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. 2024 Jul 5;34(1):13.
doi: 10.1186/s12610-024-00229-y.

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

Saddam Al Demour  1   2 , Sofia Adwan  3   4 , Hanan Jafar  3 , Hussam Alhawari  5 , Abdalla Awidi  6   7   8
Affiliations

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

Saddam Al Demour et al. Basic Clin Androl. .

Abstract
in English, French

Background: Recently 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.

Results: Each 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.

Conclusions: This 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 registration: NCT02945462.

RéSUMé: CONTEXTE: Récemment, nous avons rapporté les résultats d’un essai clinique pilote de phase 1, de 2 injections intracaverneuses (IC) consécutives de cellules souches mésenchymateuses autologues dérivées de la moelle osseuse (BM-MSC), pour la première fois dans le traitement de patients diabétiques atteints de dysfonction érectile (DM-ED). Dans la phase 2 de cette étude, notre objectif est d’évaluer l’innocuité et l’efficacité à long terme des injections IC de BM-MSC sur huit autres patients atteints de dysfonction érectile. RéSULTATS: Chaque patient a reçu 2 injections IC consécutives de BM-MSC, et a été évalué à des intervalles de temps de 1, 3, 6, 12 et 24 mois. Le critère de jugement principal était la tolérance et l’innocuité de la thérapie par cellules souches, tandis que le critère de jugement secondaire était l’amélioration de la fonction érectile (FE) évaluée à l’aide de l’indice international de la fonction érectile-5 (IIEF-5), de questionnaires sur le score de dureté de l’érection (EHS) et de l’échographie Doppler duplex couleur. Les injections IC de BM-MSC se sont avérées sûres et ont été bien tolérées. Des effets indésirables locaux et à court terme mineurs, liés à l’aspiration de la moelle osseuse et aux injections d’IC, ont été observés et traités de manière conservatrice. Il y a eu une amélioration significative des moyennes de l’IIEF-5 moyen, de l’EHS à tous les points de suivi par rapport à la l’état basal. A 24 mois de suivi, il y a eu une baisse significative de l’IIEF-5 moyen et de l’EHS par rapport à l’état basal. La moyenne se base et celle du pic maximal de la vitesse systolique à 20 minutes étaient significativement plus élevées 3 mois après les injections de CI par rapport à l’état de base. CONCLUSIONS: Cet essai clinique de phase 2 a confirmé que les injections de BM-MSC par injections intracaverneuses sont sûres et améliorent la fonction érectile. La baisse de cette dernière au fil du temps suggère une nécessité d’évaluation des injections répétées.

Keywords: Bone marrow-derived mesenchymal stem cells; Diabetic erectile dysfunction; Erectile dysfunction; Stem cells; Stem cells therapy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of patients during the study period
Fig. 2
Fig. 2
BM- MSCs. Representative light microscopy image of BM-MSCs at P2 before injection. BM, Bone marrow; MSCs, mesenchymal stem cells
Fig. 3
Fig. 3
Flow cytometric characterization of BM-MSCs. Positive expression of CD90, CD105, CD73, and CD44, and negative expression of hematopoietic markers: CD34, CD45, CD11b, CD19, and HLA-DR. MSCs, mesenchymal stem cells
Fig. 4
Fig. 4
Representative light microscopy images (40x) of the in vitro differentiation of BM-MSCs toward adipogenic and osteogenic lineages (a) Adipogenic differentiation of BM-MSCs stained with Oil Red O. b Osteogenic differentiation of BM-MSCs stained with Alizarin red. BM, Bone marrow; MSCs, mesenchymal stem cells
Fig. 5
Fig. 5
Changes in mean IIEF-5 and EHS scores after intracavernous injection BM-MS (n = 8). IIEF-5 range from 5 to 25 scores: severe (5-7), moderate (8-11), mild to moderate (12-16), mild (17-21), and no ED (22-25). EHS scale: 0, penis does not enlarge; 1, penis is larger but not hard; 2, penis is hard but not hard enough for penetration; 3, penis is hard enough for penetration but not completely hard; 4: penis is completely hard and fully rigid. Values are presented as mean ± standard deviation. The statistical analysis is performed via Wilcoxon signed rank test
Fig. 6
Fig. 6
Color Duplex Doppler Ultrasound of the penis (CDDU) before and after BM-MSC injections (n = 8). Peak systolic velocity (PSV), end-diastolic velocity (EDV), and the resistive index (RI), basal: before IC injection of 20 μg of alprostadil injection, 20 min : 20 min after IC injection of 20 μg of alprostadil injection. Values are presented as mean ± standard deviation. The statistical analysis is performed via Wilcoxon signed rank test
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