Department of Biomedical Engineering, Carnegie Mellon University, Pittsburg, PA 15213, United States.
J Biomech. 2012 Apr 30;45(7):1280-7. doi: 10.1016/j.jbiomech.2012.01.032. Epub 2012 Feb 18.
Therapies using adult stem cells often require mechanical manipulation such as injection or incorporation into scaffolds. However, force-induced rupture and mechanosensitivity of cells during manipulation is largely ignored. Here, we image cell mechanical structures and perform a biophysical characterization of three different types of human adult stem cells: bone marrow CD34+ hematopoietic, bone marrow mesenchymal and perivascular mesenchymal stem cells. We use micropipette aspiration to characterize cell mechanics and quantify deformation of subcellular structures under force and its contribution to global cell deformation. Our results suggest that CD34+ cells are mechanically suitable for injection systems since cells transition from solid- to fluid-like at constant aspiration pressure, probably due to a poorly developed actin cytoskeleton. Conversely, mesenchymal stem cells from the bone marrow and perivascular niches are more suitable for seeding into biomaterial scaffolds since they are mechanically robust and have developed cytoskeletal structures that may allow cellular stable attachment and motility through solid porous environments. Among these, perivascular stem cells cultured in 6% oxygen show a developed cytoskeleton but a more compliant nucleus, which can facilitate the penetration into pores of tissues or scaffolds. We confirm the relevance of our measurements using cell motility and migration assays and measure survival of injected cells. Since different types of adult stem cells can be used for similar applications, we suggest considering mechanical properties of stem cells to match optimal mechanical characteristics of therapies.
利用成体干细胞的疗法通常需要机械操作,如注射或纳入支架。然而,在操作过程中,细胞的力诱导破裂和机械敏感性在很大程度上被忽视了。在这里,我们对三种不同类型的人成体干细胞:骨髓 CD34+造血细胞、骨髓间充质干细胞和血管周间充质干细胞进行了细胞力学结构成像和生物物理特性分析。我们使用微吸管抽吸来描述细胞力学特性,并在力作用下量化亚细胞结构的变形及其对整体细胞变形的贡献。我们的结果表明,CD34+细胞适合于注射系统,因为细胞在恒定的抽吸压力下从固体样态转变为流体样态,这可能是由于肌动蛋白细胞骨架发育不良。相反,骨髓和血管周龛中的间充质干细胞更适合种植到生物材料支架中,因为它们具有机械坚固性和发育良好的细胞骨架结构,这可能允许细胞通过固体多孔环境进行稳定附着和迁移。在这些细胞中,在 6%氧气中培养的血管周干细胞表现出发达的细胞骨架,但核更具弹性,这可以促进其穿透组织或支架的孔隙。我们通过细胞迁移和迁移测定证实了我们测量的相关性,并测量了注射细胞的存活率。由于不同类型的成体干细胞可用于类似的应用,因此我们建议考虑干细胞的机械特性,以匹配治疗的最佳机械特性。