Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells
Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells
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DOI：
10.1002/jor.1100160202
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发表时间：
1998-03-01
影响因子：
2.8
通讯作者：
Kadiyala, S
中科院分区：
文献类型：
--
作者：
Bruder, SP;Kurth, AA;Kadiyala, S
骨髓含有一群罕见的祖细胞，能够分化成骨、软骨、肌腱和其他结缔组织。这些细胞，被称为间充质干细胞，可以从动物和人类中纯化和培养扩增，并且已经显示出当递送到实验动物的肌肉骨骼缺陷部位时再生功能组织。为了测试纯化的人间充质干细胞治愈临床上显著的骨缺损的能力，将从正常人骨髓分离的间充质干细胞培养扩增，加载到陶瓷载体上，并植入成年无胸腺大鼠股骨中的临界尺寸节段缺损中。为了比较，无细胞陶瓷植入对侧肢体。在第4、8或12周时对动物实施安乐死，并通过高分辨率X线摄影、免疫组织化学、定量组织形态学和生物力学测试对愈合的骨缺损进行比较。在加载间充质干细胞的样品中，到8周时新骨的放射学和组织学证据是明显的，并且组织形态计量学证明到12周时骨形成增加。生物力学评价证实，植入间充质干细胞陶瓷的股骨明显强于接受无细胞陶瓷的股骨。这些研究表明，人类间充质干细胞可以在临床上显著的骨缺损中再生骨，因此可能提供自体骨移植的替代方案。
Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, tendon, and other connective tissues. These cells, referred to as mesenchymal stem cells, can be purified and culture-expanded from animals and humans and have been shown to regenerate functional tissue when delivered to the site of musculoskeletal defects in experimental animals. To test the ability of purified human mesenchymal stem cells to heal a clinically significant bone defect, mesenchymal stem cells isolated from normal human bone marrow were culture-expanded, loaded onto a ceramic carrier, and implanted into critical-sized segmental defects in the femurs of adult athymic rats. For comparison, cell-free ceramics were implanted in the contralateral limb. The animals were euthanized at 4, 8, or 12 weeks, and healing bone defects were compared by high-resolution radiography, immunohistochemistry, quantitative histomorphometry, and biomechanical testing. In mesenchymal stem cell-loaded samples, radiographic and histologic evidence of new bone was apparent by 8 weeks and histomorphometry demonstrated increasing bone formation through 12 weeks. Biomechanical evaluation confirmed that femurs implanted with mesenchymal stem cell-loaded ceramics were significantly stronger than those that received cell-free ceramics. These studies demonstrate that human mesenchymal stem cells can regenerate bone in a clinically significant osseous defect and may therefore provide an alternative to autogenous bone grafts.