DWI─Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, Aachen D-52074, Germany.
Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 1-2, Aachen D-52074, Germany.
ACS Appl Mater Interfaces. 2024 Jan 10;16(1):30-43. doi: 10.1021/acsami.3c11808. Epub 2023 Dec 27.
Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple lineages and can be harvested relatively easily from adults, making them a promising cell source for regenerative therapies. While it is well-known how to consistently differentiate MSCs into adipose, chondrogenic, and osteogenic lineages by treatment with biochemical factors, the number of studies exploring how to achieve this with mechanical signals is limited. A relatively unexplored area is the effect of cyclic forces on the MSC differentiation. Recently, our group developed a thermoresponsive -ethyl acrylamide/-isopropylacrylamide (NIPAM/NEAM) hydrogel supplemented with gold nanorods that are able to convert near-infrared light into heat. Using light pulses allows for local hydrogel collapse and swelling with physiologically relevant force and frequency. In this study, MSCs are cultured on this hydrogel system with a patterned surface and exposed to intermittent or continuous actuation of the hydrogel for 3 days to study the effect of actuation on MSC differentiation. First, cells are harvested from the bone marrow of three donors and tested for their MSC phenotype, meeting the following criteria: the harvested cells are adherent and demonstrate a fibroblast-like bipolar morphology. They lack the expression of CD34 and CD45 but do express CD73, CD90, and CD105. Additionally, their differentiation potential into adipogenic, chondrogenic, and osteogenic lineages is validated by the addition of standardized differentiation media. Next, MSCs are exposed to intermittent or continuous actuation, which leads to a significantly enhanced cell spreading compared to nonactuated cells. Moreover, actuation results in nuclear translocation of Runt-related transcription factor 2 and the Yes-associated protein. Together, these results indicate that cyclic mechanical stimulation on a soft, ridged substrate modulates the MSC fate commitment in the direction of osteogenesis.
间充质干细胞（MSCs）具有向多个谱系分化的潜力，并且可以从成年人中相对容易地收获，因此它们是再生治疗有前途的细胞来源。虽然通过用生化因子处理来一致地将 MSCs 分化为脂肪、软骨和成骨谱系已经众所周知，但探索如何通过机械信号实现这一点的研究数量有限。一个相对未知的领域是循环力对 MSC 分化的影响。最近，我们小组开发了一种热敏性 -乙基丙烯酰胺/-异丙基丙烯酰胺（NIPAM/NEAM）水凝胶，其中补充了能够将近红外光转化为热的金纳米棒。使用光脉冲允许局部水凝胶塌陷和肿胀，具有生理相关的力和频率。在这项研究中，将 MSCs 培养在具有图案化表面的这种水凝胶系统上，并间歇性或连续地对水凝胶进行激活 3 天，以研究激活对 MSC 分化的影响。首先，从三名供体的骨髓中收获细胞，并对其 MSC 表型进行测试，符合以下标准：收获的细胞是贴壁的，表现出类似成纤维细胞的双极形态。它们缺乏 CD34 和 CD45 的表达，但表达 CD73、CD90 和 CD105。此外，通过添加标准化分化培养基验证了它们向脂肪、软骨和成骨谱系分化的潜力。接下来，将 MSCs 暴露于间歇性或连续激活，与未激活的细胞相比，这导致细胞显著扩展。此外，激活导致 runt 相关转录因子 2 和 Yes 相关蛋白的核易位。总之，这些结果表明，在软、脊状基底上的周期性机械刺激调节 MSC 命运决定向成骨方向发展。
