Lo Wen-Cheng, Chiou Jeng-Fong, Gelovani Juri G, Cheong Mei-Leng, Lee Chi-Ming, Liu Hen-Yu, Wu Chih-Hsiung, Wang Ming-Fu, Lin Che-Tong, Deng Win-Ping
Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
J Nucl Med. 2009 May;50(5):765-73. doi: 10.2967/jnumed.108.057372. Epub 2009 Apr 16.
The aim of this study was to develop a cell-based bone-regeneration approach evaluated by molecular imaging and immunohistochemistry.
Genetically modified NIH3T3 embryonic fibroblasts carrying enhanced green fluorescent protein (NIH3T3-G) were predifferentiated into osteoblastlike cells using platelet-rich plasma (PRP) medium, followed by intraosseous transplantation into ovariectomized senescence-accelerated mouse prone substrain 8 (OVX-SAMP8 mice).
PRP-conditioned NIH3T3-G (PRP/NIH3T3-G) engraftment prevented the development of osteoporosis. Molecular imaging and immunohistochemistry demonstrated the migration of NIH3T3-G cells from the implantation site throughout the skeleton. In situ analyses revealed coexpression of osteopontin and green fluorescent protein in the newly formed bone tissue, demonstrating that the transplant restored the bone trabecular architecture and mineral density in treated OVX-SAMP8 mice. Interestingly, the life span of OVX-SAMP8 mice receiving PRP/NIH3T3-G transplantation was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice.
This unique and yet simple approach could potentially be applied to the treatment of senile postmenopausal osteoporosis and perhaps inborn genetic syndromes associated with accelerated aging, such as Hutchinson-Gilford progeria syndrome, and for the prolongation of life expectancy in general.
本研究的目的是开发一种通过分子成像和免疫组织化学评估的基于细胞的骨再生方法。
携带增强型绿色荧光蛋白的基因改造NIH3T3胚胎成纤维细胞(NIH3T3-G)使用富含血小板血浆(PRP)培养基预分化为成骨样细胞,随后骨内移植到去卵巢的衰老加速小鼠易患亚系8(OVX-SAMP8小鼠)中。
PRP处理的NIH3T3-G(PRP/NIH3T3-G)植入可预防骨质疏松症的发展。分子成像和免疫组织化学显示NIH3T3-G细胞从植入部位迁移至整个骨骼。原位分析显示新形成的骨组织中骨桥蛋白和绿色荧光蛋白共表达,表明移植恢复了治疗的OVX-SAMP8小鼠的骨小梁结构和矿物质密度。有趣的是,接受PRP/NIH3T3-G移植的OVX-SAMP8小鼠的寿命显著延长,与同基因抗衰老小鼠品系相似。
这种独特而简单的方法可能潜在地应用于治疗老年绝经后骨质疏松症,也许还可用于治疗与加速衰老相关的先天性遗传综合征,如哈钦森-吉尔福德早衰综合征,并总体上延长预期寿命。