Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs
Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or tr...
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MDPI AG
2021-09-01
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author | Carla Cunha Catarina Leite Pereira Joana R. Ferreira Cláudia Ribeiro-Machado Sibylle Grad Susana G. Santos Raquel M. Gonçalves |
author_facet | Carla Cunha Catarina Leite Pereira Joana R. Ferreira Cláudia Ribeiro-Machado Sibylle Grad Susana G. Santos Raquel M. Gonçalves |
author_sort | Carla Cunha |
collection | DOAJ |
description | Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation. |
first_indexed | 2024-03-10T08:10:09Z |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T08:10:09Z |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-d4a5a4c339494d7d82b05206eb79134c2023-11-22T10:46:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012217960910.3390/ijms22179609Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCsCarla Cunha0Catarina Leite Pereira1Joana R. Ferreira2Cláudia Ribeiro-Machado3Sibylle Grad4Susana G. Santos5Raquel M. Gonçalves6i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalAO Research Institute Davos, 7270 Davos, Switzerlandi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalIntervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.https://www.mdpi.com/1422-0067/22/17/9609intervertebral discMSCsrecruitmentbiomaterialsinflammation |
spellingShingle | Carla Cunha Catarina Leite Pereira Joana R. Ferreira Cláudia Ribeiro-Machado Sibylle Grad Susana G. Santos Raquel M. Gonçalves Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs International Journal of Molecular Sciences intervertebral disc MSCs recruitment biomaterials inflammation |
title | Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs |
title_full | Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs |
title_fullStr | Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs |
title_full_unstemmed | Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs |
title_short | Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs |
title_sort | therapeutic strategies for ivd regeneration through hyaluronan sdf 1 based hydrogel and intravenous administration of mscs |
topic | intervertebral disc MSCs recruitment biomaterials inflammation |
url | https://www.mdpi.com/1422-0067/22/17/9609 |
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