title: Safety of Intracavernous Bone Marrow-Mononuclear Cells for Postradical Prostatectomy Erectile Dysfunction: An Open Dose-Escalation Pilot Study.
abstract: Evidence from animal models replicating postradical prostatectomy erectile dysfunction (pRP-ED) suggests intracavernous injection of bone marrow-mononuclear cells (BM-MNCs) as a promising treatment approach for pRP-ED. We conducted a phase 1/2 pilot clinical trial of intracavernous autologous BM-MNC injection to treat pRP-ED (NCT01089387). Twelve patients with localized prostate cancer and vasculogenic pRP-ED refractory to maximal medical treatment were divided into four equal groups treated with escalating BM-MNC doses (2×10(7), 2×10(8), 1×10(9), 2×10(9)). Tolerance was the primary endpoint. Secondary endpoints were the effects on erectile function and penile vascularization at 6 mo, as assessed using the International Index of Erectile Function-15 and Erection Hardness Scale questionnaires, and color duplex Doppler ultrasound. We measured the peak systolic velocity in cavernous arteries and assessed endothelial function using the penile nitric oxide release test. No serious side effects occurred. At 6 mo versus baseline, significant improvements of intercourse satisfaction (6.8±3.6, 3.9±2.5, p=0.044) and erectile function (17.4±8.9, 7.3±4.5, p=0.006) domains of the International Index of Erectile Function-15 and Erection Hardness Scale (2.6±1.1, 1.3±0.8, p=0.008) were observed in the total population. Spontaneous erections showed significantly greater improvement with the higher doses. Clinical benefits were associated with improvement of peak systolic velocity and of % penile nitric oxide release test and sustained after 1 yr. Our results need to be confirmed by phase 2 clinical trials.
  
  
  
  We report a phase 1/2 pilot clinical trial investigating cell therapy with injection of bone marrow mononucleated cells to treat postradical prostatectomy erectile dysfunction. No serious side effects occurred. Improvements of erectile function and penile vascularization were noted. Further studies are required to confirm these preliminary results.
authors.affiliation: APHP, Urology Department, Henri Mondor Teaching Hospital, Créteil, France. Electronic address: rene.yiou@hmn.aphp.fr.
authors.forename: René
authors.initials: R
authors.lastname: Yiou
authors.affiliation: APHP, Department of Physiology, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Leila
authors.initials: L
authors.lastname: Hamidou
authors.affiliation: Etablissement Français du Sang, Unité d'Ingénierie et de thérapie cellulaire, Créteil, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Birebent
authors.affiliation: APHP, CIC-P006, and CIC-BT 504, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Dalila
authors.initials: D
authors.lastname: Bitari
authors.affiliation: APHP, CIC-P006, and CIC-BT 504, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lecorvoisier
authors.affiliation: APHP, Anesthesiology Department, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Contremoulins
authors.affiliation: APHP, Urology Department, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Muhieddine
authors.initials: M
authors.lastname: Khodari
authors.affiliation: INSERM, U955, UPEC, Créteil, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Rodriguez
authors.affiliation: APHP, Urology Department, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Augustin
authors.affiliation: APHP, Department of Public Health of Statistics, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Roudot-Thoraval
authors.affiliation: APHP, Urology Department, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.affiliation: Etablissement Français du Sang, Unité d'Ingénierie et de thérapie cellulaire, Créteil, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Rouard
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003075:Coitus; D007172:Erectile Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology / Q000628:therapy*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010410:Penile Erection; D010413:Penis / Q000098:blood supply* / Q000000981:diagnostic imaging; D010865:Pilot Projects; D011468:Prostatectomy / Q000009:adverse effects; D012039:Regional Blood Flow; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D018615:Ultrasonography, Doppler, Color
keywords: Bone marrow; Cavernous nerves; Cell therapy; Erectile dysfunction; Radical prostatectomy; Stem cell