title: hESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation.
abstract: Stem cell therapies for neurological disorders are rapidly moving towards use in clinical trials. Before initiation of clinical trials, extensive pre-clinical validation in appropriate animal models is essential. However, grafts of human cells into the rodent brain are rejected within weeks after transplantation and the standard methods of immune-suppression for the purpose of studying human xenografts are not always sufficient for the long-term studies needed for transplanted human neurons to maturate, integrate and provide functional benefits in the host brain. Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their immune system. Here, we show that differentiated human embryonic stem cells (hESCs) can be used for desensitisation to achieve long-term graft survival of human stem cell-derived neurons in a xenograft setting, surpassing the time of conventional pharmacological immune-suppressive treatments. The use of hESCs for desensitisation opens up for a widespread use of the technique, which will be of great value when performing pre-clinical evaluation of stem cell-derived neurons in animal models.
authors.affiliation: Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heuer
authors.affiliation: Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Human Neural Development, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
authors.forename: Agnete
authors.initials: A
authors.lastname: Kirkeby
authors.affiliation: Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfisterer
authors.affiliation: Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Jönsson
authors.affiliation: Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden. Electronic address: malin.parmar@med.lu.se.
authors.forename: Malin
authors.initials: M
authors.lastname: Parmar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001930:Brain Injuries / Q000139:chemically induced / Q000276:immunology / Q000601:surgery*; D002461:Cell Line, Transformed; D016572:Cyclosporine / Q000494:pharmacology; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013565:Sympatholytics / Q000633:toxicity; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D015703:Antigens, CD; D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D013565:Sympatholytics; D049452:Green Fluorescent Proteins; D016572:Cyclosporine; D016627:Oxidopamine
keywords: Cyclosporine; Desensitisation; Immune response; Rejection; Stem cell; Transplant; Xenograft; hESC