Intravenous application of CD271-selected mesenchymal stem cells during fracture healing

Tina Dreger, John T. Watson, Walter Akers, Jeremy Molligan, Samuel Achilefu, Lew C. Schon, Zijun Zhang

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Objectives: 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. Clinical relevance: Intravenous application of MSCs may serve as a practical route to deliver stem cells for the treatment of fracture nonunion and delayed union. Levels of evidence: Level I.

Original languageEnglish
Pages (from-to)S15-S19
JournalJournal of orthopaedic trauma
Volume28
Issue numberSUPPL. 1
DOIs
StatePublished - 2014

Keywords

  • Mesenchymal stem cells
  • fracture
  • homing
  • intravenous injection
  • rats

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