Effects of human umbilical cord mesenchymal stem cells derived from exosomes on migration ability of endometrial glandular epithelial cells

Feng,Ying; Zhan,Fuliang; Zhong,Yanying; Tan,Buzhen

doi:10.3892/mmr.2020.11137

Effects of human umbilical cord mesenchymal stem cells derived from exosomes on migration ability of endometrial glandular epithelial cells

Authors:
- Ying Feng
- Fuliang Zhan
- Yanying Zhong
- Buzhen Tan
View Affiliations

Affiliations: Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: May 7, 2020 https://doi.org/10.3892/mmr.2020.11137
Pages: 715-722
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to investigate the effects of human umbilical cord mesenchymal stem cells (Huc‑MSCs)‑derived exosomes on the migratory abilities of endometrial glandular epithelial cells, and to evaluate the underlying mechanism from the perspective of epithelial‑mesenchymal transition (EMT). Huc‑MSCs were prepared from human umbilical cord, and eutopic endometrial glandular epithelial cells were isolated from patients with endometriosis. The exosomes derived from Huc‑MSCs (Huc‑MSCs‑exo) were prepared using an exosome extraction kit. The endometrial glandular epithelial cells were randomly divided into two groups: Huc‑MSCs‑exo and control. Cell migratory ability was assessed and western blotting was used to detect the expression levels of EMT. The results of the present study demonstrated that Huc‑MSCs‑exo treatment significantly enhanced the migration of endometrial glandular epithelial cells from patients with endometriosis (P<0.05). The present study also demonstrated that treatment with Huc‑MSCs‑exo inhibited the expression levels of E‑cadherin and promoted the expression levels of Vimentin and N‑cadherin at both the mRNA and protein level. The results of the current study indicate that Huc‑MSCs‑exo enhance the migratory ability of endometrial glandular epithelial cells via promotion of EMT.

