根治性前列腺切除术后勃起功能障碍患者单次海绵体内注射自体脂肪来源的再生细胞的安全性和潜在疗效：一项开放性 I 期临床试验。

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.

机构信息

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.

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.

出版信息

EBioMedicine. 2016 Jan 19;5:204-10. doi: 10.1016/j.ebiom.2016.01.024. eCollection 2016 Mar.

DOI:10.1016/j.ebiom.2016.01.024

PMID:27077129

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4816754/

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.

FINDINGS

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).

INTERPRETATION

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.

FUNDING

Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society.

摘要

背景

前列腺癌是男性最常见的癌症，根治性前列腺切除术（RP）常导致勃起功能障碍（ED）和生活质量显著下降。目前干预措施的疗效并不令人满意，这种情况存在未满足的医疗需求。使用脂肪来源的干细胞治疗 ED 的临床前研究显示出有希望的结果。在此，我们报告了一项使用脂肪抽吸术刚分离的自体脂肪来源再生细胞（ADRCs）进行的 1 期人体临床试验结果。

方法

17 名患有 RP 后 ED 的男性，在常规治疗后无法恢复，参加了一项前瞻性 1 期开放标签和单臂研究。所有受试者均在入组前 5-18 个月接受 RP，并在腔内移植后随访 6 个月。分析 ADRC 中是否存在干细胞表面标志物、活力和分化能力。主要终点是细胞治疗的安全性和耐受性，次要结局是勃起功能的改善。报告任何不良事件，并通过 IIEF-5 评分评估勃起功能。该研究在 ClinicalTrials.gov 注册，NCT02240823。

结果

腔内注射 ADRC 耐受性良好，仅在 1 个月评估时报告了与脂肪抽吸和细胞注射相关的轻微事件，但之后的时间点没有报告。在整个研究期间，17 名男性中有 8 名恢复了勃起功能并能够进行性交。根据尿控状态进行了事后分层。因此，对于有尿控的男性（纳入时 IIEFinclusion = 7（95%CI 5-12），11 名男性中有 8 名恢复了勃起功能（IIEF6 个月= 17（6-23）），平均差异为 0.57（0.38-0.85；p=0.0069），与纳入时相比。相比之下，尿失禁男性没有恢复勃起功能（纳入时 IIEF1/3/6 个月= 5（95%CI 5-6）；平均差异 1（95%CI 0.85-1.18），p＞0.9999）。