Cargando…

Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing

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 s...

Descripción completa

Detalles Bibliográficos
Autores principales: García-Sánchez, Daniel, González-González, Alberto, García-García, Patricia, Reyes, Ricardo, Pérez-Núñez, María Isabel, Riancho, José A., Évora, Carmen, Rodríguez-Rey, José Carlos, Pérez-Campo, Flor M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398380/
https://www.ncbi.nlm.nih.gov/pubmed/34452242
http://dx.doi.org/10.3390/pharmaceutics13081277
_version_ 1783744825769590784
author García-Sánchez, Daniel
González-González, Alberto
García-García, Patricia
Reyes, Ricardo
Pérez-Núñez, María Isabel
Riancho, José A.
Évora, Carmen
Rodríguez-Rey, José Carlos
Pérez-Campo, Flor M.
author_facet García-Sánchez, Daniel
González-González, Alberto
García-García, Patricia
Reyes, Ricardo
Pérez-Núñez, María Isabel
Riancho, José A.
Évora, Carmen
Rodríguez-Rey, José Carlos
Pérez-Campo, Flor M.
author_sort García-Sánchez, Daniel
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8398380
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83983802021-08-29 Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing García-Sánchez, Daniel González-González, Alberto García-García, Patricia Reyes, Ricardo Pérez-Núñez, María Isabel Riancho, José A. Évora, Carmen Rodríguez-Rey, José Carlos Pérez-Campo, Flor M. Pharmaceutics Article 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. MDPI 2021-08-17 /pmc/articles/PMC8398380/ /pubmed/34452242 http://dx.doi.org/10.3390/pharmaceutics13081277 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
García-Sánchez, Daniel
González-González, Alberto
García-García, Patricia
Reyes, Ricardo
Pérez-Núñez, María Isabel
Riancho, José A.
Évora, Carmen
Rodríguez-Rey, José Carlos
Pérez-Campo, Flor M.
Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing
title Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing
title_full Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing
title_fullStr Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing
title_full_unstemmed Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing
title_short Effective Osteogenic Priming of Mesenchymal Stem Cells through LNA-ASOs-Mediated Sfrp1 Gene Silencing
title_sort effective osteogenic priming of mesenchymal stem cells through lna-asos-mediated sfrp1 gene silencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398380/
https://www.ncbi.nlm.nih.gov/pubmed/34452242
http://dx.doi.org/10.3390/pharmaceutics13081277
work_keys_str_mv AT garciasanchezdaniel effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT gonzalezgonzalezalberto effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT garciagarciapatricia effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT reyesricardo effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT pereznunezmariaisabel effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT rianchojosea effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT evoracarmen effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT rodriguezreyjosecarlos effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing
AT perezcampoflorm effectiveosteogenicprimingofmesenchymalstemcellsthroughlnaasosmediatedsfrp1genesilencing