Division of Pediatric Surgery, University of California, Los Angeles, CA 90095-7098, USA.
J Pediatr Surg. 2011 Jun;46(6):1208-13. doi: 10.1016/j.jpedsurg.2011.03.057.
Although adrenal insufficiency can be managed with steroid replacement, transplantation of adrenocortical cells may represent a more definitive therapy.
An adrenal failure model was created by adding stress to mice that underwent staged bilateral adrenalectomy. Murine adrenocortical cells were seeded onto collagen sponges. The grafts were implanted under the renal capsule during the first adrenalectomy. Some mice had an additional graft placed next to the kidney. A contralateral adrenalectomy and a laparotomy were performed 1 week after the first adrenalectomy. Two weeks later, blood was collected for corticosterone measurement; and implants were retrieved for adrenal-specific messenger RNA analysis and histology. Mice that underwent the same procedures but received a graft without cells served as controls.
Control group mortality was 100%. Mice that had only one cell-seeded implant had 42% survival, whereas mice that had 2 cell-seeded implants had 100% survival. Retrieved implants demonstrated viable cells and expression of adrenocortical genes. The plasma corticosterone concentration in animals that survived was similar to that in normal mice.
Cells transplantation restored the adrenocortical function in these mice. Further optimization of this technique could bring a curative therapy to patients with adrenal insufficiency.
尽管肾上腺功能不全可以通过类固醇替代治疗来控制，但肾上腺皮质细胞移植可能代表一种更确切的治疗方法。
通过对接受分期双侧肾上腺切除术的小鼠施加应激，创建了肾上腺衰竭模型。将鼠肾上腺皮质细胞接种到胶原海绵上。在第一次肾上腺切除术期间，将移植物植入肾包膜下。一些小鼠在肾旁额外放置了一个移植物。第一次肾上腺切除术 1 周后进行对侧肾上腺切除术和剖腹术。两周后，采集血液进行皮质酮测量；并取出植入物进行肾上腺特异性信使 RNA 分析和组织学检查。接受相同程序但接受无细胞移植物的小鼠作为对照组。
对照组死亡率为 100%。只有一个细胞接种植入物的小鼠存活率为 42%，而有两个细胞接种植入物的小鼠存活率为 100%。回收的植入物显示有存活的细胞和肾上腺皮质基因的表达。存活动物的血浆皮质酮浓度与正常小鼠相似。
细胞移植恢复了这些小鼠的肾上腺皮质功能。进一步优化这项技术可以为肾上腺功能不全的患者带来一种治愈性治疗方法。
