The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue

Nat Biotechnol. 2002 Nov;20(11):1111-7. doi: 10.1038/nbt751. Epub 2002 Oct 15.

Abstract

Hypoxic-ischemic injury is a prototype for insults characterized by extensive tissue loss. Seeding neural stem cells (NSCs) onto a polymer scaffold that was subsequently implanted into the infarction cavities of mouse brains injured by hypoxia-ischemia allowed us to observe the multiple reciprocal interactions that spontaneously ensue between NSCs and the extensively damaged brain: parenchymal loss was dramatically reduced, an intricate meshwork of many highly arborized neurites of both host- and donor-derived neurons emerged, and some anatomical connections appeared to be reconstituted. The NSC-scaffold complex altered the trajectory and complexity of host cortical neurites. Reciprocally, donor-derived neurons were seemingly capable of directed, target-appropriate neurite outgrowth (extending axons to the opposite hemisphere) without specific external instruction, induction, or genetic manipulation of host brain or donor cells. These "biobridges" appeared to unveil or augment a constitutive reparative response by facilitating a series of reciprocal interactions between NSC and host, including promoting neuronal differentiation, enhancing the elaboration of neural processes, fostering the re-formation of cortical tissue, and promoting connectivity. Inflammation and scarring were also reduced, facilitating reconstitution.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biocompatible Materials
  • Brain / pathology
  • Brain / surgery
  • Clone Cells
  • Hypoxia-Ischemia, Brain / complications
  • Hypoxia-Ischemia, Brain / pathology*
  • Hypoxia-Ischemia, Brain / therapy*
  • Mice
  • Nerve Degeneration / etiology
  • Nerve Degeneration / pathology
  • Nerve Degeneration / surgery
  • Nerve Regeneration*
  • Neural Pathways / pathology
  • Neurons / pathology*
  • Polyglycolic Acid
  • Prostheses and Implants
  • Stem Cell Transplantation*
  • Stem Cells / pathology*
  • Textiles

Substances

  • Biocompatible Materials
  • Polyglycolic Acid