title: Encapsulation of allogeneic mesenchymal stem cells in alginate extends local presence and therapeutic function.
abstract: Bone marrow derived mesenchymal stem cells (MSCs) have immunomodulatory and trophic capacities. For therapeutic application in local chronic inflammatory diseases, MSCs, preferably of allogeneic origin, have to retain immunomodulatory properties. This might be achieved by encapsulation of MSCs in a biomaterial that protects them from the host immune system. Most studies investigating the properties of MSCs for therapeutic application use short term cultures of cells in monolayer. Since the physical environment of MSCs can influence their functionality, we evaluated the feasibility of preserving the immunomodulatory properties of MSCs encapsulated in a three-dimensional alginate construct. After 5 weeks of implantation in immunocompetent rats, active allogeneic MSCs encapsulated in alginate were still detectable by Bio Luminescence Imaging and Magnetic Resonance Imaging of luciferase transduced and superparamagnetic iron oxide labelled MSCs. MSCs injected in saline were only detectable up to 1 week after injection. Moreover, the MSCs encapsulated in alginate responded to inflammatory stimuli similarly to MSCs in monolayer culture. In addition, MSC-alginate beads secreted immunomodulatory and trophic factors and inhibited T-cell proliferation after 30 d of in vitro culture. Our data indicate that allogeneic MSCs encapsulated in alginate persist locally and could act as an interactive immunomodulatory or trophic factor release system for several weeks, making this an interesting system to investigate for application in inflammatory disease conditions.
authors.forename: M J
authors.initials: MJ
authors.lastname: Leijs
authors.forename: E
authors.initials: E
authors.lastname: Villafuertes
authors.forename: J C
authors.initials: JC
authors.lastname: Haeck
authors.forename: W J
authors.initials: WJ
authors.lastname: Koevoet
authors.forename: B
authors.initials: B
authors.lastname: Fernandez-Gutierrez
authors.forename: M J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.forename: J A
authors.initials: JA
authors.lastname: Verhaar
authors.forename: M R
authors.initials: MR
authors.lastname: Bernsen
authors.forename: G M
authors.initials: GM
authors.lastname: van Buul
authors.affiliation: Department of Orthopaedics and Department of Otorhinolaryngology, Room Ee1655, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.g.vanosch@erasmusmc.nl.
authors.forename: G J
authors.initials: GJ
authors.lastname: van Osch
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D007121:Immunocompetence / Q000187:drug effects; D056747:Immunomodulation / Q000187:drug effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D017208:Rats, Wistar; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D000464:Alginates; D017077:Culture Media, Conditioned; D006603:Hexuronic Acids; D020723:Glucuronic Acid