Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial.
Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial.
复制标题
DOI：
10.1186/s13287-018-0904-3
复制
发表时间：
2018-07-11
影响因子：
7.5
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Cao Y;Sun H;Zhu H;Zhu X;Tang X;Yan G;Wang J;Bai D;Wang J;Wang L;Zhou Q;Wang H;Dai C;Ding L;Xu B;Zhou Y;Hao J;Dai J;Hu Y
宫腔粘连（IUA）是子宫不孕症的最常见原因，是由子宫内膜严重损伤后子宫内膜纤维化再生引起的。虽然目前使用不同类型的自体干细胞的干细胞治疗方案在IUA患者中表现出一些有益的结果，但报告的缺点包括可变的治疗效果，侵入性和治疗不可用性。因此，开发新的治疗性干细胞疗法对改善临床结果至关重要。26例复发性IUA引起的不孕患者参加了这项前瞻性、非对照、I期临床试验，随访30个月。在手术过程中，1 × 107脐带来源的间充质干细胞（UC-MSCs），负载在胶原支架上，移植到子宫腔后，粘附分离程序。在治疗前和治疗后3个月，对患者的病史、体格检查、子宫内膜厚度、宫腔粘连评分以及与子宫内膜增殖和分化相关的生物学分子进行评估。术后3个月，患者子宫内膜最大厚度较治疗前平均增加，宫腔粘连评分较治疗前下降。组织学研究显示，ERα（雌激素受体α）、波形蛋白、Ki 67和vWF（血管性血友病因子）表达水平上调，Δ NP 63表达水平下调，这表明治疗后子宫内膜增殖、分化和新生血管的改善。DNA短串联重复序列（STR）分析显示再生的子宫内膜仅含有患者DNA。到30个月随访期结束时，26名患者中有10名怀孕，其中8名分娩了无明显出生缺陷和胎盘并发症的活婴，1名患者处于妊娠晚期，1名患者在7周时自然流产。将负载于可降解胶原支架上的临床级UC-MSCs移植到粘连松解术后复发性IUA患者的宫腔内是一种安全有效的治疗方法。Clinicaltrials.gov. NCT 02313415，于2014年12月6日注册。本文的在线版本（10.1186/s13287-018-0904-3）包含补充材料，可供授权用户使用。
Intrauterine adhesions (IUA) are the most common cause of uterine infertility and are caused by endometrium fibrotic regeneration following severe damage to the endometrium. Although current stem cell treatment options using different types of autologous stem cells have exhibited some beneficial outcomes in IUA patients, the reported drawbacks include variable therapeutic efficacies, invasiveness and treatment unavailability. Therefore, the development of new therapeutic stem cell treatments is critical to improving clinical outcomes. Twenty-six patients who suffered from infertility caused by recurrent IUA were enrolled in this prospective, non-controlled, phase I clinical trial with a 30-month follow-up. During the procedure, 1 × 107 umbilical cord-derived mesenchymal stromal cells (UC-MSCs), loaded onto a collagen scaffold, were transplanted into the uterine cavity following an adhesion separation procedure. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and the biological molecules related to endometrial proliferation and differentiation were assessed both before and 3 months after cell therapy. No treatment-related serious adverse events were found. Three months after the operation, the average maximum endometrial thickness in patients increased, and the intrauterine adhesion score decreased compared to those before the treatment. A histological study showed the upregulation of ERα (estrogen receptor α), vimentin, Ki67 and vWF (von Willebrand factor) expression levels and the downregulation of ΔNP63 expression level, which indicates an improvement in endometrial proliferation, differentiation and neovascularization following treatment. DNA short tandem repeat (STR) analysis showed that the regenerated endometrium contained patient DNA only. By the end of the 30-month follow-up period, ten of the 26 patients had become pregnant, and eight of them had delivered live babies with no obvious birth defects and without placental complications, one patient in the third trimester of pregnancy, and one had a spontaneous abortion at 7 weeks. Transplanting clinical-grade UC-MSCs loaded onto a degradable collagen scaffold into the uterine cavity of patients with recurrent IUA following adhesiolysis surgery is a safety and effective therapeutic method. Clinicaltrials.gov. NCT02313415, Registered December 6, 2014. The online version of this article (10.1186/s13287-018-0904-3) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
14
作者：
Li, Xinan;Sun, Haixiang;Hu, Yali
通讯作者：
Hu, Yali
影响因子：
--
作者：
Singh N;Mohanty S;Seth T;Shankar M;Bhaskaran S;Dharmendra S
通讯作者：
Dharmendra S
影响因子：
6.7
作者：
Hanstede, Miriam M. E.;van der Meij, Eva;Emanuel, Mark Hans
通讯作者：
Emanuel, Mark Hans
影响因子：
4
作者：
Gauthaman, Kalamegam;Fong, Chui-Yee;Bongso, Ariff
通讯作者：
Bongso, Ariff
影响因子：
6.1
作者：
Tan, Jichun;Li, Pingping;Kong, Lin
通讯作者：
Kong, Lin