Sakai Daisuke, Nishimura Kazuhiro, Tanaka Masahiro, Nakajima Daisuke, Grad Sibylle, Alini Mauro, Kawada Hiroshi, Ando Kiyoshi, Mochida Joji
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan; Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan; AO Spine Research Network.
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
Spine J. 2015 Jun 1;15(6):1356-65. doi: 10.1016/j.spinee.2013.07.491. Epub 2014 Nov 24.
Mobilization and homing of bone marrow-derived cells (BMCs) play a pivotal role in healing and regeneration of various tissues. However, the cellular response of BMCs in avascular tissue such as the intervertebral disc (IVD) has not been studied in detail. One of the main obstacles to this is a lack of a suitable mouse disc degeneration model.
The purpose of this study was to establish a reproducible disc degeneration mouse model suitable for analyzing the cellular response of the disc microenvironment and to determine whether BMCs are recruited into the IVD.
An experimental animal study of disc degeneration investigating the potential of BMCs in an endogenous repair of the IVD.
We transplanted whole bone marrow cells from mice ubiquitously expressing enhanced green fluorescent protein into lethally irradiated mice. Intervertebral disc degeneration was induced through uneven loading by creating a loop in the tail of these mice. The vertebral bone-disc-vertebral bone units were harvested, and BMCs were identified by immunohistochemistry.
A new disc degeneration model was established in the mouse. Applying this model in the bone marrow chimeric mice increased the number of BMCs in the peripheral bone marrow and vascular canals in the endplate, and some were found in the IVD. The migration of BMCs was related to the severity of IVD degeneration.
Although providing a new disc degeneration model in mice, the present study provides evidence to suggest that although BMCs are recruited during disc degeneration, only a limited number of BMCs migrate to the IVD, presumably because of its avascular nature. This fact provides important elements for developing new treatments as many growth factors and compounds are being tested, both in investigational levels and clinical trials to nourish resident endogenous cells during the degenerative process.
骨髓来源细胞（BMCs）的动员和归巢在各种组织的愈合和再生中起关键作用。然而，BMCs在无血管组织如椎间盘（IVD）中的细胞反应尚未得到详细研究。其中一个主要障碍是缺乏合适的小鼠椎间盘退变模型。
本研究的目的是建立一个适用于分析椎间盘微环境细胞反应的可重复性椎间盘退变小鼠模型，并确定BMCs是否被募集到IVD中。
一项关于椎间盘退变的实验动物研究，调查BMCs在内源性修复IVD中的潜力。
我们将来自普遍表达增强型绿色荧光蛋白的小鼠的全骨髓细胞移植到经致死剂量照射的小鼠体内。通过在这些小鼠尾巴上制造一个环，通过不均匀加载诱导椎间盘退变。收集椎体-椎间盘-椎体单元，通过免疫组织化学鉴定BMCs。
在小鼠中建立了一种新的椎间盘退变模型。将该模型应用于骨髓嵌合小鼠，增加了终板外周骨髓和血管通道中BMCs的数量，并且在IVD中发现了一些BMCs。BMCs的迁移与IVD退变的严重程度相关。
尽管本研究提供了一种新的小鼠椎间盘退变模型，但有证据表明，尽管在椎间盘退变过程中BMCs被募集，但只有有限数量的BMCs迁移到IVD，这可能是由于其无血管的性质。这一事实为开发新的治疗方法提供了重要因素，因为目前在研究水平和临床试验中正在测试许多生长因子和化合物，以在退变过程中滋养驻留的内源性细胞。
