Superior Potential of CD34-Positive Cells Compared to Total Mononuclear Cells for Healing of Nonunion Following Bone Fracture
Superior Potential of CD34-Positive Cells Compared to Total Mononuclear Cells for Healing of Nonunion Following Bone Fracture
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DOI：
10.3727/096368914x681586
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发表时间：
2015-01-01
影响因子：
3.3
通讯作者：
Asahara, Takayuki
中科院分区：
文献类型：
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作者：
Fukui, Tomoaki;Mifune, Yutaka;Asahara, Takayuki
我们最近证实，局部移植人外周血（PB）CD 34（+）细胞，一种内皮/造血祖细胞丰富的人口，有助于骨折修复通过血管生成/血管生成和骨生成。人PB单核细胞（MNC）也被认为是新血管形成的潜在细胞部分。我们以前已经证明了人PB MNCs促进骨折愈合的可行性。然而，目前还没有直接比较CD 34（+）细胞和MNCs之间的骨折修复效果的报道。此外，在我们以前的研究中使用了一种不愈合的骨折模型，该模型与临床环境不完全相似。为了克服这些问题，我们比较了人粒细胞集落刺激因子动员的PB（GM-PB）CD 34（+）细胞和人GM-PB MNCs在骨不连模型中的能力，该模型更接近于临床环境。首先，比较了局部移植1 × 105个GM-PB CD 34细胞（CD 34（+）组）、1 × 107个GM-PB MNC（含有约1 × 105个GM-PB CD 34（+）细胞）（MNC组）和磷酸盐缓冲盐水（PBS）（PBS组）对骨不连愈合的影响。在CD 34和MNC组中观察到了类似的会阴愈合部位血流恢复的增加。同时，通过影像学、组织学和功能评估显示，与其他组相比，CD 34组的骨不连修复效果上级。此外，通过体内和体外实验，证实了GM-PB MNCs诱导的过度炎症，并认为这是导致这种效力差异的机制之一。这些结果表明，局部移植GM-PB CD 34（+）细胞是治疗骨折后骨不连的一种实用而有效的策略。
We recently demonstrated that the local transplantation of human peripheral blood (PB) CD34(+) cells, an endothelial/hematopoietic progenitor cell-rich population, contributes to fracture repair via vasculogenesis/angiogenesis and osteogenesis. Human PB mononuclear cells (MNCs) are also considered a potential cell fraction for neovascularization. We have previously shown the feasibility of human PB MNCs to enhance fracture healing. However, there is no report directly comparing the efficacy for fracture repair between CD34(+) cells and MNCs. In addition, an unhealing fracture model, which does not accurately resemble a clinical setting, was used in our previous studies. To overcome these issues, we compared the capacity of human granulocyte colony-stimulating factor-mobilized PB (GM-PB) CD34(+) cells and human GM-PB MNCs in a nonunion model, which more closely resembles a clinical setting. First, the effect of local transplantation of 1 x 10(5) GM-PB CD34 cells (CD34(+) group), 1 x 10(7) GM-PB MNCs (containing approximately 1 x 10(5) GM-PB CD34(+) cells) (MNC group), and phosphate-buffered saline (PBS) (PBS group) on nonunion healing was compared. Similar augmentation of blood flow recovery at perinonunion sites was observed in the CD34 and MNC groups. Meanwhile, a superior effect on nonunion repair was revealed by radiological, histological, and functional assessment in the CD34 group compared with the other groups. Moreover, through in vivo and in vitro experiments, excessive inflammation induced by GM-PB MNCs was confirmed and believed to be one of the mechanisms underlying this potency difference. These results strongly suggest that local transplantation of GM-PB CD34(+) cells is a practical and effective strategy for treatment of nonunion after fracture.