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Cell Rep. 2017 Aug 22;20(8):1964-1977. doi: 10.1016/j.celrep.2017.07.069.

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

Author information

1
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052, Australia.
2
Laboratory of Advanced Materials, Research School of Engineering, The Australian National University, Canberra, ACT 2601, Australia.
3
School of Engineering, RMIT University, Melbourne, VIC 3001, Australia.
4
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: clare.parish@florey.edu.au.

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.

KEYWORDS:

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

PMID:
28834757
DOI:
10.1016/j.celrep.2017.07.069
[Indexed for MEDLINE]
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