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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Mesenchymal stem cell (MSC) transplantation has emerged as a promising approach for bone regeneration. Importantly, the beneficial effects of MSCs can be improved by modulating the expression levels of specific genes to stimulate MSC osteogenic differentiation. We have previously shown that Smurf1 silencing by using Locked Nucleic Acid-Antisense Oligonucleotides, in combination with a scaffold that sustainably releases low doses of BMP-2, was able to increase the osteogenic potential of MSCs in the presence of BMP-2 doses significantly smaller than those currently used in the clinic. This would potentially allow an important reduction in this protein in MSs-based treatments, and thus of the side effects linked to its administration. We have further improved this system by specifically targeting the Wnt pathway modulator Sfrp1. This approach not only increases MSC bone regeneration efficiency, but is also able to induce osteogenic differentiation in osteoporotic human MSCs, bypassing the need for BMP-2 induction, underscoring the regenerative potential of this system. Achieving successful osteogenesis with the sole use of LNA-ASOs, without the need of administering pro-osteogenic factors such as BMP-2, would not only reduce the cost of treatments, but would also open the possibility of targeting these LNA-ASOs specifically to MSCs in the bone marrow, allowing us to treat systemic bone loss such as that associated with osteoporosis.

Details

Title
Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing
Author
García-Sánchez, Daniel 1   VIAFID ORCID Logo  ; González-González, Alberto 1   VIAFID ORCID Logo  ; García-García, Patricia 2   VIAFID ORCID Logo  ; Reyes, Ricardo 3   VIAFID ORCID Logo  ; Pérez-Núñez, María Isabel 4 ; Riancho, José A 5   VIAFID ORCID Logo  ; Évora, Carmen 2   VIAFID ORCID Logo  ; Rodríguez-Rey, José Carlos 1 ; Pérez-Campo, Flor M 1   VIAFID ORCID Logo 

 Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVAL, 39012 Santander, Spain; [email protected] (D.G.-S.); [email protected] (A.G.-G.); [email protected] (J.C.R.-R.) 
 Department of Chemical Engineering and Pharmaceutical Technology, Institute of Biomedical Technologies (ITB), University of La Laguna, 38206 La Laguna, Spain; [email protected] (P.G.-G.); [email protected] (C.É.) 
 Department of Biochemistry, Microbiology, Cellular Biology and Genetics, Institute of Biomedical Technologies (ITB), University of La Laguna, 38200 La Laguna, Spain; [email protected] 
 Department of Traumatology, Hospital Universitario Marqués de Valdecilla, University of Cantabria, 39008 Santander, Spain; [email protected] 
 Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, University of Cantabria, 39012 Santander, Spain; [email protected] 
First page
1277
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
19994923
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2565488024
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.