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Clinical Trial
. 2018 Jul 11;9(1):192.
doi: 10.1186/s13287-018-0904-3.

Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial

Yun Cao  1 , Haixiang Sun  1 , Hui Zhu  1 , Xianghong Zhu  1 , Xiaoqiu Tang  1 , Guijun Yan  1 , Jingmei Wang  1 , Donghui Bai  2 , Juan Wang  2 , Liu Wang  2 , Qi Zhou  2 , Huiyan Wang  1 , Chengyan Dai  1 , Lijun Ding  1 , Biyun Xu  1 , Yan Zhou  3 , Jie Hao  4 , Jianwu Dai  5 , Yali Hu  6   7
Affiliations
Clinical Trial

Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial

Yun Cao et al. Stem Cell Res Ther. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: Clinicaltrials.gov . NCT02313415 , Registered December 6, 2014.

Keywords: Asherman syndrome; Collagen scaffold; Intrauterine adhesions; UC-MSCs; Uterine infertility.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethics Committee on Human Research of the Nanjing Drum Tower Hospital (No. 201406401). Patients were assessed for eligibility between November 2014 and February 2015 (NCT 02313415). Informed consent for the cell therapy performed in the current study was obtained from every patient. The human newborn umbilical cord tissues used in this study were obtained from the 306th Hospital (Beijing, China) and cultured by the Institute of Zoology, Chinese Academy of Sciences (Beijing, China). No tissues were obtained from prisoners.

Consent for publication

Consent for publication was also obtained from every patient.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig 1
Fig 1
A flow chart of the patient enrollment process. UC-MSC umbilical cord-derived mesenchymal stem cells
Fig. 2
Fig. 2
Hysteroscopic inspection images from all 25 patients, before and after UC-MSC/collagen treatment
Fig. 3
Fig. 3
Blood flow of ten patients before and after UC-MSC/collagen treatment by Doppler ultrasound
Fig. 4
Fig. 4
Immunohistochemical staining of ERα, Ki67, vWF and ΔNp63 on endometrial biopsy samples obtained from patients before and after UC-MSC/collagen treatment. Scale bar: 100 μm. ERα estrogen receptor alpha, vWF von Willebrand factor
See this image and copyright information in PMC

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