Studies performed using magnetically labeled lymph node derived cells in the marmoset EAE model have shown the ability to detect labeled cells in the brain and spinal cord on a clinical MRI scanner. These results will serve as the basis for moving forward to magnetically label cells harvested during apheresis and re-infuse autologous cells into patients with MS to monitor the migration of labeled stem cells or peripheral blood mononuclear cells into the central nervous system by MRI. In the marmoset EAE model immunohistochemical techniques were used to identify and describe cortical lesions in marmosets with experimental autoimmune encephalomyelitis (EAE). Using antibodies to proteolipid protein (PLP) cortical lesions in were identified in animals. These lesions were subdivided into leucocortical, intracortical and subpial lesions. The density of inflammatory cells within lesions using a double labeling protocol which employed anti-PLP in addition to antibodies against markers of B-lymphocytes (CD20), T-lymphocytes (CD3), macrophages (MAC387) and MHC-II expressing cells (CR3/43). This analysis revealed that the large subpial lesions accounted for the majority of demyelinated cortex despite possessing the lowest density of inflammatory cells. This study has shown that lesions in this model share many of the major features of cortical lesions in MS both in terms of morphology and inflammatory cell content.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL090005-11
Application #
7332099
Study Section
(LDRR)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Anderson, Stasia A; Frank, Joseph A (2007) MRI of mouse models of neurological disorders. NMR Biomed 20:200-15
Pomeroy, Ian M; Matthews, Paul M; Frank, Joseph A et al. (2005) Demyelinated neocortical lesions in marmoset autoimmune encephalomyelitis mimic those in multiple sclerosis. Brain 128:2713-21
Anderson, Stasia A; Shukaliak-Quandt, Jacqueline; Jordan, Elaine K et al. (2004) Magnetic resonance imaging of labeled T-cells in a mouse model of multiple sclerosis. Ann Neurol 55:654-9
Bulte, Jeff W M; Ben-Hur, Tamir; Miller, Bradley R et al. (2003) MR microscopy of magnetically labeled neurospheres transplanted into the Lewis EAE rat brain. Magn Reson Med 50:201-5
Bulte, Jeff W M; Douglas, Trevor; Witwer, Brian et al. (2002) Monitoring stem cell therapy in vivo using magnetodendrimers as a new class of cellular MR contrast agents. Acad Radiol 9 Suppl 2:S332-5
Frank, Joseph A; Zywicke, Holly; Jordan, E K et al. (2002) Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol 9 Suppl 2:S484-7
Bulte, Jeff W M; Duncan, Ian D; Frank, Joseph A (2002) In vivo magnetic resonance tracking of magnetically labeled cells after transplantation. J Cereb Blood Flow Metab 22:899-907
McFarland, H I; Lobito, A A; Johnson, M M et al. (2001) Effective antigen-specific immunotherapy in the marmoset model of multiple sclerosis. J Immunol 166:2116-21
Bulte, J W; Douglas, T; Witwer, B et al. (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19:1141-7