1 Department of Tissue Culture and Stem Cells, Institute of Experimental Medicine, CAS, Prague, Czech Republic.
2 Department of Polymer Networks and Gels, Institute of Macromolecular Chemistry, CAS, Prague, Czech Republic.
Cell Transplant. 2019 Apr;28(4):400-412. doi: 10.1177/0963689718823705. Epub 2019 Jan 18.
Spinal cord injury (SCI), is a devastating condition leading to the loss of locomotor and sensory function below the injured segment. Despite some progress in acute SCI treatment using stem cells and biomaterials, chronic SCI remains to be addressed. We have assessed the use of laminin-coated hydrogel with dual porosity, seeded with induced pluripotent stem cell-derived neural progenitors (iPSC-NPs), in a rat model of chronic SCI. iPSC-NPs cultured for 3 weeks in hydrogel in vitro were positive for nestin, glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2). These cell-polymer constructs were implanted into a balloon compression lesion, 5 weeks after lesion induction. Animals were behaviorally tested, and spinal cord tissue was immunohistochemically analyzed 28 weeks after SCI. The implanted iPSC-NPs survived in the scaffold for the entire experimental period. Host axons, astrocytes and blood vessels grew into the implant and an increased sprouting of host TH fibers was observed in the lesion vicinity. The implantation of iPSC-NP-LHM cell-polymer construct into the chronic SCI led to the integration of material into the injured spinal cord, reduced cavitation and supported the iPSC-NPs survival, but did not result in a statistically significant improvement of locomotor recovery.
脊髓损伤(SCI)是一种破坏性疾病,会导致受伤节段以下的运动和感觉功能丧失。尽管使用干细胞和生物材料在急性 SCI 治疗方面取得了一些进展,但慢性 SCI 仍有待解决。我们评估了在慢性 SCI 大鼠模型中使用具有双重孔隙率的层粘连蛋白涂层水凝胶,种植诱导多能干细胞衍生的神经祖细胞(iPSC-NP)。在体外水凝胶中培养 3 周的 iPSC-NP 对巢蛋白、胶质纤维酸性蛋白(GFAP)和微管相关蛋白 2(MAP2)呈阳性。在损伤诱导后 5 周,将这些细胞-聚合物构建体植入气囊压迫性损伤部位。在 SCI 后 28 周,对动物进行行为测试,并对脊髓组织进行免疫组织化学分析。植入的 iPSC-NP 在整个实验期间都在支架中存活。宿主轴突、星形胶质细胞和血管长入植入物,在损伤部位附近观察到宿主 TH 纤维的大量发芽。将 iPSC-NP-LHM 细胞-聚合物构建体植入慢性 SCI 会导致材料整合到受伤的脊髓中,减少空洞化并支持 iPSC-NP 的存活,但并没有导致运动功能恢复的统计学显著改善。