George Paul M, Bliss Tonya M, Hua Thuy, Lee Alex, Oh Byeongtaek, Levinson Alexa, Mehta Swapnil, Sun Guohua, Steinberg Gary K
Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA; Stanford Stroke Center and Stanford University School of Medicine, Stanford, CA, USA.
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA; Stanford Stroke Center and Stanford University School of Medicine, Stanford, CA, USA.
Biomaterials. 2017 Oct;142:31-40. doi: 10.1016/j.biomaterials.2017.07.020. Epub 2017 Jul 12.
Exogenous human neural progenitor cells (hNPCs) are promising stroke therapeutics, but optimal delivery conditions and exact recovery mechanisms remain elusive. To further elucidate repair processes and improve stroke outcomes, we developed an electrically conductive, polymer scaffold for hNPC delivery. Electrical stimulation of hNPCs alters their transcriptome including changes to the VEGF-A pathway and genes involved in cell survival, inflammatory response, and synaptic remodeling. In our experiments, exogenous hNPCs were electrically stimulated (electrically preconditioned) via the scaffold 1 day prior to implantation. After in vitro stimulation, hNPCs on the scaffold are transplanted intracranially in a distal middle cerebral artery occlusion rat model. Electrically preconditioned hNPCs improved functional outcomes compared to unstimulated hNPCs or hNPCs where VEGF-A was blocked during in vitro electrical preconditioning. The ability to manipulate hNPCs via a conductive scaffold creates a new approach to optimize stem cell-based therapy and determine which factors (such as VEGF-A) are essential for stroke recovery.
外源性人类神经祖细胞(hNPCs)是很有前景的中风治疗手段,但最佳递送条件和确切的恢复机制仍不清楚。为了进一步阐明修复过程并改善中风预后,我们开发了一种用于hNPC递送的导电聚合物支架。对hNPCs进行电刺激会改变其转录组,包括VEGF-A通路以及参与细胞存活、炎症反应和突触重塑的基因的变化。在我们的实验中,外源性hNPCs在植入前1天通过该支架进行电刺激(电预处理)。体外刺激后,将支架上的hNPCs移植到大脑中动脉远端闭塞大鼠模型的颅内。与未刺激的hNPCs或在体外电预处理期间VEGF-A被阻断的hNPCs相比,电预处理的hNPCs改善了功能结局。通过导电支架操纵hNPCs的能力为优化基于干细胞的治疗以及确定哪些因素(如VEGF-A)对中风恢复至关重要创造了一种新方法。