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

• 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.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

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

peptide amphiphile

Publication and Content Type

ref (subject category)

art (subject category)