Autologous cell therapy with CD133+ bone marrow-derived stem cells for Asherman Syndrome: a phase 1/2 trial

Autologous CD133 + bone marrow-derived stem cell (BMDSC) therapy has been designated an Orphan Drug by the EMA and FDA for the treatment of Asherman Syndrome (AS). This phase 1/2, non-randomized, open-label, single-arm trial assessed the safety, efficacy and biological plausibility of this novel therapy in 20 infertile women with moderate to severe AS unresponsive to prior hysteroscopic treatments. The primary endpoint was safety, with doses ranging from 31 to 212 × 10⁶ cells being well tolerated; reversible limb paresthesia was the most common adverse event. Secondary endpoints demonstrated significant improvements in endometrial morphometry, thickness (3.80 ± 0.95 mm to 5.29 ± 0.77 mm, p  < 0.05), endometrial volume (1.26 cm³ to 2.78 cm³, p  < 0.05), and hysteroscopic scores (8.0 ± 3.17 to 4.42 ± 2.09, p  < 0.05). Clinically, menstruation and reproductive function were restored, culminating in six live births following embryo transfer. Single-cell RNA sequencing of endometrium and organoids pre- and post-treatment revealed partial reversion of AS-related changes. Additionally, mitochondrial variant tracking offered insights into the engraftment of transplanted CD133 + BMDSCs. These findings suggest that autologous CD133 + BMDSC therapy is a safe and effective treatment for moderate to severe AS, warranting further investigation in larger trials.