Our goal is to develop an advanced in vitro system for nano-neurotoxicology that employs neural progenitor cells and tissue-engineering hydrogels. This work will enable rapid screening of engineered nanoparticles for neurotoxic hazards.
Engineered nanoparticles (NPs) have been shown to rapidly translocate along sensory nerves to the central nervous system (in animal models), cross the placental barrier (in humans), and are expected to cross the blood-brain barrier. In vivo studies are not practical for neurotoxic hazard assessment, however in vitro studies have well-known limitations including monocultures that limit cell-cell interactions and a stiff plastic environment that alters cell behavior.
Nanotoxicology studies have been criticized for employing doses that exceed what could be realistically encountered. High doses may drive an acute cellular response whereas lower, more realistic doses are likely to have subtle effects requiring functional endpoints. There remains an immediate need for improved in vitro methods for assessing neurotoxic hazards.
Additional Technical Details:
Neurite Outgrowth in Progenitor Cell Cultures. Neural progenitor cells differentiate into neurons and glial cells (astrocytes and oligodendrocytes). We recently demonstrated that lithium chloride, a known neurotoxin, inhibits neurite outgrowth in differentiating progenitor cell cultures and can serve as a control for nanoparticle studies.
From K.M. Jeerage, T.L. Oreskovic, Submitted to Neurotoxicology (2011)
Nanoparticle Uptake by Neural Cells. Bioavailability is expected to impact the ability of nanoparticles to interfere with cellular processes. Quantitative fluorescence measurements show that neural progenitor cells have significantly different uptake of carboxyl-terminated quantum dots than model neural cells.
From K.M. Jeerage, T.L. Oreskovic, E. Mansfield, MRS Workshop on Functionalized Nanobiomaterials (2010)
Start Date:April 24, 2008
Lead Organizational Unit:mml
Project Summary (PDF)
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