View Figures

View References

1	Vercellini P, Viganò P, Somigliana E and Fedele L: Endometriosis: Pathogenesis and treatment. Nat Rev Endocrinol. 10:261–275. 2014. View Article : Google Scholar : PubMed/NCBI
2	Mehedintu C, Plotogea MN, Ionescu S and Antonovici M: Endometriosis still a challenge. J Med Life. 7:349–357. 2014.PubMed/NCBI
3	Peiris AN, Chaljub E and Medlock D: Endometriosis. JAMA. 320:26082018. View Article : Google Scholar : PubMed/NCBI
4	Berkley KJ, Rapkin AJ and Papka RE: The pains of endometriosis. Science. 308:1587–1589. 2005. View Article : Google Scholar : PubMed/NCBI
5	Matsuzaki S and Darcha C: Co-operation between the AKT and ERK signaling pathways may support growth of deep endometriosis in a fibrotic microenvironment in vitro. Hum Reprod. 30:1606–1616. 2015. View Article : Google Scholar : PubMed/NCBI
6	Orbay H, Tobita M and Mizuno H: Mesenchymal stem cells isolated from adipose and other tissues: Basic biological properties and clinical applications. Stem Cells Int. 2012:4617182012. View Article : Google Scholar : PubMed/NCBI
7	Li X, Wang Q, Ding L, Wang YX, Zhao ZD, Mao N, Wu CT, Wang H, Zhu H and Ning SB: Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens. Stem Cell Res Ther. 10:2672019. View Article : Google Scholar : PubMed/NCBI
8	Samanta S, Rajasingh S, Drosos N, Zhou Z, Dawn B and Rajasingh J: Exosomes: New molecular targets of diseases. Acta Pharmacol Sin. 39:501–513. 2018. View Article : Google Scholar : PubMed/NCBI
9	Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Wang M, Zhou Y, Zhu W, Li W and Xu W: Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev. 22:845–854. 2013. View Article : Google Scholar : PubMed/NCBI
10	Jiang L, Zhang S, Hu H, Yang J, Wang X, Ma Y, Jiang J, Wang J, Zhong L, Chen M, et al: Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages. Biochem Biophys Res Commun. 508:735–741. 2019. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Hao Z, Wang P, Xia Y, Wu J, Xia D, Fang S and Xu S: Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture. Cell Prolif. 52:e125702019. View Article : Google Scholar : PubMed/NCBI
12	Pastushenko I, Brisebarre A, Sifrim A, Fioramonti M, Revenco T, Boumahdi S, Van Keymeulen A, Brown D, Moers V, Lemaire S, et al: Identification of the tumour transition states occurring during EMT. Nature. 556:463–468. 2018. View Article : Google Scholar : PubMed/NCBI
13	Barriere G, Fici P, Gallerani G, Fabbri F and Rigaud M: Epithelial mesenchymal transition: A double-edged sword. Clin Transl Med. 4:142015. View Article : Google Scholar : PubMed/NCBI
14	Liang H, Yu T, Han Y, Jiang H, Wang C, You T, Zhao X, Shan H, Yang R, Yang L, et al: LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression. Mol Cancer. 17:1192018. View Article : Google Scholar : PubMed/NCBI
15	Son H and Moon A: Epithelial-mesenchymal transition and cell invasion. Toxicol Res. 26:245–252. 2010. View Article : Google Scholar : PubMed/NCBI
16	GBD 2015 Disease and Injury Incidence and Prevalence Collaborators, . Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the global burden of disease study 2015. Lancet. 388:1545–1602. 2016. View Article : Google Scholar : PubMed/NCBI
17	Mboi N, Murty Surbakti I, Trihandini I, Elyazar I, Houston Smith K, Bahjuri Ali P, Kosen S, Flemons K, Ray SE, Cao J, et al: On the road to universal health care in Indonesia, 1990–2016: A systematic analysis for the global burden of disease study 2016. Lancet. 392:581–591. 2018. View Article : Google Scholar : PubMed/NCBI
18	Marrazzo P, Crupi AN, Alviano F, Teodori L and Bonsi L: Exploring the roles of MSCs in infections: Focus on bacterial diseases. J Mol Med (Berl). 97:437–450. 2019. View Article : Google Scholar : PubMed/NCBI
19	Droujinine IA, Eckert MA and Zhao W: To grab the stroma by the horns: From biology to cancer therapy with mesenchymal stem cells. Oncotarget. 4:651–664. 2013. View Article : Google Scholar : PubMed/NCBI
20	Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A, Battula VL, Weil M, Andreeff M and Marini FC: Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells. 27:2614–2623. 2009. View Article : Google Scholar : PubMed/NCBI
21	Klopp AH, Gupta A, Spaeth E, Andreeff M and Marini F III: Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells. 29:11–19. 2011. View Article : Google Scholar : PubMed/NCBI
22	Rhee KJ, Lee JI and Eom YW: Mesenchymal stem cell-mediated effects of tumor support or suppression. Int J Mol Sci. 16:30015–30033. 2015. View Article : Google Scholar : PubMed/NCBI
