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

Somaa, F, Wang, T, Niclis, J, Bruggeman, K, Kauhausen, J, Guo, H, McDougall, S, Williams, R, Nisbet, D, Thompson, L and Parish, C 2017, 'Peptide-based scaffolds support human cortical progenitor graft integration to reduce atrophy and promote functional repair in a model of stroke', Cell Reports, vol. 20, no. 8, pp. 1964-1977.


Document type: Journal Article
Collection: Journal Articles

Title Peptide-based scaffolds support human cortical progenitor graft integration to reduce atrophy and promote functional repair in a model of stroke
Author(s) Somaa, F
Wang, T
Niclis, J
Bruggeman, K
Kauhausen, J
Guo, H
McDougall, S
Williams, R
Nisbet, D
Thompson, L
Parish, C
Year 2017
Journal name Cell Reports
Volume number 20
Issue number 8
Start page 1964
End page 1977
Total pages 14
Publisher Elsevier
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.
Subject Biomaterials
Keyword(s) cortex
human embryonic stem cells
hydrogel
integration
neural transplantation
self-assembling peptides
stroke
DOI - identifier 10.1016/j.celrep.2017.07.069
Copyright notice © 2017 The Authors. Creative Commons License.
ISSN 2211-1247
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