Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment

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• dc.contributor.author Cabrera Pérez, Raquel
• dc.contributor.author Ràfols Mitjans, Alexis
• dc.contributor.author Roig Molina, Ángela
• dc.contributor.author Beltramone, Silvia
• dc.contributor.author Vives, Joaquim
• dc.contributor.author Batlle Morera, Laura
• dc.date.accessioned 2024-02-09T07:49:56Z
• dc.date.available 2024-02-09T07:49:56Z
• dc.date.issued 2023
• dc.description.abstract Background: Wharton's Jelly (WJ) Mesenchymal Stromal Cells (MSC) have emerged as an attractive allogeneic therapy for a number of indications, except for bone-related conditions requiring new tissue formation. This may be explained by the apparent recalcitrance of MSC,WJ to differentiate into the osteogenic lineage in vitro, as opposed to permissive bone marrow (BM)-derived MSCs (MSC,BM) that readily commit to bone cells. Consequently, the actual osteogenic in vivo capacity of MSC,WJ is under discussion. Methods: We investigated how physiological bone environments affect the osteogenic commitment of recalcitrant MSCs in vitro and in vivo. To this end, MSC of BM and WJ origin were co-cultured and induced for synchronous osteogenic differentiation in vitro using transwells. For in vivo experiments, immunodeficient mice were injected intratibially with a single dose of human MSC and bone formation was evaluated after six weeks. Results: Co-culture of MSC,BM and MSC,WJ resulted in efficient osteogenesis in both cell types after three weeks. However, MSC,WJ failed to commit to bone cells in the absence of MSC,BM's osteogenic stimuli. In vivo studies showed successful bone formation within the medullar cavity of tibias in 62.5% of mice treated with MSC, WJ. By contrast, new formed trabeculae were only observed in 25% of MSC,BM-treated mice. Immunohistochemical staining of human COXIV revealed the persistence of the infused cells at the site of injection. Additionally, cells of human origin were also identified in the brain, heart, spleen, kidney and gonads in some animals treated with engineered MSC,WJ (eMSC,WJ). Importantly, no macroscopic histopathological alterations, ectopic bone formation or any other adverse events were detected in MSC-treated mice. Conclusions