title: Age-Independent Cartilage Generation for Synovium-Based Autologous Chondrocyte Implantation.
abstract: The articular cartilage layer of synovial joints is commonly lesioned by trauma or by a degenerative joint disease. Attempts to repair the damage frequently involve the performance of autologous chondrocyte implantation (ACI). Healthy cartilage must be first removed from the joint, and then, on a separate occasion, following the isolation of the chondrocytes and their expansion in vitro, implanted within the lesion. The disadvantages of this therapeutic approach include the destruction of healthy cartilage-which may predispose the joint to osteoarthritic degeneration-the necessarily restricted availability of healthy tissue, the limited proliferative capacity of the donor cells-which declines with age-and the need for two surgical interventions. We postulated that it should be possible to induce synovial stem cells, which are characterized by high, age-independent, proliferative and chondrogenic differentiation capacities, to lay down cartilage within the outer juxtasynovial space after the transcutaneous implantation of a carrier bearing BMP-2 in a slow-release system. The chondrocytes could be isolated on-site and immediately used for ACI. To test this hypothesis, Chinchilla rabbits were used as an experimental model. A collagenous patch bearing BMP-2 in a slow-delivery vehicle was sutured to the inner face of the synovial membrane. The neoformed tissue was excised 5, 8, 11 and 14 days postimplantation for histological and histomorphometric analyses. Neoformed tissue was observed within the outer juxtasynovial space already on the 5th postimplantation day. It contained connective and adipose tissues, and a central nugget of growing cartilage. Between days 5 and 14, the absolute volume of cartilage increased, attaining a value of 12 mm(3) at the latter juncture. Bone was deposited in measurable quantities from the 11th day onwards, but owing to resorption, the net volume did not exceed 1.5 mm(3) (14th day). The findings confirm our hypothesis. The quantity of neoformed cartilage that is deposited after only 1 week within the outer juxtasynovial space would yield sufficient cells for ACI. Since the BMP-2-bearing patches would be implanted transcutaneously in humans, only one surgical or arthroscopic intervention would be called for. Moreover, most importantly, sufficient numbers of cells could be generated in patients of all ages.
authors.affiliation: Departments of Osteoporosis, Orthopaedic Surgery and Clinical Research, Center of Regenerative Medicine for Skeletal Tissues, Inselspital, University of Bern , Bern, Switzerland .
authors.forename: Ernst B
authors.initials: EB
authors.lastname: Hunziker
authors.affiliation: Departments of Osteoporosis, Orthopaedic Surgery and Clinical Research, Center of Regenerative Medicine for Skeletal Tissues, Inselspital, University of Bern , Bern, Switzerland .
authors.forename: Kurt
authors.initials: K
authors.lastname: Lippuner
authors.affiliation: Departments of Osteoporosis, Orthopaedic Surgery and Clinical Research, Center of Regenerative Medicine for Skeletal Tissues, Inselspital, University of Bern , Bern, Switzerland .
authors.forename: Marius J B
authors.initials: MJ
authors.lastname: Keel
authors.affiliation: Departments of Osteoporosis, Orthopaedic Surgery and Clinical Research, Center of Regenerative Medicine for Skeletal Tissues, Inselspital, University of Bern , Bern, Switzerland .
authors.forename: Nahoko
authors.initials: N
authors.lastname: Shintani
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000502:physiology*; D019902:Chondrocytes / Q000187:drug effects / Q000637:transplantation*; D005260:Female; D007719:Knee Joint / Q000187:drug effects / Q000601:surgery; D008297:Male; D009928:Organ Specificity / Q000187:drug effects; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects / Q000502:physiology*; D014182:Transplantation, Autologous
chemical_list: D055396:Bone Morphogenetic Protein 2