Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration
Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration
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DOI：
10.1634/stemcells.2006-0281
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发表时间：
2007-03-01
期刊：
影响因子：
5.2
通讯作者：
Sekiya, Ichiro
中科院分区：
文献类型：
--
作者：
Koga, Hideyuki;Muneta, Takeshi;Sekiya, Ichiro
我们以前证明，滑膜来源的骨髓间充质干细胞有更大的体外软骨形成能力比其他间充质组织，表明软骨再生的上级细胞来源。在这里，我们将未分化的滑膜来源的MSC移植到成年兔的全层关节软骨缺损中，并定义了细胞事件，以阐明MSC多向分化的机制。在膝关节中创建全层骨软骨缺损;缺损用1，1 '-双十八烷基-3，3，3'，3 '-四甲基吲哚羰花青高氯酸盐标记的MSC填充，并用骨膜覆盖。4周后，虽然细胞密度下降，但移植的MSCs广泛产生大量的软骨基质。骨膜变薄，骨膜中的软骨祖细胞产生少量软骨基质。在更深的区域，移植的MSC进展为肥大的软骨细胞样细胞。在深层，一些移植细胞分化为骨细胞，随后被宿主细胞取代。在下一阶段，骨和软骨之间的边界向上移动。此外，天然软骨和再生组织之间的整合得到改善。至少在24周后，移植的MSC来源的软骨细胞样细胞仍然存在。MSC组的组织学评分持续改善，并且始终优于其他两个对照组。免疫组织化学分析和透射电镜证实，骨髓间充质干细胞产生丰富的软骨基质。我们证明了移植的滑膜来源的MSC随着时间的推移根据微环境而改变。我们的研究结果将推进基于MSC的软骨损伤治疗策略，并为MSC的多向分化机制提供线索。
We previously demonstrated that synovium-derived MSCs had greater in vitro chondrogenic ability than other mesenchymal tissues, suggesting a superior cell source for cartilage regeneration. Here, we transplanted undifferentiated synovium-derived MSCs into a full-thickness articular cartilage defect of adult rabbits and defined the cellular events to elucidate the mechanisms that govern multilineage differentiation of MSCs. Full-thickness osteochondral defects were created in the knee; the defects were filled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled MSCs and covered with periosteum. After 4 weeks, although the cell density decreased, transplanted MSCs produced a great amount of cartilage matrix extensively. The periosteum became thinner, and chondroprogenitors in the periosteum produced a small amount of cartilage matrix. In the deeper zone, transplanted MSCs progressed to the hypertrophic chondrocyte-like cells. In the deep zone, some transplanted cells differentiated into bone cells and were replaced with host cells thereafter. In the next phase, the border between bone and cartilage moved upwards. In addition, integrations between native cartilage and regenerated tissue were improved. Chondrocyte-like cells derived from the transplanted MSCs still remained at least after 24 weeks. Histological scores of the MSC group improved continuously and were always better than those of two other control groups. Immunohistological analyses and transmission electron microscopy confirmed that the MSCs produced abundant cartilage matrix. We demonstrated that transplanted synovium-derived MSCs were altered over a time course according to the microenvironments. Our results will advance MSC-based therapeutic strategies for cartilage injury and provide the clues for the mechanisms that govern multilineage differentiation of MSCs.