Tianjin Key Laboratory of Neurotrauma Repair, Pingjin Hospital Brain Center, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China; School of Precision Instrument & Optoelectronics Engineering of Tianjin University, Tianjin 300072, China.
Tianjin Key Laboratory of Neurotrauma Repair, Pingjin Hospital Brain Center, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
Neuroscience. 2018 May 1;377:1-11. doi: 10.1016/j.neuroscience.2018.02.013. Epub 2018 Feb 23.
Both chemical and physical microenvironments appear to be important for lineage specification of umbilical cord mesenchymal stem cells (UCMSCs). However, physical factors such as the elastic modulus in traumatic brain injury (TBI) are seldom studied. Intracranial hypertension and cerebral edema after TBI may change the brain's physical microenvironment, which inhibits neural lineage specification of transplanted UCMSCs. The purpose of this study is to investigate the potential regulatory effect of mild hypothermia on the elastic modulus of the injured brain. First, we found that more UCMSCs grown on gels mimicking the elastic modulus of the brain (0.5 kPa) differentiated into neural cells, which were verified with the formation of branched cells and the expression of neural markers. Then, UCMSCs were transplanted into TBI rats, and we observed that mild hypothermia resulted in the differentiation of more neurons and astrocytes from transplanted UCMSCs. To demonstrate that more neural specification of UCMSCs was due to the regulation of the elastic modulus, we monitored intracranial pressure and cerebral edema. The results showed that mild hypothermia significantly reduced intracranial pressure and brain water content, indicating modulation of the elastic modulus by mild hypothermia. An examination with atomic force microscopy (AFM) in a cell injury model in vitro further verified hypothermia-regulated elastic modulus. In this study, we found a novel role of mild hypothermia in modulating the elastic modulus of the injured brain, resulting in the promotion of neural lineage specification of UCMSCs, which suggested that the combination of mild hypothermia had more advantages in cell-based therapy after TBI.
化学和物理微环境似乎对脐带间充质干细胞（UCMSCs）的谱系特化都很重要。然而，创伤性脑损伤（TBI）中的物理因素，如弹性模量，很少被研究。TBI 后的颅内高压和脑水肿可能会改变大脑的物理微环境，从而抑制移植的 UCMSCs 的神经谱系特化。本研究旨在探讨轻度低温对损伤大脑弹性模量的潜在调节作用。首先，我们发现，在模拟大脑弹性模量（0.5kPa）的凝胶上生长的更多 UCMSCs 分化为神经细胞，这通过形成分支细胞和表达神经标记物得到了验证。然后，将 UCMSCs 移植到 TBI 大鼠中，我们观察到轻度低温导致更多来自移植的 UCMSCs 的神经元和星形胶质细胞分化。为了证明 UCMSCs 的更多神经特化是由于弹性模量的调节，我们监测了颅内压和脑水肿。结果表明，轻度低温显著降低了颅内压和脑水含量，表明轻度低温对弹性模量的调节作用。体外细胞损伤模型中的原子力显微镜（AFM）检查进一步验证了低温调节弹性模量。在这项研究中，我们发现轻度低温在调节损伤大脑的弹性模量方面具有新的作用，从而促进了 UCMSCs 的神经谱系特化，这表明在 TBI 后细胞治疗中，低温联合治疗具有更多优势。
