Madhu Vedavathi, Kilanski Allison, Reghu Nikitha, Dighe Abhijit S, Cui Quanjun
Department of Orthopaedic Surgery, Orthopaedic Research Laboratories, School of Medicine, University of Virginia, Charlottesville, Virginia, 22908.
J Orthop Res. 2015 May;33(5):625-32. doi: 10.1002/jor.22883. Epub 2015 Mar 31.
Adipose-derived stem cells (ADSCs) can be excellent alternative to bone marrow derived stem cells for enhancing fracture repair since ADSCs can be isolated comparatively in large numbers from discarded lipoaspirates. However, osteogenic potential of ADSCs in vivo is very controversial. We hypothesized that adipose-derived stem cells (ADSCs) that respond maximally to bone morphogenetic proteins (BMPs) in vitro would possess maximum bone-forming potential. Four purified populations of mouse ADSCs: CD105(+) CD34(+), CD105(-) CD34(-), CD105(+) CD34(-) and CD105(-) CD34(+) were obtained using fluorescence-activated cell sorting (FACS) and their BMP-responsiveness was determined in vitro. CD105(+) CD34(-) population showed the strongest response to BMPs in terms of robust increase in mineralization. Expression of CD105 correlated with high BMP-responsive phenotype and larger cell size while expression of CD34 correlated with low BMP-responsive phenotype and smaller cell size. CD105(+) CD34(-) population displayed higher gene expression of Alk1 or Alk6 receptors in comparison with other populations. However, CD105(+) CD34(-) ADSCs failed to induce ectopic bone formation in vivo after they were transplanted into syngeneic mice, indicating that in vitro BMP-responsiveness is not a good indicator to predict in vivo bone forming potential of ADSCs. Therefore greater precautions should be executed during selection of competent ADSCs for bone repair.
脂肪来源干细胞（ADSCs）可成为骨髓来源干细胞的优良替代品，用于增强骨折修复，因为ADSCs可从废弃的脂肪抽吸物中相对大量地分离出来。然而，ADSCs在体内的成骨潜能极具争议。我们推测，在体外对骨形态发生蛋白（BMPs）反应最大的脂肪来源干细胞（ADSCs）具有最大的骨形成潜能。使用荧光激活细胞分选（FACS）获得了四个纯化的小鼠ADSCs群体：CD105(+) CD34(+)、CD105(-) CD34(-)、CD105(+) CD34(-)和CD105(-) CD34(+)，并在体外测定了它们对BMP的反应性。就矿化的强劲增加而言，CD105(+) CD34(-)群体对BMPs的反应最强。CD105的表达与高BMP反应性表型和较大细胞大小相关，而CD34的表达与低BMP反应性表型和较小细胞大小相关。与其他群体相比，CD105(+) CD34(-)群体显示出更高的Alk1或Alk6受体基因表达。然而，CD105(+) CD34(-) ADSCs在移植到同基因小鼠体内后未能在体内诱导异位骨形成，这表明体外BMP反应性不是预测ADSCs体内骨形成潜能的良好指标。因此，在选择用于骨修复的合格ADSCs时应格外谨慎。
