Stem cell therapy in diabetic men with erectile dysfunction: a 24-month follow-up of safety and efficacy of two intracavernous autologous bone marrow derived mesenchymal stem cells injections, an open label phase 2 clinical trial

BackgroundRecently we reported results of phase 1 pilot clinical trial of 2 consecutive intracavernous (IC) injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) for the first time in the treatment of diabetic patients with erectile dysfunction (DM-ED). In phase 2 of this study our aim is to evaluate long term safety and efficacy of IC injections of BM-MSC on additional eight patients with DM-ED.ResultsEach patient received 2 consecutive IC injections of BM-MSC and evaluated at 1, 3, 6, 12, and 24-month time points. Primary outcome was the tolerability and safety of stem cells therapy (SCT), while the secondary outcome was improvement of erectile function (EF) as assessed using the International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS) questionnaires, and Color Duplex Doppler Ultrasound (CDDU). IC injections of BM-MSCs was safe and well-tolerated. Minor local and short-term adverse events related to the bone marrow aspiration and IC injections were observed and treated conservatively. There were significant improvement in mean IIEF-5, EHS, all over the follow-up time points in comparison to the baseline. At 24-month follow up there were significant decline in the mean IIEF-5, and EHS compared to the baseline. The mean basal and 20-min peak systolic velocity was significantly higher at 3-month after the IC injections compared to baseline.ConclusionsThis phase 2 clinical trial confirmed that IC injections of BM-MSC are safe and improve EF. The decline in EF over time suggests a need for assessing repeated injections.Clinical trial registrationNCT02945462 ContexteR & eacute;cemment, nous avons rapport & eacute; les r & eacute;sultats d'un essai clinique pilote de phase 1, de 2 injections intracaverneuses (IC) cons & eacute;cutives de cellules souches m & eacute;senchymateuses autologues d & eacute;riv & eacute;es de la moelle osseuse (BM-MSC), pour la premi & egrave;re fois dans le traitement de patients diab & eacute;tiques atteints de dysfonction & eacute;rectile (DM-ED). Dans la phase 2 de cette & eacute;tude, notre objectif est d'& eacute;valuer l'innocuit & eacute; et l'efficacit & eacute; & agrave; long terme des injections IC de BM-MSC sur huit autres patients atteints de dysfonction & eacute;rectile.R & eacute;sultatsChaque patient a re & ccedil;u 2 injections IC cons & eacute;cutives de BM-MSC, et a & eacute;t & eacute; & eacute;valu & eacute; & agrave; des intervalles de temps de 1, 3, 6, 12 et 24 mois. Le crit & egrave;re de jugement principal & eacute;tait la tol & eacute;rance et l'innocuit & eacute; de la th & eacute;rapie par cellules souches, tandis que le crit & egrave;re de jugement secondaire & eacute;tait l'am & eacute;lioration de la fonction & eacute;rectile (FE) & eacute;valu & eacute;e & agrave; l'aide de l'indice international de la fonction & eacute;rectile-5 (IIEF-5), de questionnaires sur le score de duret & eacute; de l'& eacute;rection (EHS) et de l'& eacute;chographie Doppler duplex couleur. Les injections IC de BM-MSC se sont av & eacute;r & eacute;es s & ucirc;res et ont & eacute;t & eacute; bien tol & eacute;r & eacute;es. Des effets ind & eacute;sirables locaux et & agrave; court terme mineurs, li & eacute;s & agrave; l'aspiration de la moelle osseuse et aux injections d'IC, ont & eacute;t & eacute; observ & eacute;s et trait & eacute;s de mani & egrave;re conservatrice. Il y a eu une am & eacute;lioration significative des moyennes de l'IIEF-5 moyen, de l'EHS & agrave; tous les points de suivi par rapport & agrave; la l'& eacute;tat basal. A 24 mois de suivi, il y a eu une baisse significative de l'IIEF-5 moyen et de l'EHS par rapport & agrave; l'& eacute;tat basal. La moyenne se base et celle du pic maximal de la vitesse systolique & agrave; 20 minutes & eacute;taient significativement plus & eacute;lev & eacute;es 3 mois apr & egrave;s les injections de CI par rapport & agrave; l'& eacute;tat de base.ConclusionsCet essai clinique de phase 2 a confirm & eacute; que les injections de BM-MSC par injections intracaverneuses sont s & ucirc;res et am & eacute;liorent la fonction & eacute;rectile. La baisse de cette derni & egrave;re au fil du temps sugg & egrave;re une n & eacute;cessit & eacute; d'& eacute;valuation des injections r & eacute;p & eacute;t & eacute;es.