Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration

作者: Giovanni Marfia , Rolando Campanella , Stefania Elena Navone , Ileana Zucca , Alessandro Scotti

DOI: 10.1186/S13075-014-0457-5

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摘要: Introduction: Biglycan is an important proteoglycan of the extracellular matrix intervertebral disc (IVD), and its decrease with aging has been correlated IVD degeneration. deficient (Bgn �/0 ) mice lack this protein undergo spontaneous degeneration aging, thus representing a valuable in vivo model for preliminary studies on therapies human progressive The purpose present study was to assess possible beneficial effects adipose-derived stromal cells (ADSCs) implants Bgn mouse model. Methods: To evaluate ADSC implant efficacy, were intradiscally (L1-L2) injected 8x10 4 ADSCs at 16 months old, when exhibit severe complete degeneration, evident both 7Tesla Magnetic Resonance Imaging (7TMRI) histology. Placebo treated assessed by 7TMRI analysis up 12 weeks post-transplantation. Mice then sacrificed implanted discs analyzed histology immunohistochemistry presence expression biglycan aggrecan area. Results: After treatment, revealed increase signal intensity within that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated survival occurred after implant. These acquired positive biglycan, specifically localized cells. Moreover, resulted significant tissue levels. Conclusion: Overall, work demonstrates into degenerated ameliorates damage, promotes new increased levels aggrecan. This suggests potential benefit chronic degenerative disease prompts further field.

参考文章(51)
B Johnstone, M Markopoulos, P Neame, B Caterson, Identification and characterization of glycanated and non-glycanated forms of biglycan and decorin in the human intervertebral disc. Biochemical Journal. ,vol. 292, pp. 661- 666 ,(1993) , 10.1042/BJ2920661
Hans Jörg Meisel, Vilma Siodla, Timothy Ganey, Yvonne Minkus, William C. Hutton, Olivera J. Alasevic, Clinical experience in cell-based therapeutics: Disc chondrocyte transplantation Biomolecular Engineering. ,vol. 24, pp. 5- 21 ,(2007) , 10.1016/J.BIOENG.2006.07.002
Dipika Gopal, Allen L. Ho, Amol Shah, John H. Chi, Molecular basis of intervertebral disc degeneration. Advances in Experimental Medicine and Biology. ,vol. 760, pp. 114- 133 ,(2012) , 10.1007/978-1-4614-4090-1_8
Joseph A. Buckwalter, Aging and degeneration of the human intervertebral disc. Spine. ,vol. 20, pp. 1307- 1314 ,(1995) , 10.1097/00007632-199506000-00022
Ritva I. Inkinen, Mikko J. Lammi, Kaija Puustjarvi, Eeva Kaapa, Sirpa Lehmonen, Markku I. Tammi, Relative increase of biglycan and decorin and altered chondroitin sulfate epitopes in the degenerating human intervertebral disc. The Journal of Rheumatology. ,vol. 25, pp. 506- 514 ,(1998)
Tianshun Xu, Paolo Bianco, Larry W. Fisher, Glenn Longenecker, Erica Smith, Steven Goldstein, Jeffrey Bonadio, Adele Boskey, Anne-Marie Heegaard, Beatrice Sommer, Kazuhito Satomura, Pedro Dominguez, Chengyan Zhao, Ashok B. Kulkarni, Pamela Gehron Robey, Marian F. Young, Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice Nature Genetics. ,vol. 20, pp. 78- 82 ,(1998) , 10.1038/1746
D Heinegård, T Larsson, Y Sommarin, A Franzén, M Paulsson, E Hedbom, Two novel matrix proteins isolated from articular cartilage show wide distributions among connective tissues. Journal of Biological Chemistry. ,vol. 261, pp. 13866- 13872 ,(1986) , 10.1016/S0021-9258(18)67101-7
Koichi Masuda, Yoichi Aota, Carol Muehleman, Yoshiyuki Imai, Masahiko Okuma, Eugene J. Thonar, Gunnar B. Andersson, Howard S. An, A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine. ,vol. 30, pp. 5- 14 ,(2005) , 10.1097/01.BRS.0000148152.04401.20
Jianfeng Xu, Deborah Meyers, Diha Freije, Sarah Isaacs, Kathy Wiley, Deborah Nusskern, Charles Ewing, Eric Wilkens, Piroska Bujnovszky, G. Steven Bova, Patrick Walsh, William Isaacs, Johanna Schleutker, Mika Matikainen, Teuvo Tammela, Tapio Visakorpi, Olli-P. Kallioniemi, Rebecca Berry, Daniel Schaid, Amy French, Shannon McDonnell, Jennifer Schroeder, Michael Blute, Stephen Thibodeau, Henrik Grönberg, Monika Emanuelsson, Jan-Erik Damber, Anders Bergh, Björn-Anders Jonsson, Jeffrey Smith, Joan Bailey-Wilson, John Carpten, Dietrich Stephan, Elizabeth Gillanders, Isaac Amundson, Tommi Kainu, Diana Freas-Lutz, Agnes Baffoe-Bonnie, Anne Van Aucken, Raman Sood, Francis Collins, Michael Brownstein, Jeffrey Trent, Evidence for a prostate cancer susceptibility locus on the X chromosome. Nature Genetics. ,vol. 20, pp. 175- 179 ,(1998) , 10.1038/2477
Howard S. An, Kenji Takegami, Hiroshi Kamada, Cahn M. Nguyen, Eugene J-M.A. Thonar, Kern Singh, Gunnar B. Andersson, Koichi Masuda, Intradiscal Administration of Osteogenic Protein-1 Increases Intervertebral Disc Height and Proteoglycan Content in the Nucleus Pulposus in Normal Adolescent Rabbits Spine. ,vol. 30, pp. 25- 32 ,(2005) , 10.1097/01.BRS.0000148002.68656.4D