title: Noninvasive monitoring of immunosuppressive drug efficacy to prevent rejection of intracerebral glial precursor allografts.
abstract: The development of cell-based therapies opens up new avenues for treating a myriad of diseases of the central nervous system (CNS). While significant effort is being directed toward development of patient-specific, autologous transplantable cells, at present, the majority of cell transplantation  studies performed clinically utilize allografts. In this context, the issue of graft rejection and immunoprotection is of key importance. In this study, we transplanted mouse glial-restricted progenitors into immunodeficient, immunocompetent, and immunosuppressed mice and monitored their survival  noninvasively using bioluminescence imaging (BLI). With the use of serial BLI, we evaluated both the prevalence and dynamics of cell rejection. We demonstrate that allografts in immunocompetent mice were rejected at a rate of 69.2% (n = 13) indicating that graft tolerance is possible  even without immunosuppression. Immunosuppression using a combination of rapamycin and FK506 or cyclosporin failed to fully protect the grafts. FK506 and rapamycin treatment resulted in a slight improvement of immunoprotection (22.2% rejected, n = 9) compared to cyclosporin A (55.6%  rejected, n = 9); however, the difference was not significant. Notably, immunohistochemistry revealed leukocytes infiltrating the graft area in both rejecting and nonrejecting immunocompetent animals, but not in immunodeficient animals. The induction of an inflammatory process, even  in surviving allografts, has implications for their long-term survival and functionality.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gorelik
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Janowski
authors.forename: Chulani
authors.initials: C
authors.lastname: Galpoththawela
authors.forename: Robert
authors.initials: R
authors.lastname: Rifkin
authors.forename: Michael
authors.initials: M
authors.lastname: Levy
authors.forename: Barbara
authors.initials: B
authors.lastname: Lukomska
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kerr
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.forename: Piotr
authors.initials: P
authors.lastname: Walczak
mesh_terms: D000818:Animals; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009457:Neuroglia / Q000276:immunology / Q000637:transplantation*
chemical_list: D007166:Immunosuppressive Agents