title: Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles.
abstract: Replacing the tissue lost after a stroke potentially provides a new neural substrate to promote recovery. However, significant neurobiological and biotechnological challenges need to be overcome to make this possibility into a reality. Human neural stem cells (hNSCs) can differentiate into mature brain cells, but require a structural support that retains them within the cavity and affords the formation of a de novo tissue. Nevertheless, in our previous work, even after a week, this primitive tissue is void of a vasculature that could sustain its long-term viability. Therefore, tissue engineering strategies are required to develop a vasculature. Vascular endothelial growth factor (VEGF) is known to promote the proliferation and migration of endothelial cells during angio- and arteriogenesis. VEGF by itself here did not affect viability or differentiation of hNSCs, whereas growing cells on poly(D,L-lactic acid-co-glycolic acid) (PLGA) microparticles, with or without VEGF, doubled astrocytic and neuronal differentiation. Secretion of a burst and a sustained delivery of VEGF from the microparticles in vivo attracted endothelial cells from the host into this primitive tissue and in parts established a neovasculature, whereas in other parts endothelial cells were merely interspersed with hNSCs. There was also evidence of a hypervascularization indicating that further work will be required to establish an adequate level of vascularization. It is therefore possible to develop a putative neovasculature within de novo tissue that is forming inside a tissue cavity caused by a stroke.
authors: Kings College London, Institute of Psychiatry, Department of Neuroscience, London, UK.
authors: Ellen
authors: E
authors: Bible
authors: Omar
authors: O
authors: Qutachi
authors: David Y S
authors: DY
authors: Chau
authors: Morgan R
authors: MR
authors: Alexander
authors: Kevin M
authors: KM
authors: Shakesheff
authors: Michel
authors: M
authors: Modo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation; D019070:Cell Lineage; D006801:Humans; D007249:Inflammation / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D018919:Neovascularization, Physiologic; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D010641:Phenotype; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D033581:Stem Cell Transplantation; D020521:Stroke / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid