title: Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial.
abstract: BACKGROUND
  Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction.
  
  
  METHODS
  Seventeen men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5-18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study is registered with ClinicalTrials.gov, NCT02240823.
  
  
  RESULTS
  Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered their erectile function and were able to accomplish sexual intercourse. Post-hoc stratification according to urinary continence status was performed. Accordingly, for continent men (median IIEFinclusion = 7 (95% CI 5-12), 8 out of 11 men recovered erectile function (IIEF6months = 17 (6-23)), corresponding to a mean difference of 0.57 (0.38-0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5-6); mean difference 1 (95% CI 0.85-1.18), p > 0.9999).
  
  
  CONCLUSIONS
  In this phase I trial a single intracavernosal injection of freshly isolated autologous ADRCs was a safe procedure. A potential efficacy is suggested by a significant improvement in IIEF-5 scores and erectile function. We suggest that ADRCs represent a promising interventional therapy of ED following prostatectomy.
  
  
  BACKGROUND
  Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society.
authors.affiliation: Department of Urology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Martha Kirstine
authors.initials: MK
authors.lastname: Haahr
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark.
authors.forename: Charlotte Harken
authors.initials: CH
authors.lastname: Jensen
authors.affiliation: Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Navid Mohamadpour
authors.initials: NM
authors.lastname: Toyserkani
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Ditte Caroline
authors.initials: DC
authors.lastname: Andersen
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Damkier
authors.affiliation: Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Jens Ahm
authors.initials: JA
authors.lastname: Sørensen
authors.affiliation: Department of Urology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Lund
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Institute of Molecular Medicine, University of Southern Denmark, Winsloewparken 21 3rd, 5000 Odense C, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark.
authors.forename: Søren Paludan
authors.initials: SP
authors.lastname: Sheikh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000637:transplantation; D000368:Aged; D002454:Cell Differentiation / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000150:complications / Q000601:surgery / Q000628:therapy*; D044968:Regenerative Medicine / Q000379:methods; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*
keywords: ADRC, adipose-derived regenerative cells; Adipose-derived regenerative cells; Adipose-derived stem cells; Adipose-derived stromal vascular fraction; BMI, body mass index; CFU-F, fibroblastoid colony forming units; Cell therapy; Clinical trial; ED, erectile dysfunction; EHS, erection hardness score; Erectile dysfunction; ICIQ-UI SF, incontinence questionnaire – urinary incontinence – short form questionnaire; IIEF-5, international index of erectile function-5; LUTS, lower urinary tract symptoms; NSAID, nonsteroidal antiinflammatory drug; PDE-5, phosphodiesterase-5; RP, radical prostatectomy; SVF, stromal vascular fraction