Microencapsulated rabbit adipose stem cells initiate tissue regeneration in a rabbit ear defect model
Microencapsulated rabbit adipose stem cells initiate tissue regeneration in a rabbit ear defect model
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DOI：
10.1002/term.2702
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发表时间：
2018-07-01
影响因子：
3.3
通讯作者：
Boyan, Barbara D.
中科院分区：
文献类型：
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作者：
Leslie, Shirae K.;Cohen, David J.;Boyan, Barbara D.
基于细胞的组织工程可以促进软骨组织再生，但分娩后细胞保留在植入部位是有问题的。含有用软骨形成介质预处理的脂肪干细胞（ASC）的藻酸盐微珠已成功用于再生大鼠剑突关键尺寸缺损的透明软骨，这表明它们可用于治疗耳朵等弹性软骨的缺损。为了测试这一点，我们使用了由低粘度、高甘露糖醛酸医用级藻酸盐制成的微珠，使用高静电势和含有葡萄糖的钙交联溶液。将含有兔 ASC (rbASC) 的微珠两侧植入六只骨骼成熟的雄性新西兰白兔的 3 毫米临界尺寸软骨中耳缺损处（空缺损；不含细胞的微珠；含有细胞的微珠；含有细胞的可降解微珠；以及自体移植物）。植入后十二周，通过 microCT 和组织学评估再生情况。在软骨形成培养基中培养的微囊 rbASC 表达聚集蛋白聚糖、II 型胶原蛋白和 X 型胶原蛋白的 mRNA。组织学上，空缺处含有纤维组织；缺损处仍存在不含细胞的微珠，并被纤维组织包围；带有 rbASC 的不可降解珠子启动软骨再生； microCT 也证实了含有细胞的可降解微珠产生了未成熟的骨样组织；自体移植物表现为正常的耳廓软骨，但未与缺损周围的组织完全融合。弹性蛋白是耳软骨的标志，但在新软骨中并不明显。这种输送系统提供了耳软骨再生的潜力，但必须考虑治疗部位的血管分布和诱导弹性蛋白的因素的使用。
Cell-based tissue engineering can promote cartilage tissue regeneration, but cell retention in the implant site post-delivery is problematic. Alginate microbeads containing adipose stem cells (ASCs) pretreated with chondrogenic media have been used successfully to regenerate hyaline cartilage in critical size defects in rat xiphoid suggesting that they may be used to treat defects in elastic cartilages such as the ear. To test this, we used microbeads made with low viscosity, high mannuronate medical grade alginate using a high electrostatic potential, and a calcium cross linking solution containing glucose. Microbeads containing rabbit ASCs (rbASCs) were implanted bilaterally in 3mm critical size midcartilage ear defects of six skeletally mature male New Zealand White rabbits (empty defect; microbeads without cells; microbeads with cells; degradable microbeads with cells; and autograft). Twelve weeks post-implantation, regeneration was assessed by microCT and histology. Microencapsulated rbASCs cultured in chondrogenic media expressed mRNAs for aggrecan, Type II collagen, and Type X collagen. Histologically, empty defects contained fibrous tissue; microbeads without cells were still present in defects and were surrounded by fibrous tissue; nondegradable beads with rbASCs initiated cartilage regeneration; degradable microbeads with cells produced immature bone-like tissue, also demonstrated by microCT; and autografts appeared as normal auricular cartilage but were not fully integrated with the tissue surrounding the defect. Elastin, the hallmark of auricular cartilage, was not evident in the neocartilage. This delivery system offers the potential for regeneration of auricular cartilage, but vascularity of the treatment site and use of factors that induce elastin must be considered.