title: Novel organ-slice culturing system to simulate meniscal repair: Proof of concept using a synovium-based pool of meniscoprogenitor cells.
abstract: Meniscal injuries can occur secondary to trauma or be instigated by the changes in knee-joint function that are associated with aging, osteo- and rheumatoid arthritis, disturbances in gait, and obesity. Sixty percent of persons over 50 years of age manifest signs of meniscal pathology. The surgical and arthroscopic measures that are currently implemented to treat meniscal deficiencies bring only transient relief from pain and effect but a temporary improvement in joint function. Although tissue-engineering-based approaches to meniscal repair are now being pursued, an appropriate in-vitro model has not been conceived. The aim of this study was to develop an organ-slice culturing system to simulate the repair of human meniscal lesions in vitro. The model consists of a ring of bovine meniscus enclosing a chamber that represents the defect and reproduces its sequestered physiological microenvironment. The defect, which is closed with a porous membrane, is filled with fragments of synovial tissue, as a source of meniscoprogenitor cells, and a fibrin-embedded, calcium-phosphate-entrapped depot of the meniscogenic agents BMP-2 and TGF-β1. After culturing for 2 to 6 weeks, the constructs were evaluated histochemically and histomorphometrically, as well as immunohistochemically, for the apoptotic marker caspase 3 and collagen types I and II. Under the defined conditions, the fragments of synovium underwent differentiation into meniscal tissue, which bonded with the parent meniscal wall. Both the parent and the neoformed meniscal tissue survived the duration of the culturing period without significant cell losses. The concept on which the in-vitro system is based was thus validated. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1588-1596, 2016.
authors.affiliation: Department of Osteoporosis, Inselspital, University of Bern, Bern, Switzerland.|Orthopaedic Surgery, Inselspital, University of Bern, Bern, Switzerland.|Clinical Research, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Ernst B
authors.initials: EB
authors.lastname: Hunziker
authors.affiliation: Department of Osteoporosis, Inselspital, University of Bern, Bern, Switzerland.|Clinical Research, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Kurt
authors.initials: K
authors.lastname: Lippuner
authors.affiliation: Orthopaedic Surgery, Inselspital, University of Bern, Bern, Switzerland.|Clinical Research, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Marius J B
authors.initials: MJ
authors.lastname: Keel
authors.affiliation: Department of Osteoporosis, Inselspital, University of Bern, Bern, Switzerland.|Orthopaedic Surgery, Inselspital, University of Bern, Bern, Switzerland.|Clinical Research, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Nahoko
authors.initials: N
authors.lastname: Shintani
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D000072600:Meniscus / Q000502:physiology*; D009924:Organ Culture Techniques; D012038:Regeneration; D013583:Synovial Membrane / Q000166:cytology*
keywords: in-vitro model; meniscus; organ slice; repair; tissue engineering