Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles

Biomaterials. 2012 Oct;33(30):7435-46. doi: 10.1016/j.biomaterials.2012.06.085. Epub 2012 Jul 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain / blood supply
  • Brain / pathology
  • Brain / physiopathology
  • Cell Differentiation
  • Cell Lineage
  • Humans
  • Inflammation / pathology
  • Lactic Acid / chemistry*
  • Microspheres*
  • Neovascularization, Physiologic*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / transplantation*
  • Phenotype
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Stem Cell Transplantation*
  • Stroke / pathology
  • Stroke / physiopathology*
  • Stroke / therapy
  • Vascular Endothelial Growth Factor A / metabolism*


  • Vascular Endothelial Growth Factor A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid