Departments of Radiology, University of Pittsburgh, Pittsburgh, USA.
Departments of Bioengineering, University of Pittsburgh, Pittsburgh, USA.
Sci Rep. 2018 Jun 15;8(1):9194. doi: 10.1038/s41598-018-27568-x.
Intracerebral implantation of cell suspensions is finding its clinical translation with encouraging results in patients with stroke. However, the survival of cells in the brain remains poor. Although the biological potential of neural stem cells (NSCs) is widely documented, the biomechanical effects of delivering cells through a syringe-needle remain poorly understood. We here detailed the biomechanical forces (pressure, shear stress) that cells are exposed to during ejection through different sized needles (20G, 26G, 32G) and syringes (10, 50, 250 µL) at relevant flow rates (1, 5, 10 µL/min). A comparison of 3 vehicles, Phosphate Buffered Saline (PBS), Hypothermosol (HTS), and Pluronic, indicated that less viscous vehicles are favorable for suspension with a high cell volume fraction to minimize sedimentation. Higher suspension viscosity was associated with greater shear stress. Higher flow rates with viscous vehicle, such as HTS reduced viability by ~10% and also produced more apoptotic cells (28%). At 5 µL/min ejection using a 26G needle increased neuronal differentiation for PBS and HTS suspensions. These results reveal the biological impact of biomechanical forces in the cell delivery process. Appropriate engineering strategies can be considered to mitigate these effects to ensure the efficacious translation of this promising therapy.
脑内细胞悬液移植在脑卒中患者中取得了令人鼓舞的临床转化效果。然而，细胞在大脑中的存活率仍然很低。尽管神经干细胞（NSC）的生物学潜力已被广泛证实，但通过注射器-针头输送细胞的生物力学效应仍知之甚少。我们在这里详细描述了细胞在通过不同大小的针头（20G、26G、32G）和注射器（10、50、250μL）以相关流速（1、5、10μL/min）射出时所承受的生物力学力（压力、剪切应力）。将 3 种载体（磷酸盐缓冲盐水（PBS）、Hypothermosol（HTS）和 Pluronic）进行比较，结果表明，粘性较低的载体有利于高细胞体积分数的悬浮，以最大程度地减少沉淀。较高的悬浮粘度与较大的剪切应力相关。高粘度的载体（如 HTS）在较高流速下会降低约 10%的细胞活力，并产生更多的凋亡细胞（28%）。使用 26G 针头以 5μL/min 的速度射出时，PBS 和 HTS 悬浮液可增加神经元分化。这些结果揭示了细胞输送过程中生物力学力的生物学影响。可以考虑采用适当的工程策略来减轻这些影响，以确保这种有前途的治疗方法能够有效地转化。
