Brain and spinal cord injury repair by implantation of human neural progenitor cells seeded onto polymer scaffolds.
Jeong Eun ShinKwangsoo JungMiri KimKyujin HwangHaejin LeeIl-Sun KimBae Hwan LeeIl-Shin LeeKook In ParkPublished in: Experimental & molecular medicine (2018)
Hypoxic-ischemic (HI) brain injury and spinal cord injury (SCI) lead to extensive tissue loss and axonal degeneration. The combined application of the polymer scaffold and neural progenitor cells (NPCs) has been reported to enhance neural repair, protection and regeneration through multiple modes of action following neural injury. This study investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived NPCs seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal HI brain injury or the hemisection cavity in an adult SCI. Implantation of human NPC (hNPC)-scaffold complex reduced the lesion volume, induced survival, engraftment, and differentiation of grafted cells, increased neovascularization, inhibited glial scar formation, altered the microglial/macrophage response, promoted neurite outgrowth and axonal extension within the lesion site, and facilitated the connection of damaged neural circuits. Tract tracing demonstrated that hNPC-scaffold grafts appear to reform the connections between neurons and their targets in both cerebral hemispheres in HI brain injury and protect some injured corticospinal fibers in SCI. Finally, the hNPC-scaffold complex grafts significantly improved motosensory function and attenuated neuropathic pain over that of the controls. These findings suggest that, with further investigation, this optimized multidisciplinary approach of combining hNPCs with biomaterial scaffolds provides a more versatile treatment for brain injury and SCI.
Keyphrases
- brain injury
- spinal cord injury
- neuropathic pain
- subarachnoid hemorrhage
- tissue engineering
- cerebral ischemia
- spinal cord
- endothelial cells
- pluripotent stem cells
- induced apoptosis
- high glucose
- healthcare
- adipose tissue
- multiple sclerosis
- transcranial magnetic stimulation
- atomic force microscopy
- vascular endothelial growth factor
- lipopolysaccharide induced
- combination therapy
- inflammatory response
- wound healing
- signaling pathway