PDF(825 KB)
Effect of culture supernatant of human umbilical cord mesenchymal stem cells on survival，apoptosis and endometrium receptivity of human endometrial stromal cells after treated with mifepristone
Mengxue WU,Shiling CHEN,Yan LIU,Xuguang MI,Xiuying LIN,Jianhua FU,Yanqiu FANG
PDF(825 KB)
PDF(825 KB)
Effect of culture supernatant of human umbilical cord mesenchymal stem cells on survival，apoptosis and endometrium receptivity of human endometrial stromal cells after treated with mifepristone
)Objective To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant （hUCMSCs-Sup） on the proliferation， apoptosis， and endometrium receptivity of the human endometrial stromal cells （hEndoSCs） treated with mifepristone （Ms）， and to clarify the possible mechanism. Methods The hEndoSCs were cultured in vitro and divided into control group and 40， 60， 80， and 100 μmol·L－1 Ms groups. The survival rates of the cells in various groups were detected by MTT assay. The hEndoSCs were divided into control group， 40 μmol·L－1 Ms group， and 60 μmol·L－1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry； the expression levels of apoptosis-related protein B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） proteins in the cells in various groups were detected by Western blotting method， and the ratio of Bcl-2/Bax was calculated. After treated with hUCMSCs-Sup， the hEndoSCs were divided into control group， Ms group， Ms+hUCMSCs-Sup group， and Ms+hUCMSCs-Sup+3-methyladenine （3-MA） group.The survival rates of the cells in various groups were detected by MTT assay；the apoptotic rates of the cells in various groups were detected by flow cytometry；the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ （LC3B-Ⅱ） and microtubule-associated protein 1 light chain 3B-I （LC3B-Ⅰ） proteins in the cells in various groups were detected by Western blotting method， and the ratio of LC3B-Ⅱ/LC3B-Ⅰ was calculated； the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR （RT-qPCR） method. Results Compared with control group， the survival rates of the cells in 40， 60， 80， and 100 μmol·L－1 Ms groups were significantly decreased （P<0.05）in a time-dependent and dose-dependent manner. Compared with control group， the apoptotic rates of the cells in 40 and 60 μmol·L－1 Ms groups were significantly increased （P<0.05）， and the ratios of Bcl-2/Bax were significantly decreased （P<0.05）. After treated with hUCMSCs-Sup， compared with control group， the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased （P<0.05）， the apoptotic rate was significantly increased （P<0.05）， and the expression levels of homeobox A10 （HOXA10）， leukemia inhibitory factor （LIF）， and integrin subunit beta 3 （ITGB3） mRNA in the cells were significantly decreased （P<0.05）；compared with Ms group， the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup group were significantly increased （P<0.05），the apoptotic rate was significantly decreased （P<0.05）， and the expression levels of HOXA10， LIF， and ITGB3 mRNA in the cells were significantly increased （P<0.05）； compared with Ms+hUCMSCs-Sup group， the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased （P<0.05）. Conclusion hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms，and increase the endometrium receptivity，and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.
Umbilical cord mesenchymal stem cell / Human endometrial stromal cell / Apoptosis / Autophagy / Endometrium receptivity
R711
| 1 | SHI Q， WANG D， DING X Y， et al. Exosome-shuttled miR-7162-3p from human umbilical cord derived mesenchymal stem cells repair endometrial stromal cell injury by restricting APOL6［J］. Arch Biochem Biophys， 2021， 707： 108887. |
| 2 | AZIZI R， AGHEBATI-MALEKI L， NOURI M， et al. Stem cell therapy in Asherman syndrome and thin endometrium： stem cell- based therapy［J］. Biomedecine Pharmacother， 2018， 102： 333-343. |
| 3 | LI X， LV H F， ZHAO R， et al. Recent developments in bio-scaffold materials as delivery strategies for therapeutics for endometrium regeneration［J］. Mater Today Bio， 2021， 11： 100101. |
| 4 | SHI Q， SUN B L， WANG D， et al. Circ6401， a novel circular RNA， is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis［J］. Stem Cell Res Ther， 2020，11（1）： 520. |
| 5 | WANG S， SHI C， CAI X H， et al. Human acellular amniotic matrix with previously seeded umbilical cord mesenchymal stem cells restores endometrial function in a rat model of injury［J］. Mediators Inflamm， 2021， 2021： 5573594. |
