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

Asherman Syndrome (AS) is an acquired pathological condition affecting women’s reproductive health, triggered by the substitution of a bona fide endometrium with intrauterine adhesions that cause the uterine walls to adhere to each other. Clinically, AS results in menstrual abnormalities (amenorrhea or oligomenorrhea), pelvic pain, infertility, recurrent miscarriage and abnormal placentation. Autologous CD133+ bone marrow-derived stem cell (BMDSC) therapy has been designated as an Orphan Drug by the EMA and FDA for the treatment of AS. This phase 1/2, non-randomized, open-label, single-arm trial (EudraCT: 2016-003975-23) assessed the safety and efficacy of this novel therapy in 20 infertile women with moderate to severe AS, unresponsive to prior hysteroscopic treatments. Single-cell RNA sequencing of endometrium and organoids revealed partial reversion of AS-related changes, and mitochondrial variant tracking offered insights of CD133+ BMDSCs engraftment. These findings suggest that autologous CD133+ BMDSC therapy is a safe and effective treatment for AS.