Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
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DOI：
10.1155/2019/5750967
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发表时间：
2019-01-01
影响因子：
4.3
通讯作者：
Liu, Lei
中科院分区：
文献类型：
--
作者：
Li, Jun;Huang, Zeyu;Liu, Lei
节段性骨缺损的重建对骨科临床医生和科学家都提出了巨大的挑战，因为骨修复是必要的，而且可能超出自我愈合的能力。骨髓间充质干细胞（BMSCs）具有较强的增殖能力，比成熟的成骨细胞更容易获得，是促进骨修复的最佳祖细胞来源。尽管BMSCs在再生医学，特别是骨重建方面具有潜力，但在BMSCs的先前应用中仍然存在值得注意的局限性，包括可以招募的细胞量，移植细胞的骨迁移受损，增殖和成骨细胞分化能力降低，以及可能的肿瘤发生。我们的研究表明，经尾静脉移植的骨髓间充质干细胞可被促红细胞生成素（EPO）动员到骨缺损区，参与新骨的再生。本研究的组织学分析和micro-CT结果显示，EPO可显著促进BMSCs体内成骨和血管生成效率。与单独的BMSC组和对照组相比，接受EPO+BMSC给药的动物表现出新骨形成、组织结构组织、新血管密度、骨痂形成和骨矿物质密度（BMD）的显著增加。在生物力学水平上，我们证明了EPO和BMSCs联合移植通过增加骨干的强度，使其不那么脆弱，从而增强了骨缺损的重建。因此，EPO联合BMSC移植可能成为节段性骨缺损修复的新策略。
Reconstruction of segmental bone defects poses a tremendous challenge for both orthopedic clinicians and scientists, since bone rehabilitation is requisite substantially and may be beyond the capacity of self-healing. Bone marrow mesenchymal stem cells (BMSCs) have been identified as an optimal progenitor cell source to facilitate bone repair since they have a higher ability for proliferation and are more easily accessible than mature osteoblastic cells. In spite of the potential of BMSCs in regeneration medicine, particularly for bone reconstruction, noteworthy limitations still remain in previous application of BMSCs, including the amount of cells that could be recruited, the compromised bone migration of grafted cells, reduced proliferation and osteoblastic differentiation ability, and likely tumorigenesis. Our current work demonstrates that BMSCs transplanted through the caudal vein can be mobilized by erythropoietin (EPO) to the bone defect area and participate in regeneration of new bone. Based on the histological analysis and micro-CT findings of this study, EPO can dramatically promote the effects on the osteogenesis and angiogenesis efficiency of BMSCs in vivo. Animals that underwent EPO+BMSC administration demonstrated a remarkable increase in new bone formation, tissue structure organization, new vessel density, callus formation, and bone mineral density (BMD) compared with the BMSCs alone and control groups. At the biomechanical level, we demonstrated that combing transplantation of EPO and BMSCs enhances bone defect reconstruction by increasing the strength of the diaphysis, making it less fragile. Therefore, combination therapy using EPO infusion and BMSC transplantation may be a new therapeutic strategy for the reconstruction of segmental bone defect.