| 6 | 赵贵芳. 脐带间充质干细胞及其来源外泌体修复皮肤损伤的机制研究［D］. 长春： 吉林大学， 2016. |
| 7 | CHEN J， CHEN Y H， DU X， et al. Integrative studies of human cord blood derived mononuclear cells and umbilical cord derived mesenchyme stem cells in ameliorating bronchopulmonary dysplasia［J］. Front Cell Dev Biol， 2021， 9： 679866. |
| 8 | SHI M， LI Y Y， XU R N， et al. Mesenchymal stem cell therapy in decompensated liver cirrhosis： a long-term follow-up analysis of the randomized controlled clinical trial［J］. Hepatol Int， 2021， 15（6）： 1431-1441. |
| 9 | DING L， HAN D M， ZHENG X L， et al. Infusion of haploidentical hematopoietic stem cells combined with mesenchymal stem cells for treatment of severe aplastic anemia in adult patients yields curative effects［J］. Cytotherapy， 2022， 24（2）： 205-212. |
| 10 | LV X L， WANG L M， ZOU X R， et al. Umbilical cord mesenchymal stem cell therapy for regenerative treatment of rheumatoid arthritis： opportunities and challenges［J］. Drug Des Devel Ther， 2021， 15： 3927-3936. |
| 11 | SONG M， LIM J， YU H Y， et al. Mesenchymal stem cell therapy alleviates interstitial cystitis by activating Wnt signaling pathway［J］.Stem Cells Dev，2015，24（14）： 1648-1657. |
| 12 | XIANG E， HAN B， ZHANG Q， et al. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis［J］. Stem Cell Res Ther， 2020， 11（1）： 336. |
| 13 | ZHANG L， LI Y， GUAN C Y， et al. Therapeutic effect of human umbilical cord-derived mesenchymal stem cells on injured rat endometrium during its chronic phase［J］. Stem Cell Res Ther， 2018， 9（1）： 36. |
| 14 | KIM H， SHIN J E， KOO H S， et al. Effect of autologous platelet-rich plasma treatment on refractory thin endometrium during the frozen embryo transfer cycle： a pilot study［J］. Front Endocrinol， 2019， 10： 61. |
| 15 | WANG J Y， HU R M， XING Q， et al. Exosomes derived from umbilical cord mesenchymal stem cells alleviate mifepristone-induced human endometrial stromal cell injury［J］. Stem Cells Int， 2020， 2020： 6091269. |
| 16 | SONG Y T， LIU P C， TAN J， et al. Stem cell-based therapy for ameliorating intrauterine adhesion and endometrium injury［J］.Stem Cell Res Ther，2021，12（1）： 556. |
| 17 | XIA Z， XIAO J， CHEN Q. Solving the puzzle： what is the role of progestogens in neovascularization？［J］. Biomolecules， 2021， 11（11）： 1686. |
| 18 | LIANG L L， WANG L， ZHOU S H， et al. Exosomes derived from human umbilical cord mesenchymal stem cells repair injured endometrial epithelial cells［J］. J Assist Reprod Genet， 2020， 37（2）： 395-403. |
| 19 | 邱纪玲， 王晓彤， 周灏雯， 等. 间充质干细胞条件培养液修复多种疾病损伤的潜能［J］. 中国组织工程研究， 2019， 23（29）： 4743-4748. |
| 20 | PHINNEY D G， PITTENGER M F. Concise review： MSC-derived exosomes for cell-free therapy［J］. Stem Cells， 2017， 35（4）： 851-858. |
| 21 | ZHAO P， CHEN Y F， YUE Z J， et al. Bone marrow mesenchymal stem cells regulate stemness of multiple myeloma cell lines via BTK signaling pathway［J］. Leuk Res， 2017， 57： 20-26. |
| 22 | SU Y， ZHANG J J， HE J L， et al. Endometrial autophagy is essential for embryo implantation during early pregnancy［J］. J Mol Med， 2020， 98（4）： 555-567. |
| 23 | CHOI J， JO M， LEE E， et al. Differential induction of autophagy by mTOR is associated with abnormal apoptosis in ovarian endometriotic cysts［J］. Mol Hum Reprod， 2014， 20（4）： 309-317. |
| 24 | POPLI P， SUN A J， KOMMAGANI R. The multifaceted role of autophagy in endometrium homeostasis and disease［J］. Reprod Sci， 2022， 29（4）： 1054-1067. |
| 25 | LU H， YANG H L， ZHOU W J， et al. Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence［J］. Autophagy， 2021， 17（9）： 2511-2527. |
| 26 | MROZIKIEWICZ A E， O?AROWSKI M， J?DRZEJCZAK P. Biomolecular markers of recurrent implantation failure-a review［J］. Int J Mol Sci， 2021， 22（18）： 10082. |
| 27 | CELIK O， UNLU C， OTLU B， et al. Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression［J］. Fertil Steril， 2015， 104（2）： 356-365. |
| 28 | NICOLA N A， BABON J J. Leukemia inhibitory factor （LIF）［J］. Cytokine Growth Factor Rev， 2015， 26（5）： 533-544. |
| 29 | LI B N， ZHANG Q W， SUN J Y， et al. Human amniotic epithelial cells improve fertility in an intrauterine adhesion mouse model［J］. Stem Cell Res Ther， 2019， 10（1）： 257. |
| 30 | DANIELSSON K G， MARIONS L， BYGDEMAN M. Effects of mifepristone on endometrial receptivity［J］. Steroids， 2003， 68： 1069-1075. |
| 31 | WANG G L， REN C E， JIANG J Y. Effects of bone marrow mesenchymal stem cells on repair and receptivity of damaged endometrium in rats［J］. J Obstet Gynaecol Res， 2021， 47（9）： 3223-3231. |
/
| 〈 |
|
〉 |
AI Summary
