Angioi Karine, Hatier Renée, Merle Michel, Duprez Adrien
Experimental Microsurgery Department, Medical School, 9 Ave de la Forêt de Haye BP 184, Vandoeuvre-lès-Nancy Cedex, 54505, France.
J Surg Res. 2002 Feb;102(2):85-94. doi: 10.1006/jsre.2001.6293.
The aim of this study was to study the morphological and functional development in vivo of whole human embryonic and fetal stomachs, intestines, tracheas, and lungs, which would otherwise be ethically and technically impossible to perform in utero, by microsurgically grafting these organs into nude mice.
Five hundred fifty-seven human organs obtained from legally aborted embryos and fetuses of 6-10 weeks were microsurgically grafted into nude mice for 1 to 273 days. Following different grafting times, biopsies were taken for optical and electron microscopy, in situ hybridization, and cellular kinetics studies. A catheter was introduced into the human organs in order to collect and analyze secretions.
All of the grafts took successfully. Macroscopic growth was fast during the first 6 to 10 weeks, following which organ size was stable. In situ hybridization studies detected only a minute level of mouse mesenchymal chimerism in the grafts. The different epithelial cells differentiated, became of adult type, and remained normal during the remainder of the grafting periods. The pH of gastric juice from stomachs grafted for 10 to over 90 days dropped from 8.0 +/- 0.1 to 1.58 +/- 0.29 over this time period (P < 0.001), intrinsic factor levels were stable, and pepsin ranged from 6.8 +/- 7.8 to 134 +/- 51 units (P < 0.001).
These results demonstrate that the development of entoblastic organs from human embryos and fetuses microsurgically grafted into nude mice is similar to that occurring in utero. As such, this method provides a model for the analysis of whole human organs in development and later normal adult-like micro-organs for physiological, therapeutic, and pathological studies.
本研究旨在通过将整个人类胚胎和胎儿的胃、肠、气管及肺显微手术移植到裸鼠体内，研究其在体内的形态和功能发育，否则在子宫内进行此类研究在伦理和技术上是不可能的。
从6至10周合法流产的胚胎和胎儿获取557个人类器官，显微手术移植到裸鼠体内1至273天。在不同移植时间后，取组织进行光学和电子显微镜检查、原位杂交及细胞动力学研究。将导管插入人类器官以收集和分析分泌物。
所有移植均成功。最初6至10周宏观生长迅速，之后器官大小稳定。原位杂交研究在移植组织中仅检测到微量的小鼠间充质嵌合现象。不同上皮细胞分化，变为成人类型，并在移植期剩余时间内保持正常。移植10至90多天的胃所分泌胃液的pH值在此时间段内从8.0±0.1降至1.58±0.29（P<0.001），内因子水平稳定，胃蛋白酶范围为6.8±7.8至134±51单位（P<0.001）。
这些结果表明，显微手术移植到裸鼠体内的人类胚胎和胎儿内胚层器官的发育与子宫内的发育相似。因此，该方法为分析发育中的整个人类器官以及后续用于生理、治疗和病理研究的类似成年微型器官提供了一个模型。
