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

Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): 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
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.

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Teaser

Somaa et al. examine the capacity of peptide-based scaffolds to structurally and functionally support human pluripotent stem cell-derived neural transplants in the stroke-injured brain. Scaffolds promoted graft maturation and integration and reduced host tissue atrophy, resulting in improved motor function over a period of 9 months.


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