Marycz Krzysztof, Lewandowski Daniel, Tomaszewski Krzysztof A, Henry Brandon M, Golec Edward B, Marędziak Monika
Faculty of Biology, University of Environmental and Life Sciences, Wroclaw, Poland; Wroclaw Research Centre EIT +, Wroclaw, Poland.
Department of Mechanics, Materials Science and Engineering, Wrocław University of Technology , Wrocław , Poland.
PeerJ. 2016 Feb 25;4:e1637. doi: 10.7717/peerj.1637. eCollection 2016.
The aim of this study was to evaluate if low-frequency, low-magnitude vibrations (LFLM) could enhance chondrogenic differentiation potential of human adipose derived mesenchymal stem cells (hASCs) with simultaneous inhibition of their adipogenic properties for biomedical purposes. We developed a prototype device that induces low-magnitude (0.3 g) low-frequency vibrations with the following frequencies: 25, 35 and 45 Hz. Afterwards, we used human adipose derived mesenchymal stem cell (hASCS), to investigate their cellular response to the mechanical signals. We have also evaluated hASCs morphological and proliferative activity changes in response to each frequency. Induction of chondrogenesis in hASCs, under the influence of a 35 Hz signal leads to most effective and stable cartilaginous tissue formation through highest secretion of Bone Morphogenetic Protein 2 (BMP-2), and Collagen type II, with low concentration of Collagen type I. These results correlated well with appropriate gene expression level. Simultaneously, we observed significant up-regulation of α3, α4, β1 and β3 integrins in chondroblast progenitor cells treated with 35 Hz vibrations, as well as Sox-9. Interestingly, we noticed that application of 35 Hz frequencies significantly inhibited adipogenesis of hASCs. The obtained results suggest that application of LFLM vibrations together with stem cell therapy might be a promising tool in cartilage regeneration.
本研究的目的是评估低频低强度振动(LFLM)是否能够增强人脂肪来源间充质干细胞(hASCs)的软骨形成分化潜能,同时抑制其成脂特性,以用于生物医学目的。我们开发了一种原型设备,该设备可诱导强度为0.3g的低频振动,频率分别为25Hz、35Hz和45Hz。之后,我们使用人脂肪来源间充质干细胞(hASCs)来研究它们对机械信号的细胞反应。我们还评估了hASCs在对每个频率反应时的形态和增殖活性变化。在35Hz信号的影响下,hASCs中软骨形成的诱导通过最高水平分泌骨形态发生蛋白2(BMP-2)和II型胶原蛋白,同时低水平分泌I型胶原蛋白,从而导致最有效和稳定的软骨组织形成。这些结果与适当的基因表达水平密切相关。同时,我们观察到在接受35Hz振动处理的成软骨细胞祖细胞中,α3、α4、β1和β3整合素以及Sox-9显著上调。有趣的是,我们注意到应用35Hz频率可显著抑制hASCs的成脂作用。所得结果表明,LFLM振动与干细胞疗法联合应用可能是软骨再生的一种有前景的工具。