Toward Microsurgical Correction of Cleft Lip Ex Utero through Restoration of Craniofacial Developmental Programs.
Toward Microsurgical Correction of Cleft Lip Ex Utero through Restoration of Craniofacial Developmental Programs.
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通过恢复颅面发育程序来实现宫外唇裂的显微外科矫正。
DOI：
10.1097/prs.0000000000003417
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发表时间：
2017
影响因子：
3.6
通讯作者：
Spector,JasonA
中科院分区：
文献类型：
--
作者：
Dong,Xue;Landford,WilminaN;Hart,James;Risolino,Maurizio;Kaymakcalan,Omer;Jin,Julia;Toyoda,Yoshiko;Ferretti,Elisabetta;Selleri,Licia;Spector,JasonA
背景：伴有或不伴有腭裂的唇裂约占活产儿的五分之一，是最常见的先天性颅面畸形。此前，作者开发了一种具有复合 Pbx 缺陷的独特小鼠模型，该模型表现出完全穿透性唇裂，伴或不伴腭裂。为了探讨妊娠早期组织修复的可能性，作者设计了一种适合宫内修复的微创手术方法，使用 Wnt9b 浸泡的胶原微球来恢复颅面发育程序，以进行唇裂矫正。方法：制造直径范围为 20 至 50 μm 的胶原微球作为 Wnt9b 的递送载体。在妊娠第 11.5 天，分离出野生型和 Pbx 缺陷型小鼠胚胎。通过显微手术将浸泡在鼠纯化 Wnt9b 蛋白中的微球植入中面部人字形交界处。胚胎在 37°C 改良的全胚胎培养系统中培养。结果：Wnt9b 的靶向释放导致人字形连接处 Wnt 表达增强。通过显微手术植入 Wnt9b 浸泡的微球，27.1% 的 Pbx 缺陷胚胎得到了裂隙矫正。植入胚胎和非植入胚胎之间的裂隙面积比率差异显着（p < 0.05）。 结论：通过显微外科干预和靶向输送 Wnt 蛋白的方法，在作者的小鼠模型中对有或没有腭裂的唇裂进行宫外矫正，是一种创新且有前景的策略。尽管需要进一步完善和优化这项技术来提高疗效，但作者相信，这种方法将为对伴有或不伴有腭裂的唇裂患者进行非常规产前干预开辟新途径，并为其他先天性头颈疾病的产前修复提供未来的方法。
Background:Cleft lip with or without cleft palate is present in approximately one in 500 to 700 live births, representing the most common congenital craniofacial anomaly. Previously, the authors developed a unique murine model with compound Pbx deficiency that exhibits fully penetrant cleft lip with or without cleft palate. To investigate the possibility of tissue repair at an early gestational stage, the authors designed a minimally invasive surgical approach suitable for intrauterine repair using Wnt9b-soaked collagen microspheres to restore craniofacial developmental programs for cleft correction.Methods:Collagen microspheres with diameters ranging from 20 to 50 μm were fabricated to serve as a delivery vehicle for Wnt9b. At gestational day 11.5, wild-type and Pbx-deficient murine embryos were isolated. Microspheres soaked in murine purified Wnt9b protein were microsurgically implanted at the midface lambdoidal junction. Embryos were cultured in a 37 C modified whole-embryo culture system.Results:Targeted release of Wnt9b resulted in augmented Wnt expression at the lambdoidal junction. Microsurgical implantation of Wnt9b-soaked microspheres resulted in cleft correction in 27.1 percent of the Pbx-deficient embryos. The difference in the ratio of the areas of clefting between implanted and nonimplanted embryos was significant (p< 0.05).Conclusions:Ex utero correction of cleft lip with or without cleft palate in the authors’ murine model by means of microsurgical intervention and targeted delivery of Wnt proteins is an innovative and promising strategy. Although further refinement and optimization of this technique will be required to improve efficacy, the authors believe that this approach will open new avenues toward unconventional prenatal interventions for patients with cleft lip with or without cleft palate, and provide future approaches for prenatal repair of other congenital head and neck disorders.