Magnetic Nanoparticle-Based Upregulation of B-Cell Lymphoma 2 Enhances Bone Regeneration.
Magnetic Nanoparticle-Based Upregulation of B-Cell Lymphoma 2 Enhances Bone Regeneration.
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DOI：
10.5966/sctm.2016-0051
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发表时间：
2017-01
影响因子：
6
通讯作者：
Wan DC
中科院分区：
文献类型：
--
作者：
Brett E;Zielins ER;Luan A;Ooi CC;Shailendra S;Atashroo D;Menon S;Blackshear C;Flacco J;Quarto N;Wang SX;Longaker MT;Wan DC
基于细胞的组织再生策略的临床转化仍然具有挑战性，因为植入细胞在恶劣的缺氧伤口环境中的存活是不确定的。B-细胞淋巴瘤2（Bcl-2）的过表达已被证明可抑制植入细胞的凋亡。本研究描述了一种与磁性纳米颗粒（MNP）集成的“现成”预制支架，用于上调植入的脂肪源性基质细胞中Bcl-2的表达，用于骨再生。氧化铁核依次用支链聚乙烯亚胺、编码绿色荧光蛋白和Bcl-2的小环质粒和聚β-氨基酯包被。通过体外试验，磁转染组的成骨潜力和生物弹性比对照组和核转染组增加。同样，我们的体内颅骨缺损研究表明，磁转染的有效率为30%，这反过来又导致与对照组和核转染组相比显著更多的愈合。我们的新型预制MNP整合支架允许原位植入后时空控制细胞转染以增强骨再生。干细胞转化医学2017;6：151-160
Clinical translation of cell‐based strategies for tissue regeneration remains challenging because survival of implanted cells within hostile, hypoxic wound environments is uncertain. Overexpression of B‐cell lymphoma 2 (Bcl‐2) has been shown to inhibit apoptosis in implanted cells. The present study describes an “off the shelf” prefabricated scaffold integrated with magnetic nanoparticles (MNPs) used to upregulate Bcl‐2 expression in implanted adipose‐derived stromal cells for bone regeneration. Iron oxide cores were sequentially coated with branched polyethyleneimine, minicircle plasmid encoding green fluorescent protein and Bcl‐2, and poly‐β‐amino ester. Through in vitro assays, increased osteogenic potential and biological resilience were demonstrated in the magnetofected group over control and nucleofected groups. Similarly, our in vivo calvarial defect study showed that magnetofection had an efficiency rate of 30%, which in turn resulted in significantly more healing compared with control group and nucleofected group. Our novel, prefabricated MNP‐integrated scaffold allows for in situ postimplant temporospatial control of cell transfection to augment bone regeneration. Stem Cells Translational Medicine 2017;6:151–160