美國伊利諾伊大學(xué)醫(yī)學(xué)院的科學(xué)家對患急性肺損傷老鼠模型的研究表明,，成體干細(xì)胞(adult stem cell)能夠治療急性肺損傷(acute lung injury,ALI),。這項研究報告發(fā)表在10月版的Stem Cells雜志上。
急性肺損傷的病理特點為肺泡毛細(xì)血管內(nèi)皮細(xì)胞和肺泡上皮細(xì)胞損傷,，表現(xiàn)為廣泛肺水腫和微小肺不張,。由于內(nèi)皮細(xì)胞生命周期較長，新細(xì)胞的更新需要2～5年時間,，因而在特定時間內(nèi),，用于修復(fù)損傷的干細(xì)胞數(shù)目遠(yuǎn)遠(yuǎn)不夠，并且內(nèi)皮細(xì)胞修復(fù)非常復(fù)雜,。該課題組提出,，干細(xì)胞或許可以用于ALI治療。
Wary及其同事在老鼠骨髓干細(xì)胞中找到了一些祖干細(xì)胞(progenitor stem cells),，因其細(xì)胞表面有Flk-1以及CD34蛋白,，分別將其命名為Flk-1以及CD34。雖然骨髓干細(xì)胞中這類干細(xì)胞的含量極少,，但研究人員還是成功地找到一種增加干細(xì)胞數(shù)量和“粘著度”的細(xì)胞培養(yǎng)方法,。
這些干細(xì)胞可通過細(xì)胞表面的整合素(integrin)黏附到相應(yīng)的靶點并進(jìn)行修復(fù)。研究人員首先對小鼠注射一種物質(zhì)引起小鼠出現(xiàn)急性肺損傷,，然后在注射經(jīng)過培養(yǎng)和純化的Flk-1以及CD34干細(xì)胞,。研究人員發(fā)現(xiàn)，這些祖細(xì)胞能夠修復(fù)肺損傷,，并防止肺部出現(xiàn)積水,。
這項研究證實,，干細(xì)胞療法不僅是一種很有前景的治療ALI的方法，還使研究人員進(jìn)一步了解干細(xì)胞修復(fù)損傷的機制,。（生物谷Bioon.com）
生物谷推薦原始出處：
STEM CELLS DOI:10.1002/stem.241
Requirement of α4β1 and α5β1 Integrin Expression in Bone-Marrow Derived Progenitor Cells in Preventing Endotoxin-Induced Lung Vascular Injury and Edema in Mice
Kishore K. Wary *, Stephen M Vogel, Sean Garrean, Yidan D. Zhao, Asrar B. Malik
Department of Pharmacology and Center for Lung and Vascular Biology, The University of Illinois, Chicago, IL 60612
The goal of this study was to determine the role of integrin-mediated adhesion of bone marrow derived progenitor cells (BMPCs) as a requirement for the endothelial barrier protection in a lung injury model. C57BL mice were used as the source for BMPCs, which were characterized as CD34+ and Flk1+ as well as expression of a repertoire of integrins. We used a mouse model of bacterial lipopolysaccharide (LPS)-induced lung vascular injury and edema formation to test the effects of BMPC integrin expression in preventing endothelial barrier injury. Adhesion of BMPCs to purified extracellular matrix proteins induced Fak phosphorylation and formation of branching point structures in a 4 and 5 integrin-dependent manner. BMPCs expressing red fluorescent protein (RFP) were administered via the retro-orbital venous route in mice treated intraperitonially (i.p.) with LPS [7.5 mg/kg body weight (BW). We observed increased retention of RFP-labeled Flk1+ and CD34+ BMPCs for up to 8 wk in mice injured with LPS. BMPC transplantation increased survival by 50% (at 72 to 96 hr after LPS) and reduced lung vascular injury and extravascular water content induced by LPS. However, blocking with anti-4 or anti-5 integrin antibody, or shRNA mediated silencing of 4 or 5 integrins in donor BMPCs failed to prevent the vascular injury or edema formation and mortality. Thus, 4 and 5 integrin-dependent adhesion of BMPCs in lung tissue plays a critical role in preventing lung vascular injury and increasing survival in a mouse model of LPS-induced acute lung injury.
