title: Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model.
abstract: OBJECTIVE
  We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor-β3 [TGF-β3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could be combined immediately prior to implantation to induce a superior healing response in vivo relative to the hydrogel alone.
  
  
  METHODS
  Trochlear chondral defects were created in Yucatan mini-pigs (6 months old). Treatment groups included an HA hydrogel alone and hydrogels containing allogeneic MSCs, TGF-β3, or both. Six weeks after surgery, micro-computed tomography was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen.
  
  
  RESULTS
  Treatment with TGF-β3 led to a marked increase in positive staining for collagen type II within defects (P < 0.05), while delivery of MSCs did not (P > 0.05). Neither condition had an impact on other histological semiquantitative scores (P > 0.05), and inclusion of MSCs led to significantly less defect fill (P < 0.05). For all measurements, no synergistic interaction was found between TGF-β3 and MSC treatment when they were delivered together (P > 0.05).
  
  
  CONCLUSIONS
  At this early healing time point, treatment with TGF-β3 promoted the formation of collagen type II within the defect, while allogeneic MSCs had little benefit. Combination of TGF-β3 and MSCs at the time of surgery did not produce a synergistic effect. An in vitro precultured construct made of these components may be required to enhance in vivo repair in this model system.
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA; North Carolina State University, Raleigh, NC, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Fisher
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Belkin
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Milby
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Henning
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Söegaard
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Minwook
authors.initials: M
authors.lastname: Kim
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA; Department of Trauma Surgery, Regensburg University Medical Center, Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pfeifer
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Saxena
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Dodge
authors.affiliation: Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
authors.affiliation: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Schaer
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Steinberg
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
keywords: TGF-β3; animal models; cartilage; mesenchymal stem cells; repair