Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Thorac Cardiovasc Surg. 2012 Mar;143(3):711-719.e2. doi: 10.1016/j.jtcvs.2011.09.024. Epub 2011 Oct 27.
It is controversial whether lung regeneration contributes to compensatory lung growth after pulmonary resection in mature individuals. The objectives of this study were to clarify the molecular mechanisms that regulate the process of compensatory lung growth and investigate the influence of transplantation of lung cells enriched in alveolar type II cells on compensatory lung growth.
Serial changes of morphology and gene expression were examined in the remnant right lung after pneumonectomy in adult male Wistar rats. One day after surgery, animals received endotracheal transplants of rat lung cells enriched in alveolar type II cells at a dose of 2.5 × 10(6) cells. Serial morphologic changes were examined in comparison with pneumonectomy alone. Engraftment of lung cells was validated with a sex-mismatch model.
The alveolar density with mean linear intercept was always lower in pneumonectomized rats than in sham surgical controls for 6 months after surgery. Microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially up-regulated and then returned to normal after 1 month. In the pneumonectomized rats with transplantation, the alveolar density was equivalent to that in the sham controls. Engraftment of the transplanted cells from male donors in the alveoli of female recipients was proven by detection of Y-chromosome positive cells and quantified by real-time polymerase chain reaction for the Sry gene. This occurred in pneumonectomized rats but not in sham controls.
We postulate that lung cell transplantation stimulates lung regeneration in the remnant lung after pneumonectomy in mature rats.
肺切除后成熟个体的肺再生是否有助于代偿性肺生长存在争议。本研究的目的是阐明调节代偿性肺生长过程的分子机制，并研究富含肺泡 II 型细胞的肺细胞移植对代偿性肺生长的影响。
在成年雄性 Wistar 大鼠肺切除后，检测残肺右肺的形态学和基因表达的连续变化。手术后 1 天，动物接受了 2.5×10（6）个细胞剂量的富含肺泡 II 型细胞的大鼠肺细胞的气管内移植。与单纯肺切除相比，连续观察形态学变化。通过性别错配模型验证肺细胞的植入。
肺切除术后 6 个月，肺切除组的肺泡密度（平均线性截距）始终低于假手术对照组。微阵列分析显示，多个与增殖相关的基因（但与特定的肺泡发育无关）最初上调，1 个月后恢复正常。在移植的肺切除组大鼠中，肺泡密度与假手术对照组相当。通过检测 Y 染色体阳性细胞和实时聚合酶链反应（PCR）定量 Sry 基因，证明了来自雄性供体的移植细胞在雌性受体内的植入。这种情况发生在肺切除组大鼠中，但不在假手术对照组大鼠中发生。
我们推测，肺细胞移植刺激成熟大鼠肺切除后残肺中的肺再生。
