williams-peptidebased-2017.pdf (6.48 MB)
Peptide-based scaffolds support human cortical progenitor graft integration to reduce atrophy and promote functional repair in a model of stroke
journal contribution
posted on 2017-08-22, 00:00 authored by Fahad A Somaa, Ting-Yi Wang, Jonathan C Niclis, Kiara F Bruggeman, Jessica A Kauhausen, Haoyao Guo, Stuart McDougall, Richard WilliamsRichard Williams, David R Nisbet, Lachlan H Thompson, Clare L ParishStem 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.
History
Journal
Cell reportsVolume
20Issue
8Pagination
1964 - 1977Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
Link to full text
ISSN
2211-1247eISSN
2211-1247Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2017, The AuthorsUsage metrics
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cortexhuman embryonic stem cellshydrogelintegrationneural transplantationself-assembling peptidesstrokeScience & TechnologyLife Sciences & BiomedicineCell BiologyPLURIPOTENT STEM-CELLSRAT PARKINSON-MODELINTRACEREBRAL TRANSPLANTATIONNANOFIBER SCAFFOLDCEREBRAL-ISCHEMIADOPAMINE NEURONSIMPROVE RECOVERYINJURED BRAININ-VIVOSURVIVAL
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