Department of Neurology and the Neurological Sciences, 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 Neurology and the Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Biomaterials. 2018 Sep;178:63-72. doi: 10.1016/j.biomaterials.2018.06.010. Epub 2018 Jun 14.
Currently, no medical therapies exist to augment stroke recovery. Stem cells are an intriguing treatment option being evaluated, but cell-based therapies have several challenges including developing a stable cell product with long term reproducibility. Since much of the improvement observed from cellular therapeutics is believed to result from trophic factors the stem cells release over time, biomaterials are well-positioned to deliver these important molecules in a similar fashion. Here we show that essential trophic factors secreted from stem cells can be effectively released from a multi-component hydrogel system into the post-stroke environment. Using our polymeric system to deliver VEGF-A and MMP-9, we improved recovery after stroke to an equivalent degree as observed with traditional stem cell treatment in a rodent model. While VEGF-A and MMP-9 have many unique mechanisms of action, connective tissue growth factor (CTGF) interacts with both VEGF-A and MMP-9. With our hydrogel system as well as with stem cell delivery, the CTGF pathway is shown to be downregulated with improved stroke recovery.
目前，尚无医学疗法可增强中风后的恢复。干细胞是一种备受关注的治疗选择，正在进行评估，但细胞疗法存在几个挑战，包括开发具有长期重现性的稳定细胞产品。由于细胞治疗观察到的大部分改善被认为是源自干细胞随时间释放的营养因子，因此生物材料非常适合以类似方式递送这些重要分子。在这里，我们表明干细胞分泌的必需营养因子可以从多组分水凝胶系统中有效地释放到中风后的环境中。使用我们的聚合物系统递送 VEGF-A 和 MMP-9，我们改善了中风后的恢复程度，与在啮齿动物模型中观察到的传统干细胞治疗效果相当。虽然 VEGF-A 和 MMP-9 具有许多独特的作用机制，但结缔组织生长因子 (CTGF) 与 VEGF-A 和 MMP-9 相互作用。通过我们的水凝胶系统以及干细胞递送，CTGF 途径的下调与中风恢复的改善有关。
