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In vivo migration of endogenous brain progenitor cells guided by an injectable peptide amphiphile biomaterial

Artikel i vetenskaplig tidskrift
Författare Reza Motalleb
E. J. Berns
Piyush Patel
J. Gold
S. I. Stupp
Hans-Georg Kuhn
Publicerad i Journal of Tissue Engineering and Regenerative Medicine
Volym 12
Nummer/häfte 4
Sidor E2123-E2133
ISSN 1932-6254
Publiceringsår 2018
Publicerad vid Institutionen för neurovetenskap och fysiologi
Sidor E2123-E2133
Språk en
Länkar doi.org/10.1002/term.2644
Ämnesord cell migration, doublecortin, nanofiber hydrogel, peptide amphiphile, rostral migratory stream, Tenascin-C, alternatively spliced region, promotes neurite outgrowth, adult, subventricular zone, human tenascin-c, monodomain gels, blood-vessels, growth-factor, rat-brain, stroke, injury, Cell Biology, Biotechnology & Applied Microbiology, Engineering, kseang j, 1995, brain research, v689, p207
Ämneskategorier Cell- och molekylärbiologi

Sammanfattning

Biomaterials hold great promise in helping the adult brain regenerate and rebuild after trauma. Peptide amphiphiles (PAs) are highly versatile biomaterials, gelling and forming macromolecular structures when exposed to physiological levels of electrolytes. We are here reporting on the first ever in vivo use of self-assembling PA carrying a Tenascin-C signal (E(2)Ten-C PA) for the redirection of endogenous neuroblasts in the rodent brain. The PA forms highly aligned nanofibers, displaying the migratory sequence of Tenascin-C glycoprotein as epitope. In this in vivo work, we have formed in situ a gel of aligned PA nanofibers presenting a migratory Tenascin-C signal sequence in the ventral horn of the rostral migratory stream, creating a track reaching the neocortex. Seven days posttransplant, doublecortin positive cells were observed migrating inside and alongside the injected biomaterial, reaching the cortex. We observed a 24-fold increase in number of redirected neuroblasts for the E(2)Ten-C PA-injected animals compared to control. We also found injecting the E(2)Ten-C PA to cause minimal neuroinflammatory response. Analysing GFAP(+) astrocytes and Iba1(+) microglia activation, the PA does not elicit a stronger neuroinflammatory response than would be expected from a small needle stab wound. Redirecting endogenous neuroblasts and increasing the number of cells reaching a site of injury using PAs may open up new avenues for utilizing the pool of neuroblasts and neural stem cells within the adult brain for regenerating damaged brain tissue and replacing neurons lost to injury.

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