Tina Dreger1, John T Watson, Walter Akers, Jeremy Molligan, Samuel Achilefu, Lew C Schon, Zijun Zhang. 1. *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.
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.
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 immunodeficientmice. 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.
Authors: Jessica J Alm; Helka M A Koivu; Terhi J Heino; Teuvo A Hentunen; Saara Laitinen; Hannu T Aro Journal: J Orthop Res Date: 2010-12 Impact factor: 3.494
Authors: Samuel Achilefu; Sharon Bloch; Mary A Markiewicz; Tuoxiu Zhong; Yunpeng Ye; Richard B Dorshow; Britton Chance; Kexian Liang Journal: Proc Natl Acad Sci U S A Date: 2005-05-23 Impact factor: 11.205
Authors: Froilán Granero-Moltó; Jared A Weis; Michael I Miga; Benjamin Landis; Timothy J Myers; Lynda O'Rear; Lara Longobardi; E Duco Jansen; Douglas P Mortlock; Anna Spagnoli Journal: Stem Cells Date: 2009-08 Impact factor: 6.277
Authors: Chris L Smith; Kaisorn L Chaichana; Young M Lee; Benjamin Lin; Kevin M Stanko; Thomas O'Donnell; Saksham Gupta; Sagar R Shah; Joanne Wang; Olindi Wijesekera; Michael Delannoy; Andre Levchenko; Alfredo Quiñones-Hinojosa Journal: Stem Cells Transl Med Date: 2015-02-02 Impact factor: 6.940
Authors: Kang I Ko; Leila S Coimbra; Chen Tian; Jazia Alblowi; Rayyan A Kayal; Thomas A Einhorn; Louis C Gerstenfeld; Robert J Pignolo; Dana T Graves Journal: Diabetologia Date: 2015-01-07 Impact factor: 10.122
Authors: Claudia Schlundt; Christian H Bucher; Serafeim Tsitsilonis; Hanna Schell; Georg N Duda; Katharina Schmidt-Bleek Journal: Curr Osteoporos Rep Date: 2018-04 Impact factor: 5.096
Authors: Cameron R M Black; Vitali Goriainov; David Gibbs; Janos Kanczler; Rahul S Tare; Richard O C Oreffo Journal: Curr Mol Biol Rep Date: 2015-08-15