Dreger Tina, Watson John T, Akers Walter, Molligan Jeremy, Achilefu Samuel, Schon Lew C, Zhang Zijun
*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.
J Orthop Trauma. 2014;28 Suppl 1(0 1):S15-9. doi: 10.1097/BOT.0000000000000063.
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.
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.
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.
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.
Intravenous application of MSCs may serve as a practical route to deliver stem cells for the treatment of fracture nonunion and delayed union.
循环间充质干细胞（MSC）参与骨折愈合，可用于促进骨折愈合。本研究探讨了经CD271筛选的MSC在循环中的运行方式以及骨折愈合过程中静脉注射MSC的最佳时机。
基于CD271的表达，从人骨髓中分离出MSC，并用近红外荧光染料环孢素进行标记。在免疫缺陷小鼠的股骨上制造单侧闭合性骨折。在骨折后第1天和第3天，将环孢素标记的MSC注入小鼠尾静脉，并通过近红外成像进行追踪。骨折后3周对小鼠实施安乐死。进行免疫组织化学检测骨折部位的人MSC。在体外评估经CD271筛选的MSC在干细胞衍生因子-1影响下的迁移情况。
在骨折后第1天而非第3天静脉注射后，经CD271筛选的MSC在骨折部位显著聚集，并持续至少7天。所有骨折，无论是否注射MSC，均在3周内愈合。通过免疫组织化学在小鼠骨折部位检测到人类细胞。经CD271筛选的MSC在体外向含有干细胞衍生因子-1的培养基迁移。
静脉注射后，经CD271筛选的MSC被募集到骨折部位。骨折愈合阶段影响培养扩增的MSC的归巢。在小鼠中，静脉注射MSC的最佳窗口约为骨折后24小时。
静脉应用MSC可能是为治疗骨折不愈合和延迟愈合输送干细胞的一种实用途径。
