Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair.
Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair.
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DOI：
10.1155/2017/1960965
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发表时间：
2017
影响因子：
4.3
通讯作者：
Norimasa N
中科院分区：
文献类型：
--
作者：
Chijimatsu R;Ikeya M;Yasui Y;Ikeda Y;Ebina K;Moriguchi Y;Shimomura K;Hart DA;Hideki Y;Norimasa N
间充质干细胞（Mesenchymal stem cells，MSC）来源于诱导性多能干细胞（induced pluripotent stem cells，iPSCs），是一种有前途的骨骼疾病修复的细胞来源。最近，神经嵴细胞（NCCs）被报道是有效的诱导间充质祖细胞，有潜力分化成骨软骨细胞谱系。我们的目的是研究来源于iPSCs的MSC样细胞通过NCCs用于骨软骨修复的可行性。最初，在体外产生并表征源自iPSC-NCC（iNCC）的MSC样细胞。这些iNCC衍生的MSC样细胞（iNCMSC）表现出同质群体和骨软骨分化的潜力。在培养过程中未检测到多能标志物的上调。第二，我们将iNCMSC衍生的组织工程构建体植入大鼠骨软骨缺损中，而没有任何特定分化谱系的预诱导。植入的细胞在植入部位仍然存活，而它们未能修复缺陷，体内只有很少的骨软骨组织发育。关于肿瘤发生，植入的细胞逐渐消失，在整个2个月的随访中未检测到恶性细胞。虽然该研究未显示iNCMSC在未分化条件下植入时具有修复骨软骨缺损的功效，但iNCMSC在适当条件下在体外表现出良好的软骨形成潜力。通过进一步优化，iNCMSCs可能成为软骨组织工程的新来源。
Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage.