We designed a study to determine if autologous peripheral blood CD133+ bone marrow-derived stem cells (BMDSCs) could offer a safe and efficient therapeutic approach for infertility in patients with refractory Asherman’s syndrome (AS) and/or endometrial atrophy (EA). This was a prospective, experimental, non-controlled study that included 18 patients aged 30-45 years with refractory AS or EA; 16 of whom completed the study. An nitial hysteroscopic diagnosis was performed and BMDSC mobilization was performed by granulocyte-CSF injection, then CD133+ cells were isolated through peripheral blood aphaeresis to obtain a mean of 124.39 million cells (range 42-236), which were immediately delivered into the spiral arterioles by catheterization. Subsequently, endometrial treatment after stem cell therapy was assessed in terms of restoration of menses, endometrial thickness (by vaginal ultrasound), adhesion score (by hysteroscopy), neoangiogenesis and ongoing pregnancy rate after ART. In the first 3 months, autologous cell therapy increased the volume and duration of menses and improved endometrial thickness and angiogenesis of the endometrium while decreasing intrauterine adhesion scores.

Regarding reproductive outcomes, three patients became pregnant spontaneously, resulting in one baby boy born, one ongoing pregnancy and a miscarriage. Furthermore, seven pregnancies were obtained after fourteen embryo transfers, resulting in three biochemical pregnancies, one miscarriage, one ectopic pregnancy, one baby born and one ongoing pregnancy.

These results suggest that, despite the study limitations of a small sample size and lack of control, this novel autologous cell therapy may represent promising therapeutic option for patients with these so far-incurable pathologies.

A prospective experimental animal study was designed to investigate the engraftment and proliferation of superparamagnetic iron oxide nanoparticles (SPIOs)-labelled human CD133(+) bone marrow-derived stem cells (BMDSCs) in an animal model of Asherman syndrome (AS). Instillated cells were obtained from patients undergoing autologous cell therapy in refractory AS and endometrial atrophy, labelled with SPIOs and injected either via the intrauterine route (n = 5) or systemically through the tail vein (n = 5) in mice. The murine AS model showed accumulation of collagen and glycosaminoglycan deposits in the damaged horns by trichrome staining; 0.59% and 0.65% of the total number of human SPIOs labelled CD133(+) BMDSCs cells were present in the horns after intrauterine or tail vein injections, respectively. Interestingly, these cells engrafted around endometrial blood vessels and induced proliferation through the expression of Ki67 and paracrine factors such as thrombospondin 1 and insulin-like growth factor.

Pancreatic islet cell transplantation has been proposed as a treatment for diabetes. However, several problems, such as the shortage of cadaveric donors, can limit this therapeutic approach and require alternative solutions. There is recent evidence suggesting the presence of endometrial stromal stem cells (ESSC), since some cells have the ability to differentiate into mesodermal and ectodermal cellular lineages. In the current study we managed to differentiate human ESSC into insulin-secreting cells using a simpleprotocol that avoided transfection, assessing and confirming the expression of pan B-cell markers such as PAX4, PDX1, GLUT2, and insulin. Moreover, differentiated cells were injected into the kidney capsules of diabetic mice and human insulin was identified in serum. In addition, glucose levels stabilized within 5 weeks in mice transplanted with differentiated cells. On the other hand, mice transplanted with control cells lost weight, developed cataracts and developed progressive hyperglycemia. Therefore, the endometrium may become an easily accessible, renewable, and immunologically identical source of stem cells with potential therapeutic applications in diabetes..