Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California 94305-5148, USA.
Stem Cells. 2011 Dec;29(12):2018-29. doi: 10.1002/stem.757.
An urgent need exists in clinical medicine for suitable alternatives to available techniques for bone tissue repair. Human adipose-derived stem cells (hASCs) represent a readily available, autogenous cell source with well-documented in vivo osteogenic potential. In this article, we manipulated Noggin expression levels in hASCs using lentiviral and nonintegrating minicircle short hairpin ribonucleic acid (shRNA) methodologies in vitro and in vivo to enhance hASC osteogenesis. Human ASCs with Noggin knockdown showed significantly increased bone morphogenetic protein (BMP) signaling and osteogenic differentiation both in vitro and in vivo, and when placed onto a BMP-releasing scaffold embedded with lentiviral Noggin shRNA particles, hASCs more rapidly healed mouse calvarial defects. This study therefore suggests that genetic targeting of hASCs combined with custom scaffold design can optimize hASCs for skeletal regenerative medicine.
临床上急需寻找可替代现有骨组织修复技术的方法。人脂肪来源的干细胞（hASCs）是一种易于获得的、自体细胞来源，具有良好的体内成骨潜能。在本文中，我们使用慢病毒和非整合的迷你环短发夹 RNA（shRNA）方法在体外和体内操纵 hASCs 中的 Noggin 表达水平，以增强 hASC 成骨作用。Noggin 敲低的 hASCs 在体外和体内均显示出明显增强的骨形态发生蛋白（BMP）信号和成骨分化，并且当放置在带有慢病毒 Noggin shRNA 颗粒的 BMP 释放支架上时，hASCs 能更快地修复小鼠颅骨缺损。因此，本研究表明，hASC 的基因靶向与定制支架设计相结合可以优化 hASC 用于骨再生医学。
