title: A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation.
abstract: The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.
authors.affiliation: Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Ballios
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cooke
authors.affiliation: Division of Ophthalmology, Department of Surgery, Faculty of Health Sciences, McMaster University, 2757 King Street East, Hamilton, ON L8G 4X3, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Donaldson
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Brenda L K
authors.initials: BL
authors.lastname: Coles
authors.affiliation: Department of Surgery, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Cindi M
authors.initials: CM
authors.lastname: Morshead
authors.affiliation: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada. Electronic address: derek.van.der.kooy@utoronto.ca.
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada. Electronic address: molly.shoichet@utoronto.ca.
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000818:Animals; D001766:Blindness / Q000235:genetics / Q000628:therapy / Q000662:veterinary; D002470:Cell Survival; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007150:Immunohistochemistry; D008747:Methylcellulose / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000166:cytology / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology; D012243:Rhodopsin / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D020521:Stroke / Q000139:chemically induced / Q000628:therapy / Q000662:veterinary
chemical_list: D018960:Hyaluronan Receptors; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D008747:Methylcellulose; D012243:Rhodopsin