Collagen-binding basic fibroblast growth factor improves functional remodeling of scarred endometrium in uterine infertile women: a pilot study
- 6 Downloads
Intrauterine adhesion (IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2 (bFGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of bFGF 100 µg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients (2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved. Histological study showed blood vessel density increased obviously. Three patients (3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the bFGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.
Keywordsintrauterine adhesion CBD-bFGF endometrial scarring uterine infertility thin endometrium endometrial reconstruction
Unable to display preview. Download preview PDF.
We thank Yaling Li and her nursing team for assistance in patient care, and thank the patients for their trust and willingness to participate in this clinical trial. This work was supported by The Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030505), Jiangsu Provincial Key Medical Center (YXZXB2016004), Key Research and Development Program of Jiangsu Province (BE2016612), National Natural Science Foundation of China (81771526), Excellent Youth Natural Science Foundation of Jiangsu Province (BK20170051), and Six Talent Peaks Projects in Jiangsu Province (WSW-074).
Compliance and ethicsThe author(s) declare that they have no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of Ethics Committee of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- Eppler, S.M., Combs, D.L., Henry, T.D., Lopez, J.J., Ellis, S.G., Yi, J.H., Annex, B.H., McCluskey, E.R., and Zioncheck, T.F. (2002). A targetmediated model to describe the pharmacokinetics and hemodynamic effects of recombinant human vascular endothelial growth factor in humans. Clin Pharmacol Ther 72, 20–32.CrossRefGoogle Scholar
- Fujita, M., Ishihara, M., Simizu, M., Obara, K., Ishizuka, T., Saito, Y., Yura, H., Morimoto, Y., Takase, B., Matsui, T., et al. (2004). Vascularization in vivo caused by the controlled release of fibroblast growth factor-2 from an injectable chitosan/non-anticoagulant heparin hydrogel. Biomaterials 25, 699–706.CrossRefGoogle Scholar
- Gaudry, M., Bregerie, O., Andrieu, V., El Benna, J., Pocidalo, M.A., and Hakim, J. (1997). Intracellular pool of vascular endothelial growth factor in human neutrophils. Blood 90, 4153–4161.Google Scholar
- Hashimoto, T., Koyama, H., Miyata, T., Hosaka, A., Tabata, Y., Takato, T., and Nagawa, H. (2009). Selective and sustained delivery of basic fibroblast growth factor (bFGF) for treatment of peripheral arterial disease: results of a phase I trial. Eur J Vasc Endovasc Surg 38, 71–75.CrossRefGoogle Scholar
- Jiang, X.W., Zhang, Y., Zhang, H., Lu, K., Yang, S.K., and Sun, G.L. (2013). Double-blind, randomized, controlled clinical trial of the effects of diosmectite and basic fibroblast growth factor paste on the treatment of minor recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Rad 116, 570–575.CrossRefGoogle Scholar
- Kanazawa, T., Komazawa, D., Indo, K., Akagi, Y., Lee, Y., Nakamura, K., Matsushima, K., Kunieda, C., Misawa, K., Nishino, H., et al. (2015). Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis. Laryngoscope 125, E338–E344.CrossRefGoogle Scholar
- Kawaguchi, H., Oka, H., Jingushi, S., Izumi, T., Fukunaga, M., Sato, K., Matsushita, T., Nakamura, K., and Nakamura, K. (2010). A local application of recombinant human fibroblast growth factor 2 for tibial shaft fractures: A randomized, placebo-controlled trial. J Bone Miner Res 25, 2735–2743.CrossRefGoogle Scholar
- Kumagai, M., Marui, A., Tabata, Y., Takeda, T., Yamamoto, M., Yonezawa, A., Tanaka, S., Yanagi, S., Ito-Ihara, T., Ikeda, T., et al. (2016). Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia. Heart Vessels 31, 713–721.CrossRefGoogle Scholar
- Lu, J., Zhu, H., Zhu, X., Tang, X., Wang, H., and Hu, Y. (2017). Logistic regression analysis of the risk factors of severe intrauterine adhesion recurrence (in Chinese). J Pract Obstet Gynecol 33, 751–754.Google Scholar
- Murayama, T., Tepper, O.M., Silver, M., Ma, H., Losordo, D.W., Isner, J. M., Asahara, T., and Kalla, C. (2002). Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 30, 967–972.CrossRefGoogle Scholar
- Shi, C., Chen, W., Zhao, Y., Chen, B., Xiao, Z., Wei, Z., Hou, X., Tang, J., Wang, Z., and Dai, J. (2011). Regeneration of full-thickness abdominal wall defects in rats using collagen scaffolds loaded with collagen-binding basic fibroblast growth factor. Biomaterials 32, 753–759.CrossRefGoogle Scholar
- Shi, Q., Gao, W., Han, X.L., Zhu, X.S., Sun, J., Xie, F., Hou, X.L., Yang, H. L., Dai, J.W., and Chen, L. (2014). Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model. Sci China Life Sci 57, 232–240.CrossRefGoogle Scholar
- Squires, C.H., Childs, J., Eisenberg, S.P., Polverini, P.J., and Sommer, A. (1988). Production and characterization of human basic fibroblast growth factor from Escherichia coli. J Biol Chem 263, 16297–16302.Google Scholar
- Uchi, H., Igarashi, A., Urabe, K., Koga, T., Nakayama, J., Kawamori, R., Tamaki, K., Hirakata, H., Ohura, T., and Furue, M. (2009). Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer. Eur J Dermatol 19, 461–468.Google Scholar
- Wamsteker, K., and De Block, S. (1998). Diagnostic hysteroscopy: Technique and documentation. In Endoscopic Surgery for Gynaecologists. Sutton, C., and Diamond, M., eds. (London: Saunders), pp. 511–524.Google Scholar
- Zhang, D., Huang, Z., Sun, P., Huang, H., Zhang, Y., Dai, J., Liu, J., and Shi, Q. (2017). Acceleration of healing of traumatic tympanic membrane perforation in rats by implanted collagen membrane integrated with collagen-binding basic fibroblast growth factor. Tissue Eng Part A 23, 20–29.CrossRefGoogle Scholar
- Zhao, G., Cao, Y., Zhu, X., Tang, X., Ding, L., Sun, H., Li, J., Li, X., Dai, C., Ru, T., et al. (2017). Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome. Sci China Life Sci 60, 404–416.CrossRefGoogle Scholar
- Zhao, W., Chen, B., Li, X., Lin, H., Sun, W., Zhao, Y., Wang, B., Zhao, Y., Han, Q., and Dai, J. (2007). Vascularization and cellularization of collagen scaffolds incorporated with two different collagen-targeting human basic fibroblast growth factors. J Biomed Mater Res 82A, 630–636.CrossRefGoogle Scholar