title: Local control of the host immune response performed with mesenchymal stem cells: perspectives for functional intracerebral xenotransplantation.
abstract: Foetal pig neuroblasts are interesting candidates as a cell source for transplantation, but xenotransplantation in the brain requires the development of adapted immunosuppressive treatments. As systemic administration of high doses of cyclosporine A has side effects and does not protect xenotransplants forever, we focused our work on local control of the host immune responses. We studied the advantage of cotransplanting syngenic mesenchymal stem cells (MSC) with porcine neuroblasts (pNb) in immunocompetent rat striata. Two groups of animals were transplanted, either with pNb alone or with both MSC and pNb. At day 63, no porcine neurons were detected in the striata that received only pNb, while four of six rats transplanted with both pNb and MSC exhibited healthy porcine neurons. Interestingly, 50% of the cotransplanted rats displayed healthy grafts with pNF70+ and TH+ neurons at 120 days post-transplantation. qPCR analyses revealed a general dwindling of pro- and anti-inflammatory cytokines in the striata that received the cotransplants. Motor recovery was also observed following the transplantation of pNb and MSC in a rat model of Parkinson's disease. Taken together, the present data indicate that the immunosuppressive properties of MSC are of great interest for the long-term survival of xenogeneic neurons in the brain.
authors.affiliation: INSERM, UMR 1064, Nantes, France; CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France; Faculté de Médecine, Université de Nantes, LUNAM Université, Nantes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Lévêque
authors.forename: Elodie
authors.initials: E
authors.lastname: Mathieux
authors.forename: Véronique
authors.initials: V
authors.lastname: Nerrière-Daguin
authors.forename: Reynald
authors.initials: R
authors.lastname: Thinard
authors.forename: Laetitia
authors.initials: L
authors.lastname: Kermarrec
authors.forename: Tony
authors.initials: T
authors.lastname: Durand
authors.forename: Thomas
authors.initials: T
authors.lastname: Haudebourg
authors.forename: Bernard
authors.initials: B
authors.lastname: Vanhove
authors.forename: Laurent
authors.initials: L
authors.lastname: Lescaudron
authors.forename: Isabelle
authors.initials: I
authors.lastname: Neveu
authors.forename: Philippe
authors.initials: P
authors.lastname: Naveilhan
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology*; D039481:CD11b Antigen / Q000378:metabolism; D002470:Cell Survival; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology; D007109:Immunity; D007111:Immunity, Cellular; D007121:Immunocompetence; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008969:Molecular Sequence Data; D009043:Motor Activity; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D016627:Oxidopamine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D034421:Sus scrofa; D014183:Transplantation, Heterologous
chemical_list: D039481:CD11b Antigen; D018925:Chemokines; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D016627:Oxidopamine
keywords: Parkinson; T cells; brain transplantation; immunosuppression; mesenchymal stem cells; rejection; restorative strategies; survival