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Abstract: The evidence sustaining the regenerative properties of mesenchymal stem cells? (MSCs) secretome has prompted a paradigm change, where MSCs have shifted from being considered direct contributors to tissue regeneration toward being seen as cell factories for producing biotech medicines. We have previously designed a method to prime MSCs towards osteogenic differentiation by silencing the Wnt/?-Catenin inhibitor Sfpr1. This approach produces a significant increase in bone formation in osteoporotic mice. In this current work, we set to investigate the contribution of the secretome from the MSCs where Sfrp1 has been silenced, to the positive effect seen on bone regeneration in vivo. The conditioned media (CM) of the murine MSCs line C3H10T1/2, where Sfrp1 has been transiently silenced (CM-Sfrp1), was found to induce, in vitro, an increase in the osteogenic differentiation of this same cell line, as well as a decrease of the expression of the Wnt inhibitor Dkk1 in murine osteocytes ex vivo. A reduction in the RANKL/OPG ratio was also detected ex vivo, suggesting a negative effect of CM-Sfrp1 on osteoclastogenesis. Moreover, this CM significantly increases the mineralization of human primary MSCs isolated from osteoportotic patients in vitro. Proteomic analysis identified enrichment of proteins involved in osteogenesis within the soluble and vesicular fractions of this secretome. Altogether, we demonstrate the pro-osteogenic potential of the secretome of MSCs primmed in this fashion, suggesting that this is a valid approach to enhance the osteo-regenerative properties of MSCs' secretome
Fuente: International journal of molecular sciences, 2023, 24(15), 12399
Publisher: MPDI
Year of publication: 2023
No. of pages: 15
Publication type: Article
DOI: 10.3390/ijms241512399
ISSN: 1661-6596,1422-0067
Publication Url: https://doi.org/10.3390/ijms241512399
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GARCÍA-SÁNCHEZ, DANIEL
ALBERTO GONZALEZ GONZALEZ
ÁLVAREZ-IGLESIAS, ITZÍAR
BOLADO-CARRANCIO, ALFONSO
CERTO, MATILDE
MARIA ISABEL PEREZ NUÑEZ
JOSE ANTONIO RIANCHO MORAL
JOSE CARLOS RODRIGUEZ REY
DELGADO-CALLE, JESÚS
FLOR MARIA PEREZ CAMPO
MÓNICA DEL DUJO GUTIÉRREZ
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