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The species-specific regenerative effects of notochordal cell-conditioned medium on chondrocyte-like cells derived from degenerated human intervertebral discs

机译:脊索细胞条件培养基对变性人椎间盘衍生的软骨细胞样细胞的种特异性再生作用

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During intervertebral disc (IVD) maturation, the main cell type shifts from notochordal cells (NCs) to chondrocyte-like cells (CLCs). NCs secrete factors with regenerative potential, making them an interesting focus for regenerative treatments. During initial development, these strategies preferably employ non-human donors due to easy availability of their NC-rich nucleus pulposus (NP) tissue. To increase the success of translating these strategies for clinical application, this study aimed to delineate whether NC-secreted factors of different species have a regenerative effect on human CLCs. Human, canine and porcine NC-rich NP tissue and NC-conditioned medium (NCCM) were analysed biochemically and histologically. Human CLC micro-aggregates from degenerated IVDs were cultured in human, canine or porcine NCCM. Collagen, glycosaminoglycan (GAG) and DNA content was determined and histology was performed. Canine and porcine NPs were richer in NCs than human NPs. Human NPs contained the highest collagen content, whereas the DNA and GAG content of canine NPs was significantly higher than that of human or porcine NPs. NCCM from all species significantly increased the DNA and GAG content of the human CLC micro-aggregates. Porcine and canine NCCM were significantly more potent than human NCCM in inducing GAG deposition, whereas only human NCCM induced collagen type II production. Secreted factors from human, canine and porcine NC-rich NPs exerted regenerative effects on human CLCs, indicating a cross-species effect. Bioactive compound(s) are present in NCCM of different species that may reverse human IVD degeneration, supporting further research into strategies based on NC-technology employing canine or porcine models for their translation into humans.
机译:在椎间盘(IVD)成熟期间,主要细胞类型从脊索细胞(NCs)转变为软骨样细胞(CLCs)。 NCs分泌具有再生潜能的因子,使它们成为再生治疗的有趣焦点。在最初的开发过程中,由于容易获得富含NC的髓核(NP)组织,因此这些策略最好使用非人类供体。为了提高翻译这些策略用于临床的成功率,本研究旨在描述不同物种的NC分泌因子是否对人CLC具有再生作用。对人,犬和猪的富含NC的NP组织和NC条件培养基(NCCM)进行了生化和组织学分析。在人,犬或猪NCCM中培养来自退化IVD的人CLC微聚集体。确定胶原蛋白,糖胺聚糖(GAG)和DNA含量并进行组织学检查。犬和​​猪的NP比人NP富含NC。人NP包含最高的胶原蛋白含量,而犬NP的DNA和GAG含量显着高于人或猪NP。来自所有物种的NCCM显着增加了人类CLC微聚集体的DNA和GAG含量。猪和犬NCCM在诱导GAG沉积方面比人NCCM显着更有效,而只有人NCCM诱导II型胶原产生。来自人,犬和猪的富含NC的NP的分泌因子对人CLC产生了再生作用,表明具有种间效应。具有生物活性的化合物存在于不同物种的NCCM中,它们可能会逆转人类IVD变性,从而支持对基于NC技术的策略的进一步研究,该策略采用犬或猪模型将其翻译为人类。

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