Amelioration of a mouse model of osteogenesis imperfecta with hematopoietic stem cell transplantation: microcomputed tomography studies.
Amelioration of a mouse model of osteogenesis imperfecta with hematopoietic stem cell transplantation: microcomputed tomography studies.
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DOI：
10.1016/j.exphem.2010.04.008
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发表时间：
2010-07
影响因子：
2.6
通讯作者：
LaRue, Amanda C.
中科院分区：
文献类型：
--
作者：
Mehrotra, Meenal;Rosol, Michael;Ogawa, Makio;LaRue, Amanda C.
目的 在成骨不全症 (OI) 小鼠模型中检验造血干细胞 (HSC) 通过骨髓 (BM) 细胞移植产生骨细胞的假设。成骨不全症是一种由 I 型胶原蛋白数量和/或结构异常引起的遗传性疾病，其特征是骨质减少、骨骼脆弱和骨骼畸形。纯合 OI 小鼠（oim；B6C3Fe a/a-Col1a2oim/J）是正常 HSC 移植的优秀受体，因为骨祖细胞的快速周转已被证明。我们将来自转基因增强型绿色荧光蛋白（EGFP）小鼠的骨髓单核细胞或高度富集HSC的50个骨髓细胞移植到受辐射的oim小鼠中，并使用纵向微计算机断层扫描（micro-CT）分析骨参数的变化。移植后 3 至 6 个月，当小鼠表现出高水平的造血移植时，这些骨骼的 3D 显微 CT 图像观察到显着改善。对骨参数（例如小梁结构和皮质宽度）的组织形态学评估支持 3D 图像的观察。骨体积、小梁数量和小梁厚度增加，同时小梁间距减小。对未移植小鼠或移植了来自 oim 小鼠的 BM 细胞的小鼠的分析显示，骨参数持续恶化。移植的小鼠体重增加，自发性骨折的可能性降低，而对照小鼠的临床症状恶化，最终出现驼背。这些发现有力地支持了造血干细胞产生骨细胞的概念。此外，它们与临床移植研究的观察结果一致，并表明造血干细胞在成骨不全症中的治疗潜力。
To test the hypothesis that hematopoietic stem cells (HSCs) generate bone cells using bone marrow (BM) cell transplantation in a mouse model of osteogenesis imperfecta (OI). OI is a genetic disorder resulting from abnormal amount and/or structure of Type I collagen and is characterized by osteopenia, fragile bones and skeletal deformities. Homozygous OI murine mice (oim; B6C3Fe a/a-Col1a2oim/J) offer excellent recipients for transplantation of normal HSCs, because fast turnover of osteoprogenitors has been shown. We transplanted BM mononuclear cells or 50 BM cells highly enriched for HSCs from transgenic enhanced green fluorescent protein (EGFP) mice into irradiated oim mice and analyzed changes in bone parameters using longitudinal Micro-Computed Tomography (micro-CT). Dramatic improvements were observed in 3D micro-CT images of these bones 3 to 6 months post-transplantation when the mice showed high levels of hematopoietic engraftment. Histomorphometric assessment of the bone parameters such as trabecular structure and cortical width supported observations from 3D images. There was an increase in bone volume, trabecular number and trabecular thickness with a concomitant decrease in trabecular spacing. Analysis of a non-engrafted mouse or a mouse that was transplanted with BM cells from oim mice showed continued deterioration in the bone parameters. The engrafted mice gained weight and became less prone to spontaneous fractures while the control mice worsened clinically and eventually developed kyphosis. These findings strongly support the concept that HSCs generate bone cells. Furthermore, they are consistent with observations from clinical transplantation studies and suggest therapeutic potentials of HSCs in OI.
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