Suchergebnisse

Magnetic nanoparticles (MNPs) are attractive tools to overcome limitations of current regenerative medicine strategies, demonstrating potential to integrate therapeutic and diagnostic functionalities in highly controlled systems. In traditional tissue engineering (TE) approaches, the MNPs association with stem cells in a three-dimensional (3D) template offers the possibility to achieve a mechano-magnetic responsive system, enabling remote control actuation. Herein, we propose to study the role of MNPs integrated in κ-carrageenan (κC) hydrogels in the cellular response of human adipose-derived stem cells (hASCs) aiming at cartilage TE applications. The results indicated that the concentration of MNPs in the κC hydrogels influences cellular behavior, tuning a positive effect on cell viability, cell content and metabolic activity of hASCs, with the most promising outcomes found in 5% MNP-κC matrices. Although hASCs laden in MNPs-free- and MNPs-κC hydrogels showed similar metabolic and proliferation levels, MNPs κC hydrogels under magnetic actuation evidenced an instructive effect on hASCs, at a gene expression level, towards chondrogenic phenotype even in basic medium cultures. Therefore, the MNPs-based systems developed in this study may contribute to advanced strategies towards cartilage-like engineered substitutes. ; The authors wish to acknowledge the financial support of the Portuguese Foundation for Science and Technology for the PhD grant(SFRH/BD/64070/2009) and Post-Doc grant (SFRH/BPD/91072/2012). In addition, the research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n REGPOT-CT2012-316331-POLARIS and under the projects MIT/ECE/0047/2009 and RL3-TECT-NORTE-07-0124-FEDER-000020 co-financed by ON.2 (NSRF), through ...

Stem cell therapies hold potential to stimulate tendon regeneration and homeostasis, which is maintained in response to the native mechanical environment. Activins are members of the mechano-responsive TGF-β superfamily that participates in the regulation of several downstream biological processes. Mechanosensitive membrane receptors such as activin can be activated in different types of stem cells via magnetic nanoparticles (MNPs) through remote magnetic actuation resulting in cell differentiation. In this work, we target the Activin receptor type IIA (ActRIIA) in human adipose stem cells (hASCs), using anti-ActRIIA functionalized MNPs, externally activated through a oscillating magnetic bioreactor. Upon activation, the phosphorylation of Smad2/3 is induced allowing translocation of the complex to the nucleus, regulating tenogenic transcriptional responses. Our study demonstrates the potential remote activation of MNPs tagged hASCs to trigger the Activin receptor leading to tenogenic differentiation. These results may provide insights toward tendon regeneration therapies. ; The authors acknowledge the financial support from the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No 739572 - The Discoveries CTR. This article is also a result of 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). ...