This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Systemic injection of adult neural stem cells (aNSCs) into mice with experimental autoimmune encephalomyelitis (EAE) can provide a source of new oligodendrocytes that can remyelinate demyelinated or dysmyelinated axons. However, systemically-injected aNSCs often fail to differentiate and remain undifferentiated in peri-vascular domains of demyelinated lesions where they promote apoptosis of blood-born CNS-infiltrating encephalitogenic T cells. We discovered that a high molecular weight form of hyaluronan (HA), accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor cell maturation. The major receptor for HA is the CD44 transmembrane glycoprotein. Our preliminary data suggest that HA and CD44 regulate functions relevant to how aNSCs behave in demyelinated lesions, including NSC differentiation and production of pro-inflammatory cytokines. We propose that CD44 and HA are critical mediators of aNSC recruitment to demyelinated lesions and that HA, at least, can regulate whether NSCs differentiate into myelinating cells or fail to differentiate and promote T cell apoptosis at perivascular domains where HA accumulates. In this study, we aim to test the hypotheses: (1) That high molecular weight HA inhibits aNSC differentiation;(2) That NSC homing to EAE lesions depends on interactions between CD44 and HA;and (3) That HA regulates the immunomodulatory activities of NSC.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-52
Application #
8357755
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
52
Fiscal Year
2011
Total Cost
$36,286
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C et al. (2016) Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Nat Commun 7:11138
Sylwester, Andrew; Nambiar, Kate Z; Caserta, Stefano et al. (2016) A new perspective of the structural complexity of HCMV-specific T-cell responses. Mech Ageing Dev 158:14-22
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