Unresponsive thin endometrium caused by Asherman syndrome treated with umbilical cord mesenchymal stem cells on collagen scaffolds: a pilot study

Stem Cell Research & Therapy

Huaying Yu¹  Jing Li¹  Yanling Zhang¹  Libing Shi¹  Feng Zhou¹  Wenzhi Xu¹  Yongdong Dai¹  Lijuan Zhao¹  Yinli Zhang¹  Liaobing Xin¹  Yibin Pan¹  Songying Zhang¹  Xiaona Lin¹  Mei Pan²  Jia Shen³  Min Lu³ 

[1] Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, NO.3 Qingchun East Road, Shangcheng District, 310016, Hangzhou, People’s Republic of China;Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, People’s Republic of China;Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China;Zhejiang Gene Stem Cell Biotech Co. Ltd., Zhejiang, Hangzhou, People’s Republic of China;

关键词: Thin endometrium;    Asherman syndrome;    Umbilical cord mesenchymal stem cells;    Collagen scaffolds;    Endometrial regeneration;    Cell therapy;   

DOI  :  10.1186/s13287-021-02499-z

来源: Springer

【 摘 要 】

BackgroundUnresponsive thin endometrium caused by Asherman syndrome (AS) is the major cause of uterine infertility. However, current therapies are ineffective. This study is to evaluate the effect of transplantation with collagen scaffold/umbilical cord mesenchymal stem cells (CS/UC-MSCs) on this refractory disease.MethodsEighteen infertile women with unresponsive thin endometrium, whose frozen–thawed embryo transfers (FETs) were cancelled due to reduced endometrial thickness (ET ≤ 5.5 mm), were enrolled in this before and after self-control prospective study. Hysteroscopic examination was performed to confirm no intrauterine adhesions, then twenty million UC-MSCs loaded onto a CS were transplanted into the uterine cavity in two consecutive menstrual cycles. Then uterine cavity was assessed through hysteroscopy after two transplants. FETs were performed in the following cycle. Pregnancy outcomes were followed up. Endometrial thickness, uterine receptivity and endometrial angiogenesis, proliferation and hormone response were compared before and after treatment.ResultsSixteen patients completed the study. No treatment-related serious adverse events occurred. Three months after transplantation, the average ET increased from 4.08 ± 0.26 mm to 5.87 ± 0.77 mm (P < 0.001). Three of 15 patients after FET got pregnant, of whom 2 gave birth successfully and 1 had a miscarriage at 25 weeks’ gestation. One of 2 patients without FET had a natural pregnancy and gave birth normally after transplantation. Immunohistochemical analysis showed increased micro-vessel density, upregulated expression of Ki67, estrogen receptor alpha, and progesterone receptor, indicating an improvement in endometrial angiogenesis, proliferation, and response to hormones.ConclusionCS/UC-MSCs is a promising and potential approach for treating women with unresponsive thin endometrium caused by AS.Trial registrationClinicalTrials.gov NCT03724617. Registered on 26 October 2018—prospectively registered, https://register.clinicaltrials.gov/

【 授权许可】

CC BY