title: Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.
abstract: Cell therapy with mesenchymal stem cells (MSCs) can improve tissue healing. It is possible, however, that priming MSCs prior to implantation can further enhance their therapeutic benefit. This study was then performed to test whether priming MSCs to be more anti-inflammatory would enhance healing in a rat ligament model, i.e. a medial collateral ligament (MCL). MSCs were primed for 48 h using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1 μg/ml. Rat MCLs were surgically transected and administered 1 × 10(6) cells in a carrier solution at the time of injury. A series of healing metrics were analyzed at days 4 and 14 post-injury in the ligaments that received primed MSCs, unprimed MSCs, or no cells (controls). Applying primed MSCs beneficially altered healing by affecting endothelialization, type 2 macrophage presence, apoptosis, procollagen 1α, and IL-1Ra levels. When analyzing MSC localization, both primed and unprimed MSCs co-localized with endothelial cells and pericytes suggesting a supportive role in angiogenesis. Priming MSCs prior to implantation altered key ligament healing events, resulted in a more anti-inflammatory environment, and improved healing.
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, 1111 Highland Ave, WIMR Room 5059, Madison, WI, 53705, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Saether
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53705, USA.
authors.forename: Connie S
authors.initials: CS
authors.lastname: Chamberlain
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, WI, 53705, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Leiferman
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53705, USA.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Brickson
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, 1111 Highland Ave, WIMR Room 5059, Madison, WI, 53705, USA. Vanderby@ortho.wisc.edu.|Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53705, USA. Vanderby@ortho.wisc.edu.
authors.forename: Ray
authors.initials: R
authors.lastname: Vanderby
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D017885:Collateral Ligaments / Q000098:blood supply / Q000293:injuries*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053590:Interleukin 1 Receptor Antagonist Protein; D011070:Poly I-C
keywords: Angiogenesis; Inflammation; Ligament; Macrophage; Mesenchymal stem cells; Polycytidylic acid