title: Effect of Intra-Medullar and Intra-Venous Infusions of Mesenchymal Stem Cells on Cell Engraftment byIn-VivoCell Tracking and Osteoinductivity in Rabbit Long Bones: A Pilot Study.
abstract: OBJECTIVE
  Stem cell therapy can be an efficacious treatment option for bone fragility disorders (eg, osteogenesis imperfecta, disuse osteopenia, and osteoporosis), and successful cell therapy application may be dependent on optimal cell engraftment in target bones. The objective of this study was to compare the efficiency of intra-medullar and intra-venous delivery of mesenchymal stem cells (MSC) to improve cell engraftment rate, bone mineral density, and micro-architecture.
  
  
  METHODS
  By using six healthy juvenile New Zealand White rabbits, MSC were isolated from cancellous bone harvests and confirmed to have osteogenic capacity by inducing ectopic bone formation. The MSC were cultured, transduced by foamy viral vectors with marker genes for in vivo cell tracking, and expanded. All rabbits had one randomly selected limb receive intra-medullar infusion of 3×107to 1×108autologous MSC in the distal femur or the distal femur and proximal tibia. Two of six rabbits also received an intra-venous MSC infusion. At 28 days, MSC bone engraftment was assessed by PCR and the bone density and microstructure assessed by computed tomography and histomorphometry.
  
  
  RESULTS
  The intra-medullar-infused MSC were detected in epiphysis or diaphysis of the distal femurs and/or proximal tibiae. Infused MSC comprised 0.01 to 0.3% of all cells in the bone tissues. The intra-venous-infused MSC were not detected in any location. Neither intra-medullar nor intra-venous MSC infusion altered bone volume, bone mineral density, or cortical bone porosity/thickness. Systemic biodistribution of intra-medullar-infused MSC was not evident.
  
  
  CONCLUSIONS
  Our results indicated that intra-medullar infusion can be an effective cell delivery route for stem cell therapy potentially for orthopedic disorders, in preference to systemic administration. Further research is warranted to demonstrate an efficacy of intra-medullar MSC infusion on bone density and micro-architecture using animal models of bone disorders.
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Akikazu
authors.initials: A
authors.lastname: Ishihara
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohmine
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Weisbrode
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Bertone
keywords: Biodistribution; Bone fragility disorder; Cell engraftment; Intra-venous infusion; Intramedullar infusion; Mesenchymal stem cells; Rabbit