title: Immune modulation with primed mesenchymal stem cells delivered via biodegradable scaffold to repair an Achilles tendon segmental defect.
abstract: Tendon healing is a complex coordinated series of events resulting in protracted recovery, limited regeneration, and scar formation. Mesenchymal stem cell (MSC) therapy has shown promise as a new technology to enhance soft tissue and bone healing. A challenge with MSC therapy involves the ability to consistently control the inflammatory response and subsequent healing. Previous studies suggest that preconditioning MSCs with inflammatory cytokines, such as IFN-γ, TNF-α, and IL-1β may accelerate cutaneous wound closure. The objective of this study was to therefore elucidate these effects in tendon. That is, the in vivo healing effects of TNF-α primed MSCs were studied using a rat Achilles segmental defect model. Rat Achilles tendons were subjected to a unilateral 3 mm segmental defect and repaired with either a PLG scaffold alone, MSC-seeded PLG scaffold, or TNF-α-primed MSC-seeded PLG scaffold. Achilles tendons were analyzed at 2 and 4 weeks post-injury. In vivo, MSCs, regardless of priming, increased IL-10 production and reduced the inflammatory factor, IL-1α. Primed MSCs reduced IL-12 production and the number of M1 macrophages, as well as increased the percent of M2 macrophages, and synthesis of the anti-inflammatory factor IL-4. Primed MSC treatment also increased the concentration of type I procollagen in the healing tissue and increased failure stress of the tendon 4 weeks post-injury. Taken together delivery of TNF-α primed MSCs via 3D PLG scaffold modulated macrophage polarization and cytokine production to further accentuate the more regenerative MSC-induced healing response. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:269-280, 2017.
authors.affiliation: Department of Orthopedics, Ankara Oncology Research and Training Hospital, Ankara, Turkey.
authors.forename: Erdem
authors.initials: E
authors.lastname: Aktas
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Connie S
authors.initials: CS
authors.lastname: Chamberlain
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Saether
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Duenwald-Kuehl
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Kondratko-Mittnacht
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Michael
authors.initials: M
authors.lastname: Stitgen
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Clements
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, 53705.|Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: William L
authors.initials: WL
authors.lastname: Murphy
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, 53705.|Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, 53705.
authors.forename: Ray
authors.initials: R
authors.lastname: Vanderby
mesh_terms: D000125:Achilles Tendon / Q000293:injuries; D000818:Animals; D045164:Mesenchymal Stem Cell Transplantation; D011916:Rats, Inbred F344; D013708:Tendon Injuries / Q000628:therapy*; D054457:Tissue Scaffolds; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Achilles; MSC; TNF-α; priming; tendon healing