Zhao Jingyuan, Guan Xin, Liu Yang, Piao Hua, Liu Rutao, Zhou Xiang, Sun Bo, Du Yue, Liu Jing
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China.
College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Cell Biol Int. 2017 Apr;41(4):423-432. doi: 10.1002/cbin.10737. Epub 2017 Feb 20.
Cell labeling and tracing have played an increasingly important role in the field of stem cell transplantation. Nanocomplexes combining three Food and Drug Administration (FDA)-approved drugs: heparin (H), protamine (P), and ferumoxytol (F) (HPF nanocomplexes) display high labeling efficiency in human adipose tissue-derived stem cells (hADSCs), but their biological safety has not been determined. In this study, we tested the labeling efficiency of HPF in hADSCs through in vitro cytotoxicity studies and in vivo murine preclinical studies using HPF-labeled hADSCs. The labeling process did not cause cell apoptosis and had little effect on cell proliferation. In vivo magnetic resonance imaging (MRI) showed that the HPF-labeled cells produced a hypointense signal that did not affect liver and kidney functions. However, after injection of HPF-labeled cells into mice, lymphocyte transformation testing showed that T and B lymphocyte proliferation was significantly increased. These findings suggest that extensive safety testing of HPF nanocomplexes is necessary; the process to evaluate HPF as an investigative new drug application could therefore be postponed.
细胞标记和追踪在干细胞移植领域发挥着越来越重要的作用。由三种美国食品药品监督管理局（FDA）批准的药物——肝素（H）、鱼精蛋白（P）和铁羧麦芽糖（F）组成的纳米复合物（HPF纳米复合物）在人脂肪组织来源的干细胞（hADSCs）中显示出高标记效率，但其生物安全性尚未确定。在本研究中，我们通过体外细胞毒性研究以及使用HPF标记的hADSCs进行的体内小鼠临床前研究，测试了HPF在hADSCs中的标记效率。标记过程未导致细胞凋亡，对细胞增殖影响很小。体内磁共振成像（MRI）显示，HPF标记的细胞产生低信号，且不影响肝肾功能。然而，将HPF标记的细胞注射到小鼠体内后，淋巴细胞转化试验表明T和B淋巴细胞增殖显著增加。这些发现表明，对HPF纳米复合物进行广泛的安全性测试是必要的；因此，将HPF评估为研究性新药的申请过程可能会推迟。
