Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside
| Autor: | Bach, Frances C, Tellegen, Anna R, Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A M, de Vries, Stefan A H, Creemers, Laura B, Benz, Karin, Meij, Björn P, Ito, Keita, Tryfonidou, Marianna A, Orthopedie en neurochirurgie, dCSCA RMSC-1, LS Equine Muscoskeletal Biology, Onderzoek, dCSCA AVR, LS Algemene chirurgie, Diagnostische beeldvorming |
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| Přispěvatelé: | Orthopedie en neurochirurgie, dCSCA RMSC-1, LS Equine Muscoskeletal Biology, Onderzoek, dCSCA AVR, LS Algemene chirurgie, Diagnostische beeldvorming, Orthopaedic Biomechanics |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty regenerative medicine canine Matrix (biology) SDG 3 – Goede gezondheid en welzijn Regenerative medicine Canine Extracellular matrix 03 medical and health sciences SDG 3 - Good Health and Well-being Notochordal cells medicine human Bone regeneration Demineralized bone matrix business.industry Mesenchymal stem cell Intervertebral disc Chondrogenesis notochordal cells 030104 developmental biology medicine.anatomical_structure Oncology intervertebral disc business Research Paper Human |
| Zdroj: | Oncotarget, 9(41), 26507. Impact Journals Oncotarget, 9(41), 26507-26526. Impact Journals Oncotarget Oncotarget, 9(41), 26507. Impact Journals LLC |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.25476 |
| Popis: | The socioeconomic burden of chronic back pain related to intervertebral disc (IVD) disease is high and current treatments are only symptomatic. Minimally invasive strategies that promote biological IVD repair should address this unmet need. Notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) during IVD maturation and degeneration. The regenerative potential of NC-secreted substances on CLCs and mesenchymal stromal cells (MSCs) has already been demonstrated. However, identification of these substances remains elusive. Innovatively, this study exploits the regenerative NC potential by using healthy porcine NC-derived matrix (NCM) and employs the dog as a clinically relevant translational model. NCM increased the glycosaminoglycan and DNA content of human and canine CLC aggregates and facilitated chondrogenic differentiation of canine MSCs in vitro. Based on these results, NCM, MSCs and NCM+MSCs were injected in mildly (spontaneously) and moderately (induced) degenerated canine IVDs in vivo and, after six months of treatment, were analyzed. NCM injected in moderately (induced) degenerated canine IVDs exerted beneficial effects at the macroscopic and MRI level, induced collagen type II-rich extracellular matrix production, improved the disc height, and ameliorated local inflammation. MSCs exerted no (additive) effects. In conclusion, NCM induced in vivo regenerative effects on degenerated canine IVDs. NCM may, comparable to demineralized bone matrix in bone regeneration, serve as 'instructive matrix', by locally releasing growth factors and facilitating tissue repair. Therefore, intradiscal NCM injection could be a promising regenerative treatment for IVD disease, circumventing the cumbersome identification of bioactive NC-secreted substances. |
| Databáze: | OpenAIRE |
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