23	Zhao X, Wu X, Qian M, Song Y, Wu D and Zhang W: Knockdown of TGF-β1 expression in human umbilical cord mesenchymal stem cells reverts their exosome-mediated EMT promoting effect on lung cancer cells. Cancer Lett. 428:34–44. 2018. View Article : Google Scholar : PubMed/NCBI
24	Cocucci E, Racchetti G and Meldolesi J: Shedding microvesicles: Artefacts no more. Trends Cell Biol. 19:43–51. 2009. View Article : Google Scholar : PubMed/NCBI
25	Schneider A and Simons M: Exosomes: Vesicular carriers for intercellular communication in neurodegenerative disorders. Cell Tissue Res. 352:33–47. 2013. View Article : Google Scholar : PubMed/NCBI
26	Herrera MB, Fonsato V, Gatti S, Deregibus MC, Sordi A, Cantarella D, Calogero R, Bussolati B, Tetta C and Camussi G: Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med. 14:1605–1618. 2010. View Article : Google Scholar : PubMed/NCBI
27	Mokarizadeh A, Delirezh N, Morshedi A, Mosayebi G, Farshid AA and Mardani K: Microvesicles derived from mesenchymal stem cells: Potent organelles for induction of tolerogenic signaling. Immunol Lett. 147:47–54. 2012. View Article : Google Scholar : PubMed/NCBI
28	Pakravan K, Babashah S, Sadeghizadeh M, Mowla SJ, Mossahebi-Mohammadi M, Ataei F, Dana N and Javan M: MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. Cell Oncol (Dordr). 40:457–470. 2017. View Article : Google Scholar : PubMed/NCBI
29	Ono M, Kosaka N, Tominaga N, Yoshioka Y, Takeshita F, Takahashi RU, Yoshida M, Tsuda H, Tamura K and Ochiya T: Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal. 7:ra632014. View Article : Google Scholar : PubMed/NCBI
30	Reza AMMT, Choi YJ, Yasuda H and Kim JH: Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells. Sci Rep. 6:384982016. View Article : Google Scholar : PubMed/NCBI
31	Ko SF, Yip HK, Zhen YY, Lee CC, Lee CC, Huang CC, Ng SH and Lin JW: Adipose-derived mesenchymal stem cell exosomes suppress hepatocellular carcinoma growth in a rat model: Apparent diffusion coefficient, natural killer T-cell responses, and histopathological features. Stem Cells Int. 2015:8535062015. View Article : Google Scholar : PubMed/NCBI
32	Wang J, Hendrix A, Hernot S, Lemaire M, De Bruyne E, Van Valckenborgh E, Lahoutte T, De Wever O, Vanderkerken K and Menu E: Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood. 124:555–566. 2014. View Article : Google Scholar : PubMed/NCBI
33	Gu H, Ji R, Zhang X, Wang M, Zhu W, Qian H, Chen Y, Jiang P and Xu W: Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway. Mol Med Rep. 14:3452–3458. 2016. View Article : Google Scholar : PubMed/NCBI
34	Ji R, Zhang B, Zhang X, Xue J, Yuan X, Yan Y, Wang M, Zhu W, Qian H and Xu W: Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer. Cell Cycle. 14:2473–2483. 2015. View Article : Google Scholar : PubMed/NCBI
35	Qi J, Zhou Y, Jiao Z, Wang X, Zhao Y and Li Y, Chen H, Yang L, Zhu H and Li Y: Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth through hedgehog signaling pathway. Cell Physiol Biochem. 42:2242–2254. 2017. View Article : Google Scholar : PubMed/NCBI
36	Shi S, Zhang Q, Xia Y, You B, Shan Y, Bao L, Li L, You Y and Gu Z: Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression. Am J Cancer Res. 6:459–472. 2016.PubMed/NCBI
37	Polyak K and Weinberg RA: Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits. Nat Rev Cancer. 9:265–273. 2009. View Article : Google Scholar : PubMed/NCBI
38	Acloque H, Adams MS, Fishwick K, Bronner-Fraser M and Nieto MA: Epithelial-mesenchymal transitions: The importance of changing cell state in development and disease. J Clin Invest. 119:1438–1449. 2009. View Article : Google Scholar : PubMed/NCBI
39	Zhu W, Huang L, Li Y, Qian H, Shan X, Yan Y, Mao F, Wu X and Xu WR: Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth. Cell Cycle. 10:3198–3207. 2011. View Article : Google Scholar : PubMed/NCBI
40	Zhu W, Huang L, Li Y, Zhang X, Gu J, Yan Y, Xu X, Wang M, Qian H and Xu W: Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 315:28–37. 2012. View Article : Google Scholar : PubMed/NCBI
41	Bartley J, Jülicher A, Hotz B, Mechsner S and Hotz H: Epithelial to mesenchymal transition (EMT) seems to be regulated differently in endometriosis and the endometrium. Arch Gynecol Obstet. 289:871–881. 2014. View Article : Google Scholar : PubMed/NCBI
42	Loh CY, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, Chong PP and Looi CY: The E-cadherin and N-cadherin switch in epithelial-to-mesenchymal transition: Signaling, therapeutic implications, and challenges. Cells. 8(pii): E11182019. View Article : Google Scholar : PubMed/NCBI