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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Main Authors: Carla Cunha, Catarina Leite Pereira, Joana R. Ferreira, Cláudia Ribeiro-Machado, Sibylle Grad, Susana G. Santos, Raquel M. Gonçalves
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/17/9609
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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.
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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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