School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK.
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Med Eng Phys. 2019 Nov;73:18-29. doi: 10.1016/j.medengphy.2019.07.013. Epub 2019 Aug 9.
Improving stem cell (SC) deformability using pre-treatment strategies, or isolating more deformable sub-populations, may prevent non-specific entrapment of injected cells, maintain circulating numbers and thus increase the likelihood of capture by microvessels in injured organs. However, nothing is currently known about the basic mechanical properties of SCs, particularly with regards their elastic characteristics. This study therefore aimed to determine the mechanical characteristics of haematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) with comparisons made to neutrophils.
Micromanipulation and atomic force microscopy (AFM) were used to quantitate mechanical properties following large and small deformations respectively of neutrophils, MSCs and naïve and stromal cell-derived factor-1α (SDF-1ɑ) or hydrogen peroxide (HO) pre-treated HSCs.
Neutrophils and HSCs underwent rupture at ∼80% deformation. Nominal rupture stress (σ), nominal rupture tension (T) and the Young's/elastic modulus at large deformations was significantly higher for neutrophils indicating they were stiffer and less deformable than HSCs. Surprisingly, MSCs did not rupture and were as deformable as HSCs despite their large size. Pre-treatment increased HSC deformability as indicated by lower rupture force, σ T and Young's modulus at large deformations. AFM demonstrated that pre-treatment increased the Young's modulus at smaller deformations indicating the HSC surface stiffened. This was accompanied by increased F-actin accumulation and its localisation in the cell cortex.
This is the first study to precisely demonstrate that mechanical distinctions exist amongst different therapeutic SCs with regards their deformability and rupture response to applied stress. This can potentially be utilized as label-free markers in microfluidic cell sorting systems to separate sub-populations of potentially more therapeutic SCs.
通过预处理策略提高干细胞（SC）的变形能力，或分离更具变形能力的亚群，可能防止注射细胞的非特异性捕获，保持循环数量，从而增加受损器官中微血管捕获的可能性。然而，目前对于 SC 的基本力学特性，特别是其弹性特性，还一无所知。因此，本研究旨在确定造血干细胞（HSCs）和间充质干细胞（MSCs）的力学特性，并与中性粒细胞进行比较。
微操作和原子力显微镜（AFM）分别用于定量中性粒细胞、MSCs 以及未经预处理和基质细胞衍生因子-1α（SDF-1ɑ）或过氧化氢（HO）预处理的 HSCs 在大变形和小变形下的力学特性。
中性粒细胞和 HSCs 在约 80%变形时发生破裂。名义破裂应力（σ）、名义破裂张力（T）和大变形时的杨氏/弹性模量均显著高于中性粒细胞，表明它们比 HSCs 更硬、更不易变形。令人惊讶的是，尽管 MSC 体积较大，但它们不会破裂且与 HSCs 一样具有变形能力。预处理可提高 HSC 的变形能力，表现为大变形时破裂力、σ、T 和杨氏模量降低。AFM 表明，预处理可提高小变形时的杨氏模量，表明 HSC 表面变硬。这伴随着 F-肌动蛋白的积累及其在细胞皮质中的局部化增加。
这是第一项精确表明不同治疗性 SC 在变形能力和对施加应力的破裂反应方面存在差异的研究。这可潜在地用作微流控细胞分选系统中的无标记标记物，以分离潜在更具治疗效果的 SC 亚群。
