Human mesenchymal stem cells in spheroids improve fertility in model animals with damaged endometrium

Abstract

BackgroundAsherman’s syndrome (AS) is one of the gynecological disorders caused by the destruction of the endometrium. For some cases of AS available surgical methods and hormonal therapy are ineffective. Stem cell transplantation may offer a potential alternative for AS cure.MethodsHuman endometrial mesenchymal stem cells (eMSC) organized in spheroids were transplanted in rats with damaged endometrium modeled on AS. Treatment response was defined as pregnancy outcome and litter size.ResultsApplication of eMSC in spheroids significantly improved the rat fertility with the AS model. eMSC organized in spheroids retain all properties of eMSC in monolayer: growth characteristics, expression of CD markers, and differentiation potential. Synthesis of angiogenic and anti-inflammatory factors drastically increased in eMSC assembled into spheroids.ConclusionsHuman endometrial mesenchymal stem cells (eMSC) can be successfully applied for Asherman’s syndrome (AS) treatment in the rat model. eMSC organized in spheroids were more therapeutically effective than the cells in monolayer. After transplantation of eMSC in spheroids the pregnancy outcome and litter size in rats with AS was higher than in rats that received autologous rat bone marrow cells. It suggests the therapeutic plausibility of heterologous eMSC in case of failure to use autologous cells.

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…Moreover, MenSCs treatment, along with hormonal stimulation, was shown to improve endometrium structure and fertility potential in women with Asherman syndrome (84). Another study reported that MenSCs treatment increases fertility through induction of angiogenic and antiinflammatory factors in a rat model of Asherman syndrome (85). Other work has found that MenSCs produce functional spheroids, which appear to be essential for their observed therapeutic effects (86).…”

Mini-Review of the New Therapeutic Possibilities in Asherman Syndrome—Where Are We after One Hundred and Twenty-Six Years?

“…In both experimental models [ 103 , 104 , 105 , 106 , 107 ] and humans [ 108 , 109 , 110 , 111 ] the regeneration of endometrium through a stem cell approach has been evaluated. Mesenchymal, bone-marrow-derived stem cells and menstrual blood-derived stromal cells were investigated in this context.…”

“…Mesenchymal, bone-marrow-derived stem cells and menstrual blood-derived stromal cells were investigated in this context. For this, distinct methods such as transmyometrial administration to the subendometrial area [ 109 ], direct installation of stromal cells in the uterine cavity after endometrial scratching [ 111 ], and infusion in spiral arterioles through catheters [ 110 ] have been put in application, even stem cells arranged in spheroids for a rat model [ 107 ]. Thus, the first results were not long in coming.…”

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…Moreover, MenSCs treatment, along with hormonal stimulation, was shown to improve endometrium structure and fertility potential in women with Asherman syndrome [ 91 ]. Domnina et al, reported that MenSCs treatment increases fertility through induction of angiogenic and anti-inflammatory factors in a rat model of Asherman syndrome [ 92 ]. Other work has found that MenSCs produce functional spheroids, which appear to be essential for their observed therapeutic effects [ 93 ].…”