title: Intravenous application of CD271-selected mesenchymal stem cells during fracture healing.
abstract: OBJECTIVE
  Circulating mesenchymal stem cells (MSCs) participate in fracture healing and can be used to enhance fracture healing. This study investigated how CD271-selected MSCs travel in circulation and when is the optimal time to apply MSCs intravenously during fracture healing.
  
  
  METHODS
  Based on the expression of CD271, MSCs were isolated from human bone marrow and labeled with cypate, a near-infrared fluorochrome. A unilateral closed fracture was created at the femur in immunodeficient mice. The cypate-labeled MSCs were injected into the tail vein of the mice at days 1 and 3 after fracture and were tracked by near-infrared imaging. The mice were euthanized at 3 weeks after fracture. Immunohistochemistry was performed to detect human MSCs at the fracture sites. Migration of CD271-selected MSCs, under the influence of stem cell-derived factor-1, was assessed in vitro.
  
  
  RESULTS
  Intravenously injected at day 1, but not day 3, after fracture, CD271-selected MSCs accumulated at the fracture sites significantly and lasted for at least 7 days. All fractures, with or without MSC injections, healed in 3 weeks. Human cells were localized at the fracture sites in mice by immunohistochemistry. CD271-selected MSCs migrated toward the medium contained stem cell-derived factor-1 in vitro.
  
  
  CONCLUSIONS
  After intravenous injection, CD271-selected MSCs were recruited to the fracture sites. The stages of fracture healing influenced the homing of culture-expanded MSCs. In mice, an optimal window of intravenous injection of MSCs was around 24 hours after fracture.
  
  
  CONCLUSIONS
  Intravenous application of MSCs may serve as a practical route to deliver stem cells for the treatment of fracture nonunion and delayed union.
authors.affiliation: *Department of Orthopaedic Surgery, Saint Louis University School of Medicine, St Louis, MO; †Department of Radiology, Washington University in St Louis School of Medicine, St Louis, MO; and ‡Orthobiologic Laboratory, MedStar Union Memorial Hospital, Baltimore, MD.
authors.forename: Tina
authors.initials: T
authors.lastname: Dreger
authors.forename: John T
authors.initials: JT
authors.lastname: Watson
authors.forename: Walter
authors.initials: W
authors.lastname: Akers
authors.forename: Jeremy
authors.initials: J
authors.lastname: Molligan
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.forename: Lew C
authors.initials: LC
authors.lastname: Schon
authors.forename: Zijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000068816:Adapalene; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000503:physiopathology* / Q000628:therapy*; D017102:Fracture Healing / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009281:Naphthalenes; D019265:Spectroscopy, Near-Infrared
chemical_list: D002352:Carrier Proteins; D009281:Naphthalenes; C548534:Sddr protein, mouse; D000068816:Adapalene