生物谷Bioon.com 訊 美國圣弗朗西斯科市加利福尼亞大學(xué)心血管研究所的Michael A.Matthay 和Jae W.Lee博士領(lǐng)導(dǎo)的研究小組在《生物化學(xué)》雜志上發(fā)表論文稱他們的研究證實(shí)來源于病患骨髓的干細(xì)胞有治療急性肺損傷的潛力，并揭示了骨髓干細(xì)胞修復(fù)損傷肺細(xì)胞的機(jī)理,。
“我們發(fā)現(xiàn)這些干細(xì)胞能夠大量分泌一種蛋白,，形成一道屏障阻止液體及其他物質(zhì)進(jìn)入肺泡。”UCSF麻醉系副教授Lee說道：“我們樂觀地認(rèn)為將有希望進(jìn)入到臨床試驗(yàn)中”,。
過去幾十年以來,，科學(xué)家們利用骨髓固有的再生特性治療血液相關(guān)疾病患者，不久前利用骨髓干細(xì)胞修復(fù)損傷組織的研究開始受到關(guān)注,。骨髓中有兩種干細(xì)胞,。一種是造血干細(xì)胞可基于免疫系統(tǒng)的需要生成紅細(xì)胞和白細(xì)胞。Matthay 和 Lee研究的是另一種骨髓干細(xì)胞——間充質(zhì)干細(xì)胞,。雖然間充質(zhì)細(xì)胞也可生成血細(xì)胞,，最令科學(xué)家們感興趣的是它能夠分化為各種成熟細(xì)胞,，形成人體各種組織器官。Lee認(rèn)為在過去的幾年里,，由于干細(xì)胞在基于細(xì)胞治療方面的臨床應(yīng)用,，其生物學(xué)機(jī)理越來越受到大家的關(guān)注。
臨床很多疾病例如肺炎和敗血癥均可引起急性肺損傷,，有時(shí)可發(fā)展為更嚴(yán)重的病癥——急性呼吸窘迫綜合征,，嚴(yán)重的通氣/血流比例失調(diào)最終導(dǎo)致器官衰竭。健康肺組織中的肺泡在呼吸時(shí)吸入氧氣,，呼出二氧化碳,。肺泡上皮細(xì)胞起著重要的屏障作用，保證特異物質(zhì)的進(jìn)出,，維持氣體交換平衡,。炎癥導(dǎo)致的損傷或感染可使肺泡上皮通透性增加，從而肺泡中滲入并積聚大量的致死性物質(zhì)例如液體和細(xì)胞,。盡管急性肺損傷和急性呼吸窘迫綜合征的研究被廣泛開展,，患者的死亡率仍然很高，大約在40%左右,。試驗(yàn)研究中治療肺損傷的藥理學(xué)方法還未有效地運(yùn)用到臨床治療中,。
“當(dāng)前的治療方法主要是支持治療，因此需要引入新的治療方法” 共同作者Arne P. Neyrinck認(rèn)為,。
這個(gè)研究團(tuán)隊(duì)在實(shí)驗(yàn)室構(gòu)建了非健康肺組織模型即通過培育人類肺泡上皮細(xì)胞,，再以化學(xué)方法引起炎癥，進(jìn)而觀察骨髓干細(xì)胞如何改變這種狀況,。“我們導(dǎo)入間充質(zhì)干細(xì)胞,，它產(chǎn)生了大量的血管生成素1（1angiopoietin-1）在炎癥損傷后可抑制肺泡上皮通透性增加。”文章的第一作者說道,。
研究者們認(rèn)為他們的研究第一次證實(shí)了間充質(zhì)干細(xì)胞修復(fù)肺泡上皮細(xì)胞的機(jī)制,，他們期待著臨床試驗(yàn)證實(shí)這種方法可以有效地防治重癥患者呼吸衰竭。（生物谷Bioon.com）
生物谷推薦原文出處：
JBC doi: 10.1074/jbc.M110.119917
Allogeneic Human Mesenchymal Stem Cells Restore Epithelial Protein Permeability in Cultured Human Alveolar Type II Cells by Secretion of Angiopoietin-1*?
Xiaohui Fang?, Arne P. Neyrinck?, Michael A. Matthay?§? and Jae W. Lee??,1
From the ?The Cardiovascular Research Institute, the §Department of Medicine, and the ?Department of Anesthesiology, University of California, San Francisco, California 94143
Acute lung injury is characterized by injury to the lung epithelium that leads to impaired resolution of pulmonary edema and also facilitates accumulation of protein-rich edema fluid and inflammatory cells in the distal airspaces of the lung. Recent in vivo and in vitro studies suggest that mesenchymal stem cells (MSC) may have therapeutic value for the treatment of acute lung injury. Here we tested the ability of human allogeneic mesenchymal stem cells to restore epithelial permeability to protein across primary cultures of polarized human alveolar epithelial type II cells after an inflammatory insult. Alveolar epithelial type II cells were grown on a Transwell plate with an air-liquid interface and injured by cytomix, a combination of IL-1β, TNFα, and IFNγ. Protein permeability measured by 131I-labeled albumin flux was increased by 5-fold over 24 h after cytokine-induced injury. Co-culture of human MSC restored type II cell epithelial permeability to protein to control levels. Using siRNA knockdown of potential paracrine soluble factors, we found that angiopoietin-1 secretion was responsible for this beneficial effect in part by preventing actin stress fiber formation and claudin 18 disorganization through suppression of NFκB activity. This study provides novel evidence for a beneficial effect of MSC on alveolar epithelial permeability to protein.
