The dependence of in vivo stable ectopic chondrogenesis by human mesenchymal stem cells on chondrogenic differentiation in vitro
The dependence of in vivo stable ectopic chondrogenesis by human mesenchymal stem cells on chondrogenic differentiation in vitro
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人间充质干细胞体内稳定异位软骨形成对体外软骨分化的依赖性
DOI：
10.1016/j.biomaterials.2008.01.021
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发表时间：
2008-05-01
期刊：
影响因子：
14
通讯作者：
Cao, Yilin
中科院分区：
文献类型：
--
作者：
Liu, Kai;Zhou, Guang Dong;Cao, Yilin
体内微生态位通过定向分化在决定植入的间充质干细胞（MSCs）的命运中起着重要作用。不适当的体内生态位也可以改变外源性MSC的最终命运，即使它们在体内植入之前被体外诱导以表达特定的表型。研究表明，体外向软骨细胞分化的间充质干细胞在皮下环境中容易丧失表型，不能形成稳定的软骨。我们推测，诱导的MSC在皮下环境中不能维持表型是由于体外软骨分化不足，完全分化的MSC可以保持其软骨细胞样表型并形成稳定的异位软骨。为了验证这一假设，在植入前进行了延长的体外软骨诱导和软骨形成。将人骨髓干细胞（hBMSCs）接种于聚乳酸涂层的聚乙醇酸支架上。细胞-支架构建体进行软骨诱导4至12周，用于体外软骨形成，然后皮下植入裸鼠体内12或24周。通过大体观察、糖胺聚糖含量测定和组织学染色对植入前后的软骨进行评价。体外诱导8周后，组织学检查显示典型的软骨结构形成。然而，当体外诱导持续8周或更短时间时，部分结构在植入后变得骨化。相反，那些在体外诱导12周的细胞在体内植入后可以保持其软骨结构。这些结果表明，通过体外延长的软骨诱导达到的完全分化阶段是hBMSCs在体内形成稳定的异位软骨形成所必需的。(C)2008爱思唯尔有限公司版权所有。
In vivo niche plays an important role in determining the fate of implanted mesenchymal stem cells (MSCs) by directing committed differentiation. An inappropriate in vivo niche can also alter desired ultimate fate of exogenous MSCs even they are in vitro induced to express a specific phenotype before in vivo implantation. Studies have shown that in vitro chondrogenically differentiated MSCs are apt to lose their phenotype and fail to form stable cartilage in subcutaneous environment. We hypothesized that failure of maintaining the phenotype of induced MSCs in subcutaneous environment is due to the insufficient chondrogenic differentiation in vitro and fully differentiated MSCs can retain their chondrocyte-like phenotype and form stable ectopic cartilage. To test this hypothesis, extended in vitro chondrogenic induction and cartilage formation were carried out before implantation. Human bone marrow stem cells (hBMSCs) were seeded onto polylactic acid coated polyglycolic acid scaffolds. The cell-scaffold constructs were chondrogenically induced from 4 to 12 weeks for in vitro chondrogenesis, and then implanted subcutaneously into nude mice for 12 or 24 weeks. The engineered cartilages were evaluated by gross view, glycosaminoglycan content measurement, and histological staining before and after implantation. Histological examination showed typical cartilage structure formation after 8 weeks of induction in vitro. However, part of the constructs became ossified after implantation when in vitro induction lasted 8 weeks or less time. In contrast, those induced for 12 weeks in vitro could retain their cartilage structure after in vivo implantation. These results indicate that a fully differentiated stage achieved by extended chondrogenic induction in vitro is necessary for hBMSCs to form stable ectopic chondrogenesis in vivo. (C) 2008 Elsevier Ltd. All rights reserved.