Mesenchymal stem cell-derived angiogenin promotes primodial follicle survival and angiogenesis in transplanted human ovarian tissue

Reproductive Biology and Endocrinology

Research

Hsun-Ming Chang¹  Tianren Wang²  Yaoyao Zhang³  Rong Li³  Jie Yan³  Jie Qiao³  Cuilin Lu³  Tailang Yin³  Liying Yan³  Xiaohui Zhu³  Xi Xia⁴ 

[1] Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, V5Z4H4, Vancouver, Canada;Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, 100191, Beijing, China;Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, 100191, Beijing, China;Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Shengjing Hospital of China Medical University, 100004, Shenyang, China;Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, 100191, Beijing, China;Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, 100191, Beijing, China;Key Laboratory of Assisted Reproduction, Ministry of Education, 100191, Beijing, China;Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No.49 North HuaYuan Road, HaiDian District, 100191, Beijing, China;Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Shenzhen Hospital, No.1120 Lotus Road, FuTian District, 518000, Shenzhen, Guangdong, China;

关键词: Ovarian tissue transplantation;    Mesenchymal stem cell;    Follicle survival;    Fertility preservation;    Angiogenin;   

DOI  :  10.1186/s12958-017-0235-8

 received in 2016-11-08, accepted in 2017-02-23,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundWe have recently reported that human bone marrow-derived mesenchymal stem cells (MSCs) facilitate angiogenesis and prevent follicle loss in xenografted human ovarian tissues. However, the mechanism underlying this effect remains to be elucidated. Thus, determining the paracrine profiles and identifying the key secreted factors in MSCs co-transplanted with ovarian grafts are essential for the future application of MSCs.MethodsIn this study, we used cytokine microarrays to identify differentially expressed proteins associated with angiogenesis in frozen-thawed ovarian tissues co-transplanted with MSCs. The function of specific secreted factors in MSCs co-transplanted with human ovarian tissues was studied via targeted blockade with short-hairpin RNAi and the use of monoclonal neutralizing antibodies.ResultsOur results showed that angiogenin (ANG) was one of the most robustly up-regulated proteins (among 42 protein we screened, 37 proteins were up-regulated). Notably, the targeted depletion of ANG with short-hairpin RNAi (shANG) or the addition of anti-ANG monoclonal neutralizing antibodies (ANG Ab) significantly reversed the MSC-stimulated angiogenesis, increased follicle numbers and protective effect on follicle apoptosis.ConclusionOur results indicate that ANG plays a critical role in regulating angiogenesis and follicle survival in xenografted human ovarian tissues. Our findings provide important insights into the molecular mechanism by which MSCs promote angiogenesis and follicle survival in transplanted ovarian tissues, thus providing a theoretical basis for their further application.

【 授权许可】

CC BY   
© The Author(s). 2017