title: MHC mismatch inhibits neurogenesis and neuron maturation in stem cell allografts.
abstract: BACKGROUND
  The role of histocompatibility and immune recognition in stem cell transplant therapy has been controversial, with many reports arguing that undifferentiated stem cells are protected from immune recognition due to the absence of major histocompatibility complex (MHC) markers. This argument is even more persuasive in transplantation into the central nervous system (CNS) where the graft rejection response is minimal.
  
  
  RESULTS
  In this study, we evaluate graft survival and neuron production in perfectly matched vs. strongly mismatched neural stem cells transplanted into the hippocampus in mice. Although allogeneic cells survive, we observe that MHC-mismatch decreases surviving cell numbers and strongly inhibits the differentiation and retention of graft-derived as well as endogenously produced new neurons. Immune suppression with cyclosporine-A did not improve outcome but non-steroidal anti-inflammatory drugs, indomethacin or rosiglitazone, were able to restore allogeneic neuron production, integration and retention to the level of syngeneic grafts.
  
  
  CONCLUSIONS
  These results suggest an important but unsuspected role for innate, rather than adaptive, immunity in the survival and function of MHC-mismatched cellular grafts in the CNS.
authors.affiliation: Department of Neurosurgery, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford, California, United States of America.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.forename: Lori K
authors.initials: LK
authors.lastname: Phillips
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gould
authors.forename: Jay
authors.initials: J
authors.lastname: Campisi
authors.forename: Star W
authors.initials: SW
authors.lastname: Lee
authors.forename: Brandi K
authors.initials: BK
authors.lastname: Ormerod
authors.forename: Monika
authors.initials: M
authors.lastname: Zwierzchoniewska
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Martinez
authors.forename: Theo D
authors.initials: TD
authors.lastname: Palmer
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045142:Cross-Priming / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006624:Hippocampus / Q000166:cytology; D006650:Histocompatibility Testing; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016572:Cyclosporine