Abd-Allah Somia H, Shalaby Sally M, Abd-Elbary Eman, Saleh Ayman A, El-Magd Mohammed Abu
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Cytotherapy. 2015 Apr;17(4):443-53. doi: 10.1016/j.jcyt.2014.11.002. Epub 2014 Dec 20.
Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury (ALI). In this study, we evaluated the therapeutic effect of isolated human peripheral blood CD34+ progenitor cells in an ALI rat model, induced by oleic acid (OA) injection.
Seventy-five adult female rats were used in this study. Group A, control without treatment, and group B, control injected with phosphate-buffered saline, comprised 15 rats each; the remaining 45 rats were injected with OA to induce ALI and were further subdivided into 3 groups: group C (ALI group, 15 rats), group D (ALI and fibroblast group, 15 rats) and group E (ALI and CD34+ cell group, 15 rats).
CD34+ cells transplantation in rats with OA-induced lung injury improves the arterial PaO(2) and wet/dry ratio, reduces infiltration of inflammatory cells and decreases lung vascular permeability as determined by reduced intra-alveolar and interstitial patchy congestion and hemorrhage as well as decreased interstitial edema. Additionally, lung inflammation determined by expression of the pro-inflammatory mediators intercellular adhesion molecule 1 and tumor necrosis factor-α was attenuated in CD34+ cell-treated rats at 6, 24 and 48 h post-OA challenge compared with non-treated rats. Moreover, the expression of anti-inflammatory molecule interleukin-10 was up-regulated in the lung of OA-induced ALI rats after administration of CD34+ cells. The important finding was that human TNF-α-induced protein 6 (TSG-6) gene expression was significantly up-regulated in rats treated with CD34+ cells.
The freshly isolated human peripheral blood-derived CD34+ cells may be used as an important source of stem cells that improve ALI. The anti-inflammatory properties of CD34+ cells in the lung are explained, at least in part, by activation of CD34+ cells to express TSG-6.
基于成体干细胞的疗法是治疗急性肺损伤（ALI）的一种有前景的新方法。在本研究中，我们评估了分离的人外周血CD34⁺祖细胞在油酸（OA）注射诱导的ALI大鼠模型中的治疗效果。
本研究使用了75只成年雌性大鼠。A组为未治疗的对照组，B组为注射磷酸盐缓冲盐水的对照组，每组各15只大鼠；其余45只大鼠注射OA诱导ALI，并进一步分为3组：C组（ALI组，15只大鼠）、D组（ALI和成纤维细胞组，15只大鼠）和E组（ALI和CD34⁺细胞组，15只大鼠）。
在OA诱导的肺损伤大鼠中移植CD34⁺细胞可改善动脉血氧分压（PaO₂）和湿/干比，减少炎性细胞浸润，并降低肺血管通透性，表现为肺泡内和间质斑片状充血及出血减少以及间质水肿减轻。此外，与未治疗的大鼠相比，在OA攻击后6、24和48小时，经CD34⁺细胞治疗的大鼠中，由促炎介质细胞间黏附分子1和肿瘤坏死因子-α表达所确定的肺部炎症有所减轻。此外，在给予CD34⁺细胞后，OA诱导的ALI大鼠肺中抗炎分子白细胞介素-10的表达上调。重要的发现是，在接受CD34⁺细胞治疗的大鼠中，人肿瘤坏死因子-α诱导蛋白6（TSG-6）基因表达显著上调。
新鲜分离的人外周血来源的CD34⁺细胞可能作为改善ALI的重要干细胞来源。CD34⁺细胞在肺中的抗炎特性至少部分是由CD34⁺细胞激活以表达TSG-6来解释的。
