Osteogenesis of Heterotopically Transplanted Mesenchymal Stromal Cells in Rat Models of Chronic Kidney Disease
Osteogenesis of Heterotopically Transplanted Mesenchymal Stromal Cells in Rat Models of Chronic Kidney Disease
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DOI：
10.1002/jbmr.1994
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发表时间：
2013-12-01
影响因子：
6.2
通讯作者：
Schneider, Rebekka K.
中科院分区：
文献类型：
--
作者：
Kramann, Rafael;Kunter, Uta;Schneider, Rebekka K.
目前的研究是基于间充质基质细胞（MSC）的假设，有助于软组织钙化和异位成骨慢性肾脏病（CKD）。在健康对照动物和两种CKD和血管钙化大鼠模型中建立的基于胶原的三维模型中腹膜内移植大鼠MSC：（1）5/6肾切除+高磷饮食;和（2）腺嘌呤肾病。作为内部对照，将不含MSC的胶原凝胶移植到相同的动物中。在4周和8周后，MSC仍然是可检测的并且在胶原凝胶中增殖（荧光激活细胞分选[FACS]分析和荧光标记细胞后的共聚焦显微镜）。CKD动物的主动脉和含MSC的胶原凝胶在钙化方面表现出明显的相似性（显微计算机断层扫描[mu CT]，能量分散X射线[EDX]分析，钙含量），诱导成骨标志物，（即骨形态发生蛋白2 [BMP-2]、Runt相关转录因子2 [Runx 2]、碱性磷酸酶[ALP]），骨细胞标志物硬化蛋白的上调和细胞外基质重塑，骨桥蛋白、胶原蛋白I/III/IV、纤连蛋白和层粘连蛋白的表达增加。在健康对照动物和所有组的不含MSC的胶原凝胶中从未观察到钙化、骨生成和基质重塑。Paul Karl Horan 26（PKH-26）标记的3G 5阳性MSC在CKD动物中表达Runx 2和sclerostin，而PKH-26阴性迁移细胞不表达成骨标志物。总之，异位植入的MSC在CKD诱导的血管钙化的大鼠模型中进行成骨分化，支持我们的假设，即MSC可能参与CKD患者的异位钙化过程。(c)2013年美国骨与矿物质研究学会。
The current study is based on the hypothesis of mesenchymal stromal cells (MSCs) contributing to soft-tissue calcification and ectopic osteogenesis in chronic kidney disease (CKD). Rat MSCs were transplanted intraperitoneally in an established three-dimensional collagen-based model in healthy control animals and two rat models of CKD and vascular calcification: (1) 5/6 nephrectomy+high phosphorus diet; and (2) adenine nephropathy. As internal controls, collagen gels without MSCs were transplanted in the same animals. After 4 and 8 weeks, MSCs were still detectable and proliferating in the collagen gels (fluorescence-activated cell sorting [FACS] analysis and confocal microscopy after fluorescence labeling of the cells). Aortas and MSC-containing collagen gels in CKD animals showed distinct similarities in calcification (micro-computed tomography [mu CT], energy-dispersive X-ray [EDX] analysis, calcium content), induction of osteogenic markers, (ie, bone morphogenic protein 2 [BMP-2], Runt related transcription factor 2 [Runx2], alkaline phosphatase [ALP]), upregulation of the osteocytic marker sclerostin and extracellular matrix remodeling with increased expression of osteopontin, collagen I/III/IV, fibronectin, and laminin. Calcification, osteogenesis, and matrix remodeling were never observed in healthy control animals and non-MSC-containing collagen gels in all groups. Paul Karl Horan 26 (PKH-26)-labeled, 3G5-positive MSCs expressed Runx2 and sclerostin in CKD animals whereas PKH-26-negative migrated cells did not express osteogenic markers. In conclusion, heterotopically implanted MSCs undergo osteogenic differentiation in rat models of CKD-induced vascular calcification, supporting our hypothesis of MSCs as possible players in heterotopic calcification processes of CKD patients. (c) 2013 American Society for Bone and Mineral Research.