Promoting engraftment of transplanted neural stem cells/progenitors using biofunctionalised electrospun scaffolds

• Published in: Biomaterials Vol. 33; no. 36; pp. 9188 - 9197
• Main Authors: Wang, Ting-Yi, Forsythe, John S, Nisbet, David R, Parish, Clare L
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-12-2012
• Subjects: Advanced Basic Science; Animals; Cell Differentiation - physiology; Cell Proliferation; Cells, Cultured; Dentistry; Enzyme-Linked Immunosorbent Assay; Female; GDNF; Glial Cell Line-Derived Neurotrophic Factor - chemistry; Immunohistochemistry; Male; Mice; Microscopy, Electron, Scanning; Neural stem cell; Neural Stem Cells - cytology; Plasticity; Polycaprolactone; Polyesters - chemistry; Pregnancy; Rats; Scaffold; Tissue Scaffolds - chemistry; Transplantation; cell replacement therapy; CRT; E; soluble glial derived neurotrophic factor; CNS; Transplantation; Scaffold; GFP; iGDNF; Plasticity; embryonic day; ethylene diamine; poly ϵ-caprolactone; Polycaprolactone; ED; NSC; glial-cell derived neurotrophic factor; Neural stem cell; green fluorescent protein; central nervous system; GDNF; enzyme-linked immunosorbent assay; PCL; immobilised glial derived neurotrophic factor; sGDNF; ELISA
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2012.09.013

Abstract With the brain's limited capacity for repair, new and innovative approaches are required to promote regeneration. While neural transplantation for a number of neural disease/injuries have been demonstrated, major limitations in the field include poor cell survival and integration. This, in part, is due to the non-conducive environment of the adult brain, failing to provide adequate chemical and physical support for new neurons. Here we examine the capacity of fibrous poly ϵ-caprolactone (PCL) scaffolds, biofunctionalised with immobilised glial cell-derived neurotrophic factor (GDNF), to influence primary cortical neural stem cells/progenitors in vitro and enhance integration of these cells following transplantation into the brain parenchyma. Immobilisation of GDNF was confirmed prior to in vitro culturing and at 28 days after implantation into the brain, demonstrating long-term delivery of the protein. In vitro , we demonstrate that PCL with immobilised GDNF (iGDNF) significantly enhances cell viability and neural stem cell/progenitor proliferation compared to conventional 2-dimensional cultureware. Upon implantation, PCL scaffolds including iGDNF enhanced the survival, proliferation, migration, and neurite growth of transplanted cortical cells, whilst suppressing inflammatory reactive astroglia.