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bioRxiv · 10.1101/2020.07.28.224899

Guiding oligodendrocyte precursor cell maturation with urokinase plasminogen activator-degradable elastin-like protein hydrogels

Meco, E.·Zheng, W. S.·Sharma, A. H.·Lampe, K. J.
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Abstract

Demyelinating injuries and diseases, like multiple sclerosis, affect millions of people worldwide. Oligodendrocyte precursor cells (OPCs) have the potential to repair demyelinated tissue because they can both self-renew and differentiate into oligodendrocytes (OLs), the myelin producing cells of the central nervous system (CNS). Cell-matrix interactions impact OPC differentiation into OLs, but the process is not fully understood. Biomaterial hydrogel systems help to elucidate cell-matrix interactions because they can mimic specific properties of native CNS tissue in an in vitro setting. We investigated whether OPC maturation into OLs is influenced by interacting with a urokinase plasminogen activator (uPA) degradable extracellular matrix (ECM). uPA is a proteolytic enzyme that is transiently upregulated in the developing rat brain, with peak uPA expression correlating with an increase in myelin production in vivo. OPC-like cells isolated through the Mosaic Analysis with Double Marker technique (MADM OPCs) produced low molecular weight uPA in culture. MADM OPCs were encapsulated into two otherwise similar elastin-like protein (ELP) hydrogel systems: one that was uPA degradable and one that was non-degradable. Encapsulated MADM OPCs had similar viability, proliferation, and metabolic activity in uPA degradable and non-degradable ELP hydrogels. Expression of OPC maturation-associated genes, however, indicated that uPA degradable ELP hydrogels promoted MADM OPC maturation although not sufficiently for these cells to differentiate into OLs. Graphical Abstract - For table of contents only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/224899v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@4f3356org.highwire.dtl.DTLVardef@1b369d4org.highwire.dtl.DTLVardef@1e8df31org.highwire.dtl.DTLVardef@1954777_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Meco, E., Zheng, W. S., Sharma, A. H., Lampe, K. J.. 2020-07-29. Guiding oligodendrocyte precursor cell maturation with urokinase plasminogen activator-degradable elastin-like protein hydrogels. https://doi.org/10.1101/2020.07.28.224899

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