Effect of deforolimus and VEGF on angiogenesis in endometrial stromal cells following three-dimensional culture


The presence of endometrial tissue outside of the uterine cavity is named endometriosis and is the most common gynecologic disorder in women. Determining the inhibitory effect of a Deforolimus on angiogenesis in a three-dimensional (3-D) culture of human endometrial stromal cells (hEnCs) in vitro. The important mechanism in the pathogenesis of endometriosis is angiogenesis, and deforolimus has been shown to have anti-angiogenic activity. This was an in vitro study of human endometrial stromal cells in 3-D culture of fibrin matrix. Endometrial stromal cells isolated and placed in a 3-D fibrin matrix culture system for angiogenesis with VEGF and inhibit angiogenesis by deforolimus. Finally these cells analyzed by CD31 antibodies. After 3 weeks, in cells treated with VEGF, endothelial cell branching was observed and rudimentary capillary-like structures formed. In the presence of 5μM of deforolimus, angiogenesis was reduced. The deforolimus were shown to be effective in inhibiting the mechanisms of angiogenesis.

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Ai, J. , Ebrahimi, S. , Ai, A. , Karimi, R. and Bahrami, N. (2013) Effect of deforolimus and VEGF on angiogenesis in endometrial stromal cells following three-dimensional culture. Stem Cell Discovery, 3, 7-12. doi: 10.4236/scd.2013.31002.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Kettel, L.M. and Hummel, W.P. (1997) Modern medical management of endometriosis. Obstetrics and Gynecology Clinics of North America, 24, 361-367. doi:10.1016/S0889-8545(05)70309-0
[2] Adamson, G.D. and Nelson, H.P. (1997) Surgical treatment of endometriosis. Obstetrics and Gynecology Clinics of North America, 24, 375-409. doi:10.1016/S0889-8545(05)70310-7
[3] Norrby, K. (1997) Angiogenesis—New aspects relating to its initiation and control. Acta Pathologica, Microbiologica et Immunologica Scandinavica, 105, 417-437. doi:10.1111/j.1699-0463.1997.tb00590.x
[4] Healy, D.L., Rogers, P.A.W., Hii, L. and Wingfield, M. (1998) Angiongenesis: A new theory for endometriosis. Human Reproductive Update, l4, 736-740. doi:10.1093/humupd/4.5.736
[5] Kim, S.U. and Vellis, J. (2009) Stem cell based cell therapy in neurological diseases: A review. Journal of Neuroscience Research, 87, 2183-2200. doi:10.1002/jnr.22054
[6] Pucéat, M. (2006) Stem cell therapy in heart failure: Where do we stand and where are we heading? Heart Failure Monitor, 5, 44-49.
[7] Gargett, C.E., Schwab, K.E., Zillwood, R.M., Nguyen, H.P.T. and Wu, D. (2009) Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biology Reproduction, 80, 1136-1145. doi:10.1095/biolreprod.108.075226
[8] Meng, X., Ichim, T. and Zhong, J. (2007) Endometrial regenerative cells: A novel stem cell population. Journal of Translational Medicine, 5, 57-63. doi:10.1186/1479-5876-5-57
[9] Esfandiari, N., Ai, J., Bielecki, R., Gotlieb, L. and Casper, R.F. (2007) Expression of glycodelin and cyclooxygenase-2 in human endometrial tissue following three-dimensional culture. American Journal of Reproductive Immunology, 57, 49-54. doi:10.1111/j.1600-0897.2006.00445.x
[10] Esfandiari, N., Khazaei, M., Ai, J., Bielecki, R., Gotlieb, L. and Ryan, E. (2007) Effect of a statin on an in vitro model of endometriosis. Fertility and Sterility, 87, 257-262. doi:10.1016/j.fertnstert.2006.06.040
[11] Esfandiari, N., Khazaei, M., Ai, J., Nazemian, Z., Jolly, A. and Casper, R. (2008) Angiogenesis following three-dimensional culture of isolated human endometrial stromal cells. International Journal of Fertility Sterility, 2, 19-22.
[12] Taylor, R.N., Lundeen, S.G. and Giudice, L.C. (2002) Emerging role of genomics in endometriosis research. Fertility and Sterility, 78, 694-698. doi:10.1016/S0015-0282(02)03325-3
[13] Figueira, P.G., Abr?o, M., Krikun, G. and Taylor, H.S. (2011) Stem cells in endometrium and their role in the pathogenesis of endometriosis. Annals of the New York Academy of Sciences, 1221, 10-17. doi:10.1111/j.1749-6632.2011.05969.x
[14] Sasson, I.E. and Taylor, H.S. (2008) Stem cells and the pathogenesis of endometriosis. Annals of the New York Academy of Sciences, 1, 106-115. doi:10.1196/annals.1434.014
[15] McGurl, D. (2005) From easter island soil to treating sarcoma rapamycin derivatives. ESUN, 2, 14-19.
[16] Schieke, S.M., Phillips, D., McCoy, J.P., Aponte, A.M., Shen, R.F., Balaban, R.S. and Finkel, T. (2006) The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. Journal of Biological Chemistry, 281, 27643-27652. doi:10.1074/jbc.M603536200
[17] Vignot, S., Faivre, S., Aguirre, D. and Raymond, E. (2005) mTOR-targeted therapy of cancer with rapamycin derivatives. Annals Oncology, 16, 525-537. doi:10.1093/annonc/mdi113
[18] Guba, M., Breitenbuch, P., Steinbauer, M., Koehl, G., Flegel, S. and Hornung, M. (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: Involvement of vascular endothelial growth factor. National Medicine, 8, 128-135. doi:10.1038/nm0202-128
[19] DuBois, S., Marina, N. and Glade-Bender, J. (2010) Angiogenesis and vascular targeting in ewing sarcoma: A review of preclinical and clinical data. Cancer, 116, 749-757. doi:10.1002/cncr.24844
[20] Mobarakeh, T.Z., Ai, J., Yazdani, F., Rezayat, M., Ghanbari, Z., NorooziJavidan A., Massumi, M. and Ebrahmi, S. (2012) Human endometrial stem cells as a new source for programming to neural cells. Cell Biology International Report, 19, 7-14. doi:10.1042/CBR20110009
[21] Folkman, J. (2006) Antiangiogenesis in cancer therapy endostatin and its mechanisms of action. Experimental Cell Research, 312, 594-601. doi:10.1016/j.yexcr.2005.11.015
[22] Ai, J. and Mehrabani, D. (2010) Are endometrial stem cells novel tools against ischemic heart failure in women? A hypothesis. Iran Red Crescent Medicine Journal, 12, 73-75.
[23] Metcalf, C.A., Bohacek, R., Rozamus, L.W., Burns, K.D., Roses, J.B. and Rivera, V.M. (2004) Structure-based design of AP23573, a phosphorous-containing analog of rapamycin for anti-tumor therapy. Cancer Research, 45, 2476-2480
[24] Clackson, T., Metcalf, C.A., Rivera, V.M., Knowles, H.L., Tang, H. and Burns, K.D. (2003) Broad anti-tumor activity of ap23573, an mTOR inhibitor in clinical development. American Society of Clinical Oncology, 22, 882.
[25] Rivera, V.M., Kreisberg, J.I., Mita, M.M., Goldston, M., Knowles, H.L. and Herson, J. (2005) Pharmacodynamic study of skin biopsy specimens in patients (patients) with refractory or advanced malignancies following administration of AP23573, an mTOR inhibitor. American Society of Clinical Oncology, 23, 3033.
[26] Ai, J., Esfandiari, N. and Casper, R. (2009) Detection of aromatase in human endometrial tissue cultured in three-dimensional fibrin matrix in vitro. Iranian Journal of Reproductive Medicine, 7, 105-109.
[27] Ai, J., Noroozi, A. and Mehrabani, D. (2010) The possibility of differentiation of human endometrial stem cells into neural cells. Iranian Journal of Reproductive Medicine, 12, 328-331.
[28] Ai, J., et al. (2012) Derivation of adipocytes from human endometrial stem cells (EnSCs). Journal of Reproduction and Infertility, 13, 151-157.
[29] Ai, J. and Mehrabani, D. (2010) The potential of human endometrial stem cells for osteoblast differentiation. Iranian Journal of Reproductive Medicine, 12, 585-587.
[30] Ai, J., Tabatabaei, F.S. and Kajbafzadeh, A.M. (2009) Myogenic potential of human endometrial adult stem cells. Iranian Journal of Medical Hypotheses and Ideas, 3, 3-6.

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