Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma

Wei Hong Chen, Hen Yu Liu, Wen Cheng Lo, Shinn Chih Wu, Chau Hwa Chi, Hsueh Yuan Chang, Shih Hsiang Hsiao, Chih Hsiung Wu, Wen Ta Chiu, Bao Ji Chen, Win Ping Deng

研究成果: 雜誌貢獻文章同行評審

99 引文 斯高帕斯(Scopus)

摘要

An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration.

原文英語
頁(從 - 到)5523-5533
頁數11
期刊Biomaterials
30
發行號29
DOIs
出版狀態已發佈 - 10月 2009

ASJC Scopus subject areas

  • 生物工程
  • 陶瓷和複合材料
  • 生物物理學
  • 生物材料
  • 材料力學

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