Zheng Yi, Qin Jinbao, Wang Xin, Peng Zhiyou, Hou Peiyong, Lu Xinwu
Department of General Surgery, The Fourth Affiliated Hospital of Guangxi Medical University, Guangxi.
Department of Vascular Surgery, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University.
Int J Nanomedicine. 2016 Dec 21;12:61-71. doi: 10.2147/IJN.S118328. eCollection 2017.
Transplantation of allogeneic adipose-derived regenerative cells (ADRCs) is a promising treatment modality for severe ischemic diseases. However, minimal information is available on the in vivo effects, fate, and migration of ADRCs, as well as the mechanisms of their therapeutic angiogenesis.
In this study, green fluorescent protein-expressing ADRCs (GFP-ADRCs) were obtained, labeled with acetylated 3-aminopropyltrimethoxysilane (APTS)-coated iron oxide nanoparticles (APTS NPs), and injected into an old apolipoprotein E knockout (ApoE-KO) mouse model with hind limb ischemia. Then, 3.0 T magnetic resonance imaging (MRI) was performed to dynamically trace the role of ADRCs targeting hind limb ischemia in the ApoE-KO mice model.
Labeled cells were visualized as large hypointense spots in ischemic muscles by serial 3.0 T MRI scans during a 4-week follow-up. The presence of labeled GFP-ADRCs was confirmed by Prussian blue staining and fluorescence microscopy on postmortem specimens.
This study showed that allogeneic ADRCs offer great potential application for therapeutic angiogenesis in severe ischemic disease based on the efficacy and feasibility of ADRC transplantation and on the available amounts of tissue.
同种异体脂肪来源的再生细胞(ADRCs)移植是治疗严重缺血性疾病的一种有前景的治疗方式。然而,关于ADRCs的体内效应、命运、迁移以及其治疗性血管生成机制的信息极少。
在本研究中,获取表达绿色荧光蛋白的ADRCs(GFP-ADRCs),用乙酰化3-氨丙基三甲氧基硅烷(APTS)包被的氧化铁纳米颗粒(APTS NPs)进行标记,然后注入患有后肢缺血的老年载脂蛋白E基因敲除(ApoE-KO)小鼠模型中。接着,进行3.0 T磁共振成像(MRI)以动态追踪ADRCs在ApoE-KO小鼠模型中靶向治疗后肢缺血的作用。
在为期4周的随访期间,通过连续的3.0 T MRI扫描,标记细胞在缺血肌肉中呈现为大的低信号斑点。通过对死后标本进行普鲁士蓝染色和荧光显微镜检查,证实了标记的GFP-ADRCs的存在。
基于ADRCs移植的有效性和可行性以及组织的可获取量,本研究表明同种异体ADRCs在严重缺血性疾病的治疗性血管生成方面具有巨大的潜在应用价值。