Centre for cell Engineering, Institute for Molecular, Cell & Systems Biology, College of Medical, Veterinary & Life Sciencies, University of Glasgow, Glasgow, G12 8QQ, UK.
Nanomedicine (Lond). 2015 Mar;10(4):547-60. doi: 10.2217/nnm.14.134.
Mesenchymal stem cells (MSCs) have large regenerative potential to replace damaged cells from several tissues along the mesodermal lineage. The potency of these cells promises to change the longer term prognosis for many degenerative conditions currently suffered by our aging population. We have endeavored to demonstrate our ability to induce osteoblatogenesis in MSCs using high-frequency (1000-5000 Hz) piezo-driven nanodisplacements (16-30 nm displacements) in a vertical direction.
MATERIALS & METHODS: Osteoblastogenesis has been determined by the upregulation of osteoblasic genes such as osteonectin (ONN), RUNX2 and Osterix, assessed via quantitative real-time PCR; the increase of osteocalcin (OCN) and osteopontin (OPN) at the protein level and the deposition of calcium phosphate determined by histological staining.
Intriguingly, we have observed a relationship between nanotopography and piezo-stimulated mechanotransduction and possibly see evidence of two differing osteogenic mechanisms at work. These data provide confidence in nanomechanotransduction for stem cell differentiation without dependence on soluble factors and complex chemistries.
In the future it is envisaged that this technology may have beneficial therapeutic applications in the healthcare industry, for conditions whose overall phenotype maybe characterized by weak or damaged bones (e.g., osteoporosis and bone fractures), and which can benefit from having an increased number of osteoblastic cells in vivo.
间充质干细胞(MSCs)具有很大的再生潜力,可以替代中胚层谱系中几种组织的受损细胞。这些细胞的潜力有望改变目前我们老龄化人口中许多退行性疾病的长期预后。我们努力证明我们能够使用高频(1000-5000 Hz)压电驱动纳米位移(16-30nm 位移)在垂直方向上诱导 MSC 成骨细胞分化。
通过定量实时 PCR 检测骨桥蛋白(ONN)、RUNX2 和 Osterix 等成骨基因的上调来确定成骨细胞分化;通过蛋白质水平测定骨钙素(OCN)和骨桥蛋白(OPN)的增加和组织化学染色确定磷酸钙的沉积。
有趣的是,我们观察到纳米形貌与压电刺激的机械转导之间存在关系,并且可能看到两种不同的成骨机制在起作用的证据。这些数据为基于纳米力学的干细胞分化提供了信心,而无需依赖可溶性因子和复杂的化学物质。
未来,预计这项技术可能在医疗保健行业中具有有益的治疗应用,适用于整体表型可能表现为骨骼脆弱或受损的疾病(例如骨质疏松症和骨折),并且可以受益于体内增加成骨细胞数量的疾病。