Peptide-Based Scaffolds Support Human Cortical Progenitor Graft Integration to Reduce Atrophy and Promote Functional Repair in a Model of Stroke

Fahad A. Somaa, Ting Yi Wang, Jonathan C. Niclis, Kiara F. Bruggeman, Jessica A. Kauhausen, Haoyao Guo, Stuart McDougall, Richard J. Williams, David R. Nisbet, Lachlan H. Thompson, Clare L. Parish

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

Abstract

Stem cell transplants offer significant hope for brain repair following ischemic damage. Pre-clinical work suggests that therapeutic mechanisms may be multi-faceted, incorporating bone-fide circuit reconstruction by transplanted neurons, but also protection/regeneration of host circuitry. Here, we engineered hydrogel scaffolds to form “bio-bridges” within the necrotic lesion cavity, providing physical and trophic support to transplanted human embryonic stem cell-derived cortical progenitors, as well as residual host neurons. Scaffolds were fabricated by the self-assembly of peptides for a laminin-derived epitope (IKVAV), thereby mimicking the brain's major extracellular protein. Following focal ischemia in rats, scaffold-supported cell transplants induced progressive motor improvements over 9 months, compared to cell- or scaffold-only implants. These grafts were larger, exhibited greater neuronal differentiation, and showed enhanced electrophysiological properties reflective of mature, integrated neurons. Varying graft timing post-injury enabled us to attribute repair to both neuroprotection and circuit replacement. These findings highlight strategies to improve the efficiency of stem cell grafts for brain repair.

Original languageEnglish
Pages (from-to)1964-1977
Number of pages14
JournalCell Reports
Volume20
Issue number8
DOIs
Publication statusPublished - 22 Aug 2017
Externally publishedYes

Keywords

  • cortex
  • human embryonic stem cells
  • hydrogel
  • integration
  • neural transplantation
  • self-assembling peptides
  • stroke

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