Transplantation of oral mucosal epithelial cells seeded on decellularized and lyophilized amniotic membrane for the regeneration of injured endometrium
Transplantation of oral mucosal epithelial cells seeded on decellularized and lyophilized amniotic membrane for the regeneration of injured endometrium
复制标题
DOI：
10.1186/s13287-019-1179-z
复制
发表时间：
2019-03-21
影响因子：
7.5
通讯作者：
Bai, Wenpei
中科院分区：
文献类型：
--
作者：
Chen, Xing;Sun, Jingtao;Bai, Wenpei
背景：子宫内膜粘连（IUA）的特征是子宫内膜基底层损伤导致的进行性子宫内纤维化。为了缓解IUA，许多方法已经应用于临床，但效果有限。在本研究中，我们研究了自体口腔黏膜上皮细胞（OMECs）在脱细胞和冻干羊膜（DL-AM）上接种对大鼠IUA模型的预防作用。方法：采用刮取SD大鼠左子宫内膜（右子宫为对照）的方法建立IUA模型。将创面随机分为未修复组（IUA组）、单用DL-AM修复组（DL-AM组）和用DL-AM植入自体OMECs组（DL-AM+OMECs组），共54只大鼠，每只18只。分别于术后3、7、14、28天（每个时间点n=3）采集子宫标本进行组织学和免疫组化评价。结果：术后IUA组和DL-AM组子宫腔内可见广泛纤维化，DL-AM移植组子宫腔内纤维化面积比例较低。CK-18免疫染色显示，经DL-AM接种的OMECs移植可显著减少IUA的纤维化，恢复子宫腔，再生上皮和子宫内膜腺。Ki-67免疫荧光染色显示，OMECs移植导致广泛的细胞增殖。同时，接受OMECs移植的子宫微血管密度显著增加，并伴有血管内皮生长因子的表达升高。妊娠试验（每组n=6）显示omec移植子宫成功受孕，但IUA组和DL-AM组未成功受孕。结论：经OMECs介导的DL-AM培养的工程上皮通过改善子宫内膜上皮再生，在防止宫内粘连进展方面具有很大的潜力。
Background: Intrauterine adhesion (IUA) is characterized by progressive intrauterine fibrosis as a consequence of trauma to the basal layer of the endometrium. In an attempt to relieve IUA, many approaches have been applied in the clinic but show limited effects. In this study, we investigated the effect of autologous oral mucosal epithelial cells (OMECs) seeded on decellularized and lyophilized amniotic membrane (DL-AM) on preventing the development of IUA in a rat model.Methods: IUA model was established by surgical scraping of the endometrium in the left uteri (the right uteri were kept as control) of SD rats. Wounds were randomly treated as unrepaired (IUA group), repaired with DL-AM alone (DL-AM group), and DL-AM seeded with autologous OMECs (DL-AM+OMECs group), respectively, in a total of 54 rats (n=18 each). Uterus samples were harvested for histological and immunohistochemical evaluation after 3, 7, 14, and 28 days (n=3 in each time point) of operations.Results: After surgery, the uterine cavity was observed to be filled with extensive fibrosis in the IUA and DL-AM groups, respectively, while a lower ratio of the fibrotic area was identified in the DL-AM transplantation group. Transplantation of OMECs seeded on DL-AM significantly reduced fibrosis of IUA with recovered uterine cavity and regenerated epithelium and endometrial glands as determined by CK-18 immunostaining. OMECs transplantation resulted in extensive cellular proliferation as revealed by the Ki-67 immunofluorescent staining exhibited. Meanwhile, microvessel density was significantly increased in uteri that received OMECs transplantation, which was concomitant with elevated expression of vascular endothelial growth factor. The pregnancy test (n=6 in each group) showed successful conception in the OMEC-transplanted uteri, but not in the IUA and DL-AM groups.Conclusions: Engineered epithelium developed from DL-AM seeded with OMECs showed great potential in preventing progression of intrauterine adhesion by improved endometrial epithelium regeneration.