Stem Cell Research & Therapy · Oct 21, 2026
Astaxanthin combined with 3D-bioprinted ovarian mimetic tissue ameliorates premature ovarian insufficiency via regulating the PI3K/AKT/mTOR signaling pathway
By Liu Y, Wang L, Liu C et al.
Premature ovarian insufficiency (POI) leads to severe ovarian injury and fertility decline. Conventional hormone replacement therapy cannot reverse tissue damage, and single stem cell or tissue engineering treatments have unsatisfactory clinical outcomes. A new treatment plan is needed to improve POI outcomes. Cisplatin was used to construct a POI rat model. Adipose-derived mesenchymal stem cells (ADSCs) were isolated, and ADSCs-incorporated 3D-bioprinted ovarian scaffolds were prepared. After identifying the optimal dose of astaxanthin (AST), rats were treated with AST, ovarian tissue fragments, 3D-bioprinted ovarian mimetic tissue, or their combination. Related hormonal, inflammatory, oxidative stress, and pathway protein indicators were evaluated. 100 mg/kg AST was confirmed as the optimal dose for follicle protection. The combined treatment group (AST+3D-bioprinted ovarian mimetic tissue) showed better improvements in body weight, estrous cycle, and follicle quantity than the monotherapy groups. Additionally, this combined approach effectively regulated inflammation, oxidative stress via PI3K/AKT/mTOR signaling pathway. AST combined with 3D-bioprinted ovarian mimetic tissue efficiently rescues ovarian function in POI rats. This synergistic strategy provides a promising multi-target option for clinical POI treatment.