Intra-articular Injected Synovial Stem Cells Differentiate into Meniscal Cells Directly and Promote Meniscal Regeneration Without Mobilization to Distant Organs in Rat Massive Meniscal Defect
Intra-articular Injected Synovial Stem Cells Differentiate into Meniscal Cells Directly and Promote Meniscal Regeneration Without Mobilization to Distant Organs in Rat Massive Meniscal Defect
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DOI：
10.1634/stemcells.2008-0616
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发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Kobayashi, Eiji
中科院分区：
文献类型：
--
作者：
Horie, Masafumi;Sekiya, Ichiro;Kobayashi, Eiji
膝关节骨关节炎，这可能是由骨骼缺陷引起的，构成了一个越来越常见的医疗问题。由于膝关节内软骨前体缺乏细胞动力学，大面积骨缺损的修复仍然是一个挑战。滑膜在骨愈合的自然过程中起着关键作用，并含有具有高软骨形成潜力的间充质干细胞（MSC）。在这里，我们研究了关节内注射滑膜间充质干细胞是否能增强大鼠巨大骨缺损的骨再生。为了追踪注射的细胞，我们开发了表达双荧光素酶（Luc）和LacZ的转基因大鼠。从大鼠滑膜来源的细胞表现出集落形成能力和多向分化潜能，这两个特征的MSC。系统聚类分析显示，滑膜细胞基因表达与滑膜间充质干细胞基因表达的关系较骨髓间充质干细胞更接近。将500万份Luc/LacZ +滑膜-MSCs注射到野生型大鼠的大面积滑膜切除的膝关节内后2 ~ 8周，肉眼可见滑膜再生明显好于对照组。12周后，再生组织LacZ染色阳性，有2型胶原生成，透射电镜下可见明显的软骨样改变。在体内发光分析中，在3天的时间内，在切除膝关节的半月板中光子增加，然后在所有其他器官中未检测到光子减少。Real-time PCR检测结果显示，除滑膜外，其他组织中均未检测到LacZ基因的表达。滑膜间充质干细胞注射到大面积切除的膝关节中，粘附在病变处，直接分化为软骨细胞，促进软骨再生，而不动员到远处器官。干细胞2009;27：878-887
Osteoarthritis in the knees, which can be caused by meniscal defect, constitutes an increasingly common medical problem. Repair for massive meniscal defect remains a challenge owing to a lack of cell kinetics for the menisci precursors in knee joint. The synovium plays pivotal roles during the natural course of meniscal healing and contains mesenchymal stem cells (MSCs) with high chondrogenic potential. Here, we investigated whether intra-articular injected synovium-MSCs enhanced meniscal regeneration in rat massive meniscal defect. To track the injected cells, we developed transgenic rats expressing dual luciferase (Luc) and LacZ. The cells derived from synovium of the rats demonstrated colony-forming ability and multipotentiality, both characteristics of MSCs. Hierarchical clustering analysis revealed that gene expression of meniscal cells was closer to that of synovium-MSCs than to that of bone marrow-MSCs. Two to 8 weeks after five million Luc/LacZ + synovium-MSCs were injected into massive meniscectomized knee of wild-type rat, macroscopically, the menisci regenerated much better than it did in the control group. After 12 weeks, the regenerated menisci were LacZ positive, produced type 2 collagen, and showed meniscal features by transmission electron microscopy. In in-vivo luminescence analysis, photons increased in the meniscus-resected knee over a 3-day period, then decreased without detection in all other organs. LacZ gene derived from MSCs could not be detected in other organs except in synovium by real-time PCR. Synovium-MSCs injected into the massive meniscectomized knee adhered to the lesion, differentiated into meniscal cells directly, and promoted meniscal regeneration without mobilization to distant organs. STEM CELLS 2009;27:878-887