title: Autologous Bone Marrow Concentrate in a Sheep Model of Osteoarthritis: New Perspectives for Cartilage and Meniscus Repair.
abstract: Cell-based therapies are becoming a valuable tool to treat osteoarthritis (OA). This study investigated and compared the regenerative potential of bone marrow concentrate (BMC) and mesenchymal stem cells (MSC), both engineered with Hyaff(®)-11 (HA) for OA treatment in a sheep model.
  
  
  
  OA was induced via unilateral medial meniscectomy. Bone marrow was aspirated from the iliac crest, followed by concentration processes or cell isolation and expansion to obtain BMC and MSC, respectively. Treatments consisted of autologous BMC and MSC seeded onto HA. The regenerative potential of bone, cartilage, menisci, and synovia was monitored using macroscopy, histology, immunohistochemistry, and micro-computed tomography at 12 weeks post-op. Data were analyzed using the general linear model with adjusted Sidak's multiple comparison and Spearman's tests.
  
  
  
  BMC-HA treatment showed a greater repair ability in inhibiting OA progression compared to MSC-HA, leading to a reduction of inflammation in cartilage, meniscus, and synovium. Indeed, the decrease of inflammation positively contributed to counteract the progression of fibrotic and hypertrophic processes, known to be involved in tissue failure. Moreover, the treatment with BMC-HA showed the best results in allowing meniscus regeneration. Minor healing effects were noticed at bone level for both cell strategies; however, a downregulation of subchondral bone thickness (Cs.Th) was found in both cell treatments compared to the OA group in the femur.
  
  
  
  The transplantation of BMC-HA provided the best effects in supporting regenerative processes in cartilage, meniscus, and synovium and at less extent in bone. On the whole, both MSC and BMC combined with HA reduced inflammation and contributed to switch off fibrotic and hypertrophic processes. The observed regenerative potential by BMC-HA on meniscus could open new perspectives, suggesting its use not only for OA care but also for the treatment of meniscal lesions, even if further analyses are necessary to confirm its healing potential at long-term follow-up.
authors.affiliation: 1 Laboratory RAMSES, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Giovanna
authors.initials: G
authors.lastname: Desando
authors.affiliation: 2 Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute , Bologna, Italy .|3 Laboratory BITTA, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giavaresi
authors.affiliation: 1 Laboratory RAMSES, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Carola
authors.initials: C
authors.lastname: Cavallo
authors.affiliation: 4 Laboratory of Immunorheumatology and Tissue Regeneration, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Isabella
authors.initials: I
authors.lastname: Bartolotti
authors.affiliation: 1 Laboratory RAMSES, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Federica
authors.initials: F
authors.lastname: Sartoni
authors.affiliation: 2 Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute , Bologna, Italy .|3 Laboratory BITTA, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Nicolò
authors.initials: N
authors.lastname: Nicoli Aldini
authors.affiliation: 2 Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute , Bologna, Italy .|3 Laboratory BITTA, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Lucia
authors.initials: L
authors.lastname: Martini
authors.affiliation: 3 Laboratory BITTA, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Annapaola
authors.initials: A
authors.lastname: Parrilli
authors.affiliation: 4 Laboratory of Immunorheumatology and Tissue Regeneration, Rizzoli Orthopedic Institute , Bologna, Italy .|5 Department of Medical and Surgical Science, University of Bologna , Bologna, Italy .
authors.forename: Erminia
authors.initials: E
authors.lastname: Mariani
authors.affiliation: 2 Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute , Bologna, Italy .|3 Laboratory BITTA, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
authors.affiliation: 1 Laboratory RAMSES, Rizzoli Orthopedic Institute , Bologna, Italy .|4 Laboratory of Immunorheumatology and Tissue Regeneration, Rizzoli Orthopedic Institute , Bologna, Italy .
authors.forename: Brunella
authors.initials: B
authors.lastname: Grigolo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002357:Cartilage Diseases / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D000072600:Meniscus; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010003:Osteoarthritis / Q000473:pathology / Q000628:therapy*; D012038:Regeneration / Q000502:physiology*; D012756:Sheep; D054457:Tissue Scaffolds