Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment

Bibliographic Details
Main Author: Matos, A. M.
Publication Date: 2020
Other Authors: Gonçalves, A. I., Rodrigues, M. T., Miranda, M. S., Haj, A. E., Reis, R. L., Gomes, Manuela E.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: https://hdl.handle.net/1822/66365
Summary: Injuries affecting load bearing tendon tissues are a significant clinical burden and efficient treatments are still unmet. Tackling tendon regeneration, tissue engineering strategies aim to develop functional substitutes that recreate native tendon milieu. Tendon mimetic scaffolds capable of remote magnetic responsiveness and functionalized magnetic nanoparticles (MNPs) targeting cellular mechanosensitive receptors are potential instructive tools to mediate mechanotransduction in guiding tenogenic responses. In this work, we combine magnetically responsive scaffolds and targeted Activin A type II receptor in human adipose stem cells (hASCs), under alternating magnetic field (AMF), to synergistically facilitate external control over signal transduction. The combination of remote triggering TGF-β/Smad2/3 using MNPs tagged hASCs, through magnetically actuated scaffolds, stimulates overall expression of tendon related genes and the deposition of tendon related proteins, in comparison to non-stimulated conditions. Moreover, the phosphorylation of Smad2/3 proteins and their nuclear co-localization was also more evident. Overall, biophysical stimuli resulting from magnetic scaffolds and magnetically triggered cells under AMF stimulation modulate the mechanosensing response of hASCs towards tenogenesis, holding therapeutic promise.
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spelling Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitmentmagnetic scaffoldsMagnetic stimulationTenogenic differentiationTGF-β/Smad2/3 signaling pathwayTGF-beta/Smad2/3 signaling pathwayScience & TechnologyInjuries affecting load bearing tendon tissues are a significant clinical burden and efficient treatments are still unmet. Tackling tendon regeneration, tissue engineering strategies aim to develop functional substitutes that recreate native tendon milieu. Tendon mimetic scaffolds capable of remote magnetic responsiveness and functionalized magnetic nanoparticles (MNPs) targeting cellular mechanosensitive receptors are potential instructive tools to mediate mechanotransduction in guiding tenogenic responses. In this work, we combine magnetically responsive scaffolds and targeted Activin A type II receptor in human adipose stem cells (hASCs), under alternating magnetic field (AMF), to synergistically facilitate external control over signal transduction. The combination of remote triggering TGF-β/Smad2/3 using MNPs tagged hASCs, through magnetically actuated scaffolds, stimulates overall expression of tendon related genes and the deposition of tendon related proteins, in comparison to non-stimulated conditions. Moreover, the phosphorylation of Smad2/3 proteins and their nuclear co-localization was also more evident. Overall, biophysical stimuli resulting from magnetic scaffolds and magnetically triggered cells under AMF stimulation modulate the mechanosensing response of hASCs towards tenogenesis, holding therapeutic promise.Authors acknowledge the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marine-derived biomaterials and stem cells”, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and the FCT Project MagTT PTDC/CTM-CTM/29930/2017 (POCI-01-0145-FEDER-29930). Authors acknowledge the HORIZON 2020 for the Achilles Twinning Project No. 810850. Authors also thank the European Research Council COG MagTendon No. 772817 and the ADG DYNACEUTICS No. 789119. Prof. Bernardo Almeida from Physics Department, University of Minho, is also acknowledged for assisting in the magnetic system assembling. Authors also acknowledge the INL - International Iberian Nanotechnology Laboratory (Braga, Portugal) for the magnetization analysis.ElsevierUniversidade do MinhoMatos, A. M.Gonçalves, A. I.Rodrigues, M. T.Miranda, M. S.Haj, A. E.Reis, R. L.Gomes, Manuela E.2020-092020-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/66365engMatos A. M., Gonçalves A. I., Rodrigues M. T., Miranda M. S., Haj A. E., Reis R. L., Gomes M. E. Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment, Acta Biomaterialia, Vol. 113, pp. 488-500, doi:10.1016/j.actbio.2020.07.009, 20201742-706110.1016/j.actbio.2020.07.00932652226https://doi.org/10.1016/j.actbio.2020.07.009info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-04-12T04:30:27Zoai:repositorium.sdum.uminho.pt:1822/66365Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T15:17:11.526864Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
title Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
spellingShingle Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
Matos, A. M.
magnetic scaffolds
Magnetic stimulation
Tenogenic differentiation
TGF-β/Smad2/3 signaling pathway
TGF-beta/Smad2/3 signaling pathway
Science & Technology
title_short Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
title_full Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
title_fullStr Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
title_full_unstemmed Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
title_sort Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment
author Matos, A. M.
author_facet Matos, A. M.
Gonçalves, A. I.
Rodrigues, M. T.
Miranda, M. S.
Haj, A. E.
Reis, R. L.
Gomes, Manuela E.
author_role author
author2 Gonçalves, A. I.
Rodrigues, M. T.
Miranda, M. S.
Haj, A. E.
Reis, R. L.
Gomes, Manuela E.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Matos, A. M.
Gonçalves, A. I.
Rodrigues, M. T.
Miranda, M. S.
Haj, A. E.
Reis, R. L.
Gomes, Manuela E.
dc.subject.por.fl_str_mv magnetic scaffolds
Magnetic stimulation
Tenogenic differentiation
TGF-β/Smad2/3 signaling pathway
TGF-beta/Smad2/3 signaling pathway
Science & Technology
topic magnetic scaffolds
Magnetic stimulation
Tenogenic differentiation
TGF-β/Smad2/3 signaling pathway
TGF-beta/Smad2/3 signaling pathway
Science & Technology
description Injuries affecting load bearing tendon tissues are a significant clinical burden and efficient treatments are still unmet. Tackling tendon regeneration, tissue engineering strategies aim to develop functional substitutes that recreate native tendon milieu. Tendon mimetic scaffolds capable of remote magnetic responsiveness and functionalized magnetic nanoparticles (MNPs) targeting cellular mechanosensitive receptors are potential instructive tools to mediate mechanotransduction in guiding tenogenic responses. In this work, we combine magnetically responsive scaffolds and targeted Activin A type II receptor in human adipose stem cells (hASCs), under alternating magnetic field (AMF), to synergistically facilitate external control over signal transduction. The combination of remote triggering TGF-β/Smad2/3 using MNPs tagged hASCs, through magnetically actuated scaffolds, stimulates overall expression of tendon related genes and the deposition of tendon related proteins, in comparison to non-stimulated conditions. Moreover, the phosphorylation of Smad2/3 proteins and their nuclear co-localization was also more evident. Overall, biophysical stimuli resulting from magnetic scaffolds and magnetically triggered cells under AMF stimulation modulate the mechanosensing response of hASCs towards tenogenesis, holding therapeutic promise.
publishDate 2020
dc.date.none.fl_str_mv 2020-09
2020-09-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/1822/66365
url https://hdl.handle.net/1822/66365
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Matos A. M., Gonçalves A. I., Rodrigues M. T., Miranda M. S., Haj A. E., Reis R. L., Gomes M. E. Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment, Acta Biomaterialia, Vol. 113, pp. 488-500, doi:10.1016/j.actbio.2020.07.009, 2020
1742-7061
10.1016/j.actbio.2020.07.009
32652226
https://doi.org/10.1016/j.actbio.2020.07.009
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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