Regeneration of human-ear-shaped cartilage by co-culturing human microtia chondrocytes with BMSCs
Regeneration of human-ear-shaped cartilage by co-culturing human microtia chondrocytes with BMSCs
复制标题
人小耳软骨细胞与骨髓间充质干细胞共培养人耳形软骨再生
DOI：
10.1016/j.biomaterials.2014.02.043
复制
发表时间：
2014-06-01
期刊：
影响因子：
14
通讯作者：
Zhou, Guangdong
中科院分区：
文献类型：
--
作者：
Zhang, Lu;He, Aijuan;Zhou, Guangdong
在此之前，我们已经解决了体外工程化人耳形软骨的形状控制/维持的问题。因此，缺乏适用的细胞来源已成为阻碍该技术临床转化的主要问题。自体小耳软骨细胞（MCs）和骨髓基质细胞（BMSCs）都是有前途的软骨细胞，不涉及明显的供区发病率。然而，MCs的有限细胞可用性和软骨诱导的BMSCs在皮下环境中的异位成骨极大地限制了其在外耳重建中的应用。目前的研究表明，MCs具有很强的增殖能力，但伴随着软骨形成能力在传代过程中迅速丧失，表明使用扩增的MCs工程化整个耳朵的可行性差。幸运的是，MCs和BMSCs的共移植结果（25%MCs和75%BMSCs）表明MCs具有很强的软骨诱导能力，可促进BMSCs在皮下环境中稳定异位成软骨。此外，细胞标记表明，BMSCs可以转化为软骨细胞样细胞的共同培养的MC提供的软骨分化龛。最重要的是，通过将混合细胞（MCs和BMSCs）接种到预成型的可生物降解耳支架中，然后在裸鼠皮下植入12周，成功地构建了结构精致且具有适当弹性的人耳状软骨组织。这些结果可能提供一个有前途的策略，构建稳定的异位软骨与MC和干细胞（BMSCs）的自体外耳再造。(c)2014爱思唯尔有限公司版权所有。
Previously, we had addressed the issues of shape control/maintenance of in vitro engineered human-earshaped cartilage. Thus, lack of applicable cell source had become a major concern that blocks clinical translation of this technology. Autologous microtia chondrocytes (MCs) and bone marrow stromal cells (BMSCs) were both promising chondrogenic cells that did not involve obvious donor site morbidity. However, limited cell availability of MCs and ectopic ossification of chondrogenically induced BMSCs in subcutaneous environment greatly restricted their applications in external ear reconstruction. The current study demonstrated that MCs possessed strong proliferation ability but accompanied with rapid loss of chondrogenic ability during passage, indicating a poor feasibility to engineer the entire ear using expanded MCs. Fortunately, the co-transplantation results of MCs and BMSCs (25% MCs and 75% BMSCs) demonstrated a strong chondroinductive ability of MCs to promote stable ectopic chondrogenesis of BMSCs in subcutaneous environment. Moreover, cell labeling demonstrated that BMSCs could transform into chondrocyte-like cells under the chondrogenic niche provided by co-cultured MCs. Most importantly, a human-ear-shaped cartilaginous tissue with delicate structure and proper elasticity was successfully constructed by seeding the mixed cells (MCs and BMSCs) into the pre-shaped biodegradable ear-scaffold followed by 12 weeks of subcutaneous implantation in nude mouse. These results may provide a promising strategy to construct stable ectopic cartilage with MCs and stem cells (BMSCs) for autologous external ear reconstruction. (c) 2014 Elsevier Ltd. All rights reserved.