Generation of Functional Mesenchymal Stem Cells from Different Induced Pluripotent Stem Cell Lines
Generation of Functional Mesenchymal Stem Cells from Different Induced Pluripotent Stem Cell Lines
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DOI：
10.1089/scd.2013.0111
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发表时间：
2014-05-15
影响因子：
4
通讯作者：
Bartold, P. Mark
中科院分区：
文献类型：
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作者：
Hynes, Kim;Menicanin, Danijela;Bartold, P. Mark
间充质干细胞（MSC）的治疗潜力突出了鉴定这些细胞易于获取和可靠来源的必要性。获得大量间充质干细胞的另一种来源是通过诱导多能干细胞（iPSC）的受控分化。在本研究中，iPSC菌落在MSC培养基中培养2周。然后选择连续传代快速生长的msc样细胞，具有典型的成纤维细胞形态，并且能够在没有饲养细胞的标准培养瓶上增殖。从三种不同的体细胞组织：牙龈、牙周韧带（PDL）和肺中培养出间质干细胞样细胞。iPSC-MSC样细胞表达关键的msc相关标志物（CD73、CD90、CD105、CD146和CD166），缺乏多能标志物（TRA160、TRA181和碱性磷酸酶）和造血标志物（CD14、CD34和CD45）的表达。体外ipsc - mscs样细胞显示分化成成骨细胞、脂肪细胞和软骨细胞的能力。将ipsc - msc样细胞皮下植入NOD/SCID小鼠体内，结果表明，只有pdl来源的ipsc - msc样细胞具有形成成熟矿化结构的能力，这些结构在组织学上与成熟骨相似。这些发现表明，控制诱导iPSC诱导成纤维样细胞，其表型和功能与成人间充质干细胞相似，是获得易于获得的祖细胞来源的一种有吸引力的方法，可用于骨科和牙科相关的组织工程应用。然而，iPSC- msc样细胞的详细表征将是重要的，因为来自不同iPSC系的msc样细胞在其分化能力方面表现出可变性。
The therapeutic potential of mesenchymal stem cells (MSC) has highlighted the need for identifying easily accessible and reliable sources of these cells. An alternative source for obtaining large populations of MSC is through the controlled differentiation of induced pluripotent stem cells (iPSC). In the present study, colonies of iPSC were cultured in MSC culture media for 2 weeks. Serial passaging then selected for fast growing MSC-like cells with a typical fibroblastic morphology and the capacity to proliferate on standard culture flasks without feeder cells. MSC-like cells were developed from iPSC lines arising from three different somatic tissues: gingiva, periodontal ligament (PDL), and lung. The iPSC-MSC like cells expressed key MSC-associated markers (CD73, CD90, CD105, CD146, and CD166) and lacked expression of pluripotent markers (TRA160, TRA181, and alkaline phosphatase) and hematopoietic markers (CD14, CD34, and CD45). In vitro iPSC-MSC-like cells displayed the capacity to differentiate into osteoblasts, adipocytes, and chondrocytes. In vivo subcutaneous implantation of the iPSC-MSC-like cells into NOD/SCID mice demonstrated that only the PDL-derived iPSC-MSC-like cells exhibited the capacity to form mature mineralized structures which were histologically similar to mature bone. These findings demonstrate that controlled induction of iPSC into fibroblastic-like cells that phenotypically and functionally resemble adult MSC is an attractive approach to obtain a readily available source of progenitor cells for orthopedic and dental-related tissue-engineering applications. However, a detailed characterization of the iPSC-MSC-like cells will be important, as MSC-like cells derived from different iPSC lines exhibit variability in their differentiation capacity.