《Nature》最新成果：干细胞移植让受损肺脏再生（附原文）

细胞达人

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《Nature》最新成果：干细胞移植让受损肺脏再生0 |3 ]- t8 P  h+ n. [
来源：生物谷
3 l* H: `% {% K6 t: W来自新加坡基因组研究院和美国杰克逊实验室的左为 (Wei Zuo) 博士、Wa Xian教授和Frank McKeon教授等研究人员开发了一整套革命性的技术，可以分离肺内部存在的少量干细胞，通过体外培养大规模扩增后，重新移植入体内，帮助肺脏的再生。这一重要研究成果近日在线刊登在著名的《自然》（Nature）杂志上。6 v- @1 }6 W  `  `

8 X. m/ E: f' k4 W9 Z& Z' W7 \. A! A) Y% N慢性阻塞性肺病（COPD）和肺纤维化等肺部疾病一直是现代人群的健康杀手。调查表明，中国45岁以上人群，70%以上患有不同程度的慢性肺病。肺部组织结构非常复杂，一旦发生损伤，便很难及时自我修复。因此 肺部疾病大多恶化速度快，且并发症多。而目前除了进行复杂而高风险的全肺移植手术之外，尚缺乏有效的治疗方法。
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有意思的是，一些被流感感染后发生急性呼吸窘迫综合症的病人，他们的肺损伤后能够自我修复再生。本文的研究者在 肺中发现了一种数量稀少的干细胞。这种被称作DASC的干细胞能表达两个特定的基因标记物：p63和Krt5。在流感病毒诱导的小鼠急性呼吸窘迫综合症模型中，内源的DASC干细胞能迅速地扩增并分化成微支气管和肺泡细胞等具有各种功能的细胞，从而重建整个肺的结构。如果用遗传学方法从小鼠中特异性地剔除内源DASC干细胞，小鼠就无法从肺损伤中恢复过来。这说明内源DASC干细胞对于肺脏再生是必需的。# E' e* Y0 s6 _3 |* c+ m

( |" l% W+ [5 l3 b$ w" |利用一种特殊的培养方法，研究者能从小鼠肺中分离到单个的DASC干细胞并在培养皿里进行近乎无限的扩增。当扩增得到的干细胞被移植入另一只小鼠受损的肺里后，研究者们惊奇地发现DASC干细胞能保持持续的活力，并在1到3个月内产生出新的微支气管和肺泡细胞，加速肺脏的再生。这一研究对于急慢性肺部疾病的细胞治疗具有开创性的意义。研究人员表示：目前的研究进展非常激动人心。下一步将会尝试移植人类的DASC干细胞，争取2～3年内进行临床细胞治疗研究，为广大肺病患者带来新的希望。(生物谷Bioon.com): ~+ _! j  K2 B7 L6 J( y' F2 c, e4 a

+ T- ]# u1 G" |$ Sp63+Krt5+ distal airway stem cells are essential for lung regeneration9 q; f+ `- O3 x9 x3 [
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Wei Zuo,         Ting Zhang,         Daniel Zheng'An Wu,         Shou Ping Guan,         Audrey-Ann Liew,         Yusuke Yamamoto,         Xia Wang,         Siew Joo Lim,         Matthew Vincent,         Mark Lessard,         Christopher P. Crum, Wa Xian         & Frank McKeon
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Lung diseases such as chronic obstructive pulmonary disease1 and pulmonary fibrosis2 involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia3, 4 or acute respiratory distress syndrome5, 6 often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASCp63/Krt5, to this process7. Here we show that pre-existing, intrinsically committed DASCp63/Krt5 undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASCp63/Krt5 in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASCp63/Krt5-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases.$ W2 M; a6 p0 X4 x" o) A! y+ e/ Q
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yaolinzhang

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qingxingruyu

有这个肺癌就可以多切点了

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http://www.nature.com/nature/jou ... ll/nature13903.html" i$ {$ N' W3 G, [& @# C) a  P- P+ |

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zhangshich

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yaoguanping

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# Q& E. }. Q9 P9 V% s7 R) f9 LNature：科学家阐明肺脏再生的新机制（半月前已经在本论坛展出）
! t+ }( ~% o- z8 B0 E5 Y此文章可以作为范文来阅读。