Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β.
Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β.
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DOI：
10.1186/s13287-017-0696-x
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发表时间：
2017-11-02
影响因子：
7.5
通讯作者：
Bhutani N
中科院分区：
文献类型：
--
作者：
Lee J;Smeriglio P;Chu CR;Bhutani N
诱导多能干细胞(IPSC)为再生医学提供了无限的患者特异性细胞来源。成体细胞在软骨修复方面取得的成功有限，但幼年软骨细胞(来自13岁以下的捐赠者)已被确定为生成优质软骨。基于这一观点，这些研究的目的是将人类IPSC来源的软骨细胞(HiChondrocell)与成人和青少年软骨细胞进行比较，并确定控制其功能的共同分子因素。将软骨细胞的表型和功能特征与幼年和成年软骨细胞进行比较。利用全球基因表达谱分析、独立基因表达和功能丧失研究来测试对软骨细胞和幼年软骨细胞功能具有调节作用的分子因素。在此，我们报道了与成年软骨细胞相比，IPSC来源的软骨细胞在更快的细胞增殖速度和对IL-1β的抵抗力方面模仿了幼年软骨细胞。全基因组转录组分析显示，与成年软骨细胞相比，幼年和IPSC来源的软骨细胞中都富含独特的ECM因子和免疫反应途径。功能丧失研究表明，CD24是一种细胞表面受体，富含在幼年软骨细胞和软骨细胞中，在这些软骨细胞群体中，CD24是一种快速增殖和抵抗促炎信号的调节因子。我们的研究发现，软骨细胞模仿幼年软骨细胞具有双重优势，即更快的增殖和对炎性细胞因子IL-1β的较低反应。虽然IPSC来源的细胞发育不成熟对肌肉和脑等组织可能是一个挑战，但我们的研究表明，对于成年后再生能力有限的软骨等组织来说，这是有利的。本文的在线版本(doi：10.1186/s13287-0170696-x)包含补充材料，授权用户可以使用。
Induced pluripotent stem cells (iPSC) provide an unlimited patient-specific cell source for regenerative medicine. Adult cells have had limited success in cartilage repair, but juvenile chondrocytes (from donors younger than 13 years of age) have been identified to generate superior cartilage. With this perspective, the aim of these studies was to compare the human iPSC-derived chondrocytes (hiChondrocytes) to adult and juvenile chondrocytes and identify common molecular factors that govern their function. Phenotypic and functional characteristics of hiChondrocytes were compared to juvenile and adult chondrocytes. Analyses of global gene expression profiling, independent gene expression, and loss-of-function studies were utilized to test molecular factors having a regulatory effect on hiChondrocytes and juvenile chondrocyte function. Here, we report that the iPSC-derived chondrocytes mimic juvenile chondrocytes in faster cell proliferation and resistance to IL-1β compared to adult chondrocytes. Whole genome transcriptome analyses revealed unique ECM factors and immune response pathways to be enriched in both juvenile and iPSC-derived chondrocytes as compared to adult chondrocytes. Loss-of-function studies demonstrated that CD24, a cell surface receptor enriched in both juvenile chondrocytes and hiChondrocytes, is a regulatory factor in both faster proliferation and resistance to proinflammatory cues in these chondrocyte populations. Our studies identify that hiChondrocytes mimic juvenile chondrocytes for the dual advantage of faster proliferation and a reduced response to the inflammatory cytokine IL-1β. While developmental immaturity of iPSC-derived cells can be a challenge for tissues like muscle and brain, our studies demonstrate that it is advantageous for a tissue like cartilage that has limited regenerative ability in adulthood. The online version of this article (doi:10.1186/s13287-017-0696-x) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
14
作者：
Strehin, Iossif;Nahas, Zayna;Arora, Karun;Nguyen, Thao;Elisseeff, Jennifer
通讯作者：
Elisseeff, Jennifer
影响因子：
64.5
作者：
Dolmetsch R;Geschwind DH
通讯作者：
Geschwind DH
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
DOI：
10.1126/science.1168988
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen GY;Tang J;Zheng P;Liu Y
通讯作者：
Liu Y