The central role of Mesenchymal Stem Cells (MSC) in Regenerative Medicine derives, in large part, from their ability to differentiate into different cell types. The induction of proliferation and differentiation to osteoblasts of MSCs forms the basis of bone regenerative therapies. Osteogenic differentiation of MSCs is a complex process regulated simultaneously by different signaling routes, among which the BMP route stands out.
The Smurf1 gene encodes a Ubiquitin ligase that participates in the regulation of the BMP pathway. By silencing this gene in MSC with lentiviral vectors, members of the Mineral and Lipid Metabolism group (https://grupoitcantabria.wixsite.com/inicio) in collaboration with the Department of Pharmaceutical Technology of the University of La Laguna demonstrated a significant improvement in bone formation in vivo in a rat calvaria model [ one].
In this new work, published in the journal Stem Cells Translational Medicine [2], the same authors demonstrate that it is possible to achieve the same effect by transfecting MSCs seeded in alginate-BMP scaffolds with anti-sense oligonucleotides (Gapmers). In addition, the combination of controlled release of BMP and the silencing of Smurf1 allows the use of BMP amounts one million times lower than those currently used in the clinic. It is noteworthy that Gapmers are DNA molecules previously approved by the FDA for other processes, which would undoubtedly facilitate a possible subsequent clinical development. Finally, the demonstrated usefulness of this procedure in MSC cultures of osteoporosis patients suggests that the development of new particles based on this strategy could also be useful in the treatment of systemic diseases of the bone system.
Reference
García-García P, Ruiz M, Reyes R, Delgado A, Évora C, Riancho JA, Rodríguez-Rey JC, Pérez-Campo FM. Smurf1 Silencing Using a LNA-ASOs/Lipid Nanoparticle System to Promote Bone Regeneration. Stem Cells Transl Med. 2019 Oct 21. doi: 10.1002/sctm.19-0145. [Epub ahead of print] PubMed PMID: 31631568.
