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Peptide-based scaffolds support human cortical progenitor graft integration to reduce atrophy and promote functional repair in a model of stroke

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journal contribution
posted on 22.08.2017, 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 Parish
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.

History

Journal

Cell reports

Volume

20

Issue

8

Pagination

1964 - 1977

Publisher

Elsevier

Location

Amsterdam, The Netherlands

ISSN

2211-1247

eISSN

2211-1247

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2017, The Authors