title: Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model.
abstract: Transplantation of pluripotent stem cells and their differentiated progeny has the potential to preserve or regenerate functional pathways and improve function after central nervous system injury. However, their utility has been hampered by poor survival and the potential to form tumors. Peptide-modified biomaterials influence cell adhesion, survival and differentiation in vitro, but their effectiveness in vivo remains uncertain. We synthesized a peptide-modified, minimally invasive, injectable hydrogel comprised of hyaluronan and methylcellulose to enhance the survival and differentiation of human induced pluripotent stem cell-derived oligodendrocyte progenitor cells. Cells were transplanted subacutely after a moderate clip compression rat spinal cord injury. The hydrogel, modified with the RGD peptide and platelet-derived growth factor (PDGF-A), promoted early survival and integration of grafted cells. However, prolific teratoma formation was evident when cells were transplanted in media at longer survival times, indicating that either this cell line or the way in which it was cultured is unsuitable for human use. Interestingly, teratoma formation was attenuated when cells were transplanted in the hydrogel, where most cells differentiated to a glial phenotype. Thus, this hydrogel promoted cell survival and integration, and attenuated teratoma formation by promoting cell differentiation.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, Canada M5S 3E5; Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ontario, Canada M5S 3E1.
authors.forename: T
authors.initials: T
authors.lastname: Führmann
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, Canada M5S 3E5; Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ontario, Canada M5S 3E1.
authors.forename: R Y
authors.initials: RY
authors.lastname: Tam
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ontario, Canada M5S 3E1.
authors.forename: B
authors.initials: B
authors.lastname: Ballarin
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Coles
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, Canada M5S 3E5; Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ontario, Canada M5S 3E1.
authors.forename: I
authors.initials: I
authors.lastname: Elliott Donaghue
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
authors.forename: D
authors.initials: D
authors.lastname: van der Kooy
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Krembil Neuroscience Centre, Toronto Western Research Institute, and Department of Surgery, University of Toronto, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8.
authors.forename: C H
authors.initials: CH
authors.lastname: Tator
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ontario, Canada M5S 3E1; Department of Surgery, University of Toronto, Donnelly Centre, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Morshead
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, Canada M5S 3E5; Institute of Biomaterials and Biomedical Engineering, 160 College Street, Room 530, Toronto, Ontario, Canada M5S 3E1. Electronic address: molly.shoichet@utoronto.ca.
authors.forename: M S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007267:Injections; D008747:Methylcellulose / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology* / Q000637:transplantation; D009842:Oligopeptides / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D013724:Teratoma / Q000473:pathology*
chemical_list: D009842:Oligopeptides; D010982:Platelet-Derived Growth Factor; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C047981:arginyl-glycyl-aspartic acid; D006820:Hyaluronic Acid; D008747:Methylcellulose
keywords: Cell adhesion molecules; Cell transplantation; Differentiation; Hydrogel; Induced pluripotent stem cells; Oligodendrocytes; Spinal cord injury