title: Mesenchymal stem cell-collagen microspheres for articular cartilage repair: cell density and differentiation status.
abstract: Mesenchymal stem cells (MSC) hold promise for cartilage repair. A microencapsulation technique was previously established to entrap MSC in collagen microspheres, and the collagen fibrous meshwork was found to be an excellent scaffold for supporting MSC survival, growth and differentiation. This study investigates the importance of cell density and differentiation status of MSC-collagen microspheres in cartilage repair. MSC were isolated from rabbit bone marrow and encapsulated in collagen microspheres. The effects of pre-differentiating the encapsulated MSC into chondrogenic lineages and different cell densities on cartilage repair were investigated in rabbits. Implantation of undifferentiated collagen-MSC microspheres formed hyaline-like cartilage rich in type II collagen and glycosaminoglycans (GAG) at 1month post-implantation. By 6months, hyaline cartilage rich in type II collagen and GAG, but negative for type I collagen, and partial zonal organization were found in both undifferentiated and chondrogenically differentiated groups in the high cell density group. The undifferentiated group and high cell density group significantly improved the O'Driscoll histological score. Moreover, the undifferentiated group significantly increased the GAG content. The mechanically differentiated group showed stiffer but thinner cartilage, while the undifferentiated group showed thicker but softer cartilage compared with their respective contra-lateral controls. This work suggests that a higher local cell density favors cartilage regeneration, regardless of the differentiation status of MSC, while the differentiation status of MSC does significantly affect regeneration outcomes.
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, Room 711, Haking Wong Building, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Li
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, Room 711, Haking Wong Building, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: H W
authors.initials: HW
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: K M C
authors.initials: KM
authors.lastname: Cheung
authors.affiliation: Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: D
authors.initials: D
authors.lastname: Chan
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, Room 711, Haking Wong Building, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region. Electronic address: bpchan@hku.hk.
authors.forename: B P
authors.initials: BP
authors.lastname: Chan
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008863:Microspheres; D011817:Rabbits; D051381:Rats; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen
keywords: Articular cartilage; Cell density; Collagen microsphere; Differentiation status; Mesenchymal stem cell