Human embryonic stem cells differentiated to lung lineage-specific cells ameliorate pulmonary fibrosis in a xenograft transplant mouse model.
Human embryonic stem cells differentiated to lung lineage-specific cells ameliorate pulmonary fibrosis in a xenograft transplant mouse model.
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DOI：
10.1371/journal.pone.0033165
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Henderson WR Jr
中科院分区：
文献类型：
--
作者：
Banerjee ER;Laflamme MA;Papayannopoulou T;Kahn M;Murry CE;Henderson WR Jr
我们的目的是将人（h）胚胎干（ES）细胞分化为肺上皮谱系特异性细胞[即，肺泡上皮I型（AEI）和II型（AEII）细胞和Clara细胞]作为开发基于细胞的策略以修复特发性肺纤维化（IPF）的博来霉素小鼠模型中的肺损伤的第一步。非纤毛肺谱系特异性细胞的异质群体是通过一种新的胚状体（EB）分化方法获得的。这种分化的人细胞群用于调节移植动物中的促纤维化表型。在分化培养基中省略或包含一种或多种组分使H7 hES细胞分化为不同比例的AEI、AEII和Clara细胞偏斜。ICG-001是Wnt/β-catenin/Creb-结合蛋白（CBP）转录的小分子抑制剂，将分化的ES细胞的标志物表达从AEII样表型改变为主要的AEI样表型。分化的细胞用于博来霉素处理的Rag 2 γC−/−小鼠的异种移植研究。在接受用或不用ICG-001处理的分化ES细胞的移植组的肺中检测到人细胞。在接受生理盐水的博来霉素治疗的小鼠中发现的肺胶原含量增加通过移植从ES细胞分化的肺谱系特异性上皮细胞而显著降低。在移植分化的hES细胞后，在博来霉素处理的小鼠的气道中观察到祖细胞数量的显著增加。这项研究表明，ES细胞为基础的治疗可能是一个强大的新的方法来改善肺纤维化。
Our aim was to differentiate human (h) embryonic stem (ES) cells into lung epithelial lineage-specific cells [i.e., alveolar epithelial type I (AEI) and type II (AEII) cells and Clara cells] as the first step in the development of cell-based strategies to repair lung injury in the bleomycin mouse model of idiopathic pulmonary fibrosis (IPF). A heterogeneous population of non-ciliated lung lineage-specific cells was derived by a novel method of embryoid body (EB) differentiation. This differentiated human cell population was used to modulate the profibrotic phenotype in transplanted animals. Omission or inclusion of one or more components in the differentiation medium skewed differentiation of H7 hES cells into varying proportions of AEI, AEII, and Clara cells. ICG-001, a small molecule inhibitor of Wnt/β-catenin/Creb-binding protein (CBP) transcription, changed marker expression of the differentiated ES cells from an AEII-like phenotype to a predominantly AEI-like phenotype. The differentiated cells were used in xenograft transplantation studies in bleomycin-treated Rag2γC−/− mice. Human cells were detected in lungs of the transplanted groups receiving differentiated ES cells treated with or without ICG-001. The increased lung collagen content found in bleomycin-treated mice receiving saline was significantly reduced by transplantation with the lung-lineage specific epithelial cells differentiated from ES cells. A significant increase in progenitor number was observed in the airways of bleomycin-treated mice after transplantation of differentiated hES cells. This study indicates that ES cell-based therapy may be a powerful novel approach to ameliorate lung fibrosis.
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影响因子：
11.4
作者：
Hecht, A;Vleminckx, K;Kemler, R
通讯作者：
Kemler, R
影响因子：
6
作者：
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通讯作者：
Murry, CE
DOI：
10.1016/j.bbrc.2004.05.048
发表时间：
2004-07-02
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2006.09.117
发表时间：
2006-11-24
影响因子：
3.1
作者：
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通讯作者：
Kobayashi, Masashi