Adipose-derived stem cells promote survival, growth, and maturation of early-stage murine follicles

Abstract

BackgroundPremature ovarian insufficiency is a common complication of anticancer treatments in young women and girls. The ovary is a complex, highly regulated reproductive organ, whose proper function is contingent upon the bidirectional endocrine, paracrine, and autocrine signaling. These factors facilitate the development of the follicles, the functional units of the ovary, to progress from the gonadotropin-independent, paracrine-controlled early stage to the gonadotropin-dependent, endocrine-controlled later stage. We hypothesized that the low survival rate of individually cultured early-stage follicles could be improved with co-culture of adipose-derived stem cells (ADSCs) that secrete survival- and growth-promoting factors.Materials and methodsOvarian follicles ranging from 85 to 115 μm in diameter, from 10- to 12-day-old B6CBAF1 mice were mechanically isolated and co-encapsulated with ADSCs within alginate-based 3D culture system. The follicles were cultured for 14 days, imaged using light microscopy every 2 days, and matured at the end. Follicle media were changed every 2 days and collected for hormone measurements. Follicle diameter, morphology, number of transzonal projections, and survival and maturation rates were recorded. Statistical analyses using one- and two-way ANOVA were performed to compare hormone levels, survival of the follicles and ADSCs, oocyte maturation rates, and follicle growth.ResultsThe co-encapsulation of the follicles with ADSCs increased follicle survival, ranging from 42.4% for the 86–95 μm to 86.2% for the 106–115-μm follicle size group. Co-culture also improved the follicle growth, the rate of antrum formation and oocyte maturation compared to the follicles cultured alone. The levels of androstenedione, estradiol, and progesterone of co-encapsulated follicles increased progressively with time in culture.ConclusionsTo our knowledge, this is the first report of an in vitro system utilizing mouse adipose-derived stem cells to support the development of the mouse follicles. Our findings suggest that co-encapsulation of ADSCs with early-stage follicles supports follicular development, through secretion of cytokines that promote follicular survival, antrum formation, and meiotic competence. The unique 3D culture system that supports the survival of both cell types has translational implications, as ADSCs could be used as an autologous source for in vitro maturation of early-stage human follicles.Electronic supplementary materialThe online version of this article (10.1186/s13287-019-1199-8) contains supplementary material, which is available to authorized users.

Conditioned medium-electrospun fiber biomaterials for skin regeneration

“…For the in vivo animal experiment, mouse ADSCs (mADSCs) were isolated from the subcutaneous adipose tissue in groin of C57BL/6 mouse [ 32 ]. The methods for conditioned medium of mADSCs (mADSC-CM) collection and the fabrication for mADSC-CM loaded electrospun membranes is the same as that we described in the section of experiments in vitro .…”

How to Support the In Vitro Culture of Human Ovarian Cells and Follicles? A Preliminary Step for Assembling an Artificial Ovary

“…It was shown that ATDCs can promote the early stages of follicles survival, growth and maturation. They secret factors which promote the early stages of follicle growth (50). Also, AFDCs have shown to preserve ovarian follicle after chemotherapy (51) and they have potential to differentiate into primordial follicle (52).…”

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

“…As we all know, cell therapy strategy has been reported to be a strongly effective way in the treatment of different diseases [16,18,33,34]. MSCs act as a kind of adult stem/stromal cells that could differentiate into specific tissues cells induced by local microenvironment when they were damaged, and could secrete various cytokines.…”