TY - JOUR
T1 - Intravenous application of CD271-selected mesenchymal stem cells during fracture healing
AU - Dreger, Tina
AU - Watson, John T.
AU - Akers, Walter
AU - Molligan, Jeremy
AU - Achilefu, Samuel
AU - Schon, Lew C.
AU - Zhang, Zijun
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Mesenchymal stem cells
KW - fracture
KW - homing
KW - intravenous injection
KW - rats
UR - http://www.scopus.com/inward/record.url?scp=84897112105&partnerID=8YFLogxK
U2 - 10.1097/BOT.0000000000000063
DO - 10.1097/BOT.0000000000000063
M3 - Article
C2 - 24378433
AN - SCOPUS:84897112105
SN - 0890-5339
VL - 28
SP - S15-S19
JO - Journal of orthopaedic trauma
JF - Journal of orthopaedic trauma
IS - SUPPL. 1
ER -