Hydrogel Nanocomposite Based on Strontium-Doped Bioglass Nanofibers for Bone Tissue Engineering Applications

“…Various studies have shown that BG-containing scaffolds have accelerated cell proliferation and good cell adherence [ 52 , 53 ]. For instance, Jayakumar et al [ 50 ] found that the embedment of BG particles into the Alg hydrogels matrix did not adversely affect the viability and compatibility of MG-63 cells and induced cell attachment and proliferation onto the scaffolds.…”

Melatonin enhances autologous adipose-derived stem cells to improve mouse ovarian function in relation to the SIRT6/NF-κB pathway

“…1 ), and then, the mice were randomly divided into four groups ( n = 10 each group): control group, PBS group, ADSCs group, and MLT-ADSCs group. According to a previous report [ 28 ], mice were intraperitoneally injected with CTX (120 mg/kg, Meilunbio) and busulfan (BUS, 30 mg/kg, Meilunbio) to establish a POI mode. The control group was intraperitoneally injected with an equal volume of 0.9% normal saline.…”