Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Marchioninistr. 15, 81377 Munich, Germany.
Departments of Orthopedics, Zhongnan Hospital of Wuhan University, 430072 Wuhan, China.
Int J Mol Sci. 2022 Feb 28;23(5):2712. doi: 10.3390/ijms23052712.
Human adipose-derived stem cells (hADSCs) have the capacity for osteogenic differentiation and, in combination with suitable biomaterials and growth factors, the regeneration of bone defects. In order to differentiate hADSCs into the osteogenic lineage, bone morphogenetic proteins (BMPs) have been proven to be highly effective, especially when expressed locally by route of gene transfer, providing a constant stimulus over an extended period of time. However, the creation of genetically modified hADSCs is laborious and time-consuming, which hinders clinical translation of the approach. Instead, expedited single-surgery gene therapy strategies must be developed. Therefore, in an in vitro experiment, we evaluated a novel growth factor delivery system, comprising adenoviral BMP-2 transduced fascia tissue in terms of BMP-2 release kinetics and osteogenic effects, on hADSCs seeded on an innovative biomimetic spongiosa-like scaffold. As compared to direct BMP-2 transduction of hADSCs or addition of recombinant BMP-2, overexpressing fascia provided a more uniform, constant level of BMP-2 over 30 days. Despite considerably higher BMP-2 peak levels in the comparison groups, delivery by overexpressing fascia led to a strong osteogenic response of hADSCs. The use of BMP-2 transduced fascia in combination with hADSCs may evolve into an expedited single-surgery gene transfer approach to bone repair.
人脂肪来源的干细胞(hADSCs)具有成骨分化的能力,并且与合适的生物材料和生长因子结合,能够再生骨缺损。为了将 hADSCs 分化为成骨谱系,骨形态发生蛋白(BMPs)已被证明具有很高的有效性,尤其是通过基因转移途径局部表达时,可在较长时间内提供持续的刺激。然而,构建基因修饰的 hADSCs 既费力又耗时,这阻碍了该方法的临床转化。相反,必须开发加速的单手术基因治疗策略。因此,在一项体外实验中,我们评估了一种新型生长因子递送系统,该系统由腺病毒转导的筋膜组织中的 BMP-2 组成,就 hADSCs 接种在创新的仿生类海绵骨支架上的 BMP-2 释放动力学和成骨效果而言。与 hADSCs 的直接 BMP-2 转导或添加重组 BMP-2 相比,过表达筋膜可在 30 天内提供更均匀、持续的 BMP-2 水平。尽管比较组中的 BMP-2 峰值水平明显更高,但过表达筋膜的递送导致 hADSCs 强烈的成骨反应。将转导 BMP-2 的筋膜与 hADSCs 一起使用,可能会发展成为一种加速的单手术基因转移方法,用于骨修复。