Shim Gayong, Im Saewon, Lee Sangbin, Park Joo Yeon, Kim Jinyoung, Jin Hyerim, Lee Soondong, Im Irang, Kim Dae-Duk, Kim Seong Who, Lee Taik Jong, Eom Jin Sup, Yi Tac-Ghee, Song Sun Uk, Byun Youngro, Oh Yu-Kyoung
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Eur J Pharm Biopharm. 2013 Nov;85(3 Pt A):673-81. doi: 10.1016/j.ejpb.2013.05.014. Epub 2013 Jun 5.
To improve the survival of transplanted human adipose-derived stem cells (ADSCs), a liposome preparation containing the apoptosome inhibitor, NS3694, was formulated and co-delivered with ADSCs in fibrin gel scaffolds. Liposomes provided enhanced effect on ADSC proliferation in vitro as compared to free drug. Exposure of ADSCs to liposomal NS3694 for 7 days did not affect the surface marker expression profile. NS3694 encapsulated in negatively charged liposomes composed of phosphatidylcholine, phosphatidylglycerol, and cholesterol was evaluated in vivo following subcutaneous transplantation in mice. Survival of ADSCs co-delivered with liposomal NS3694 was significantly higher than that of untreated ADSCs or ADSCs treated with free NS3694 or empty liposomes. An immunohistochemical analysis revealed a higher number of human nucleus-positive cells after treatment with liposomal NS3694 than following treatment with free NS3694. Similarly, liposomal NS3694 significantly enhanced survival of transplanted ADSCs in rabbits compared to other treatments. Taken together, our results indicate the potential of liposomal NS3694 co-delivered with ADSCs using fibrin gel systems as an in vivo-survival enhancer.
为提高移植的人脂肪来源干细胞（ADSCs）的存活率，制备了一种含有凋亡小体抑制剂NS3694的脂质体制剂，并将其与ADSCs一起在纤维蛋白凝胶支架中共同递送。与游离药物相比，脂质体在体外对ADSCs增殖具有增强作用。将ADSCs暴露于脂质体包裹的NS3694 7天不影响其表面标志物表达谱。对由磷脂酰胆碱、磷脂酰甘油和胆固醇组成的带负电荷脂质体包裹的NS3694进行了小鼠皮下移植后的体内评估。与脂质体NS3694共同递送的ADSCs的存活率显著高于未处理的ADSCs、用游离NS3694处理的ADSCs或空脂质体处理的ADSCs。免疫组织化学分析显示，脂质体NS3694处理后人类细胞核阳性细胞数量高于游离NS3694处理后。同样，与其他处理相比，脂质体NS3694显著提高了兔体内移植ADSCs的存活率。综上所述，我们的结果表明，使用纤维蛋白凝胶系统与ADSCs共同递送脂质体NS3694作为体内存活增强剂具有潜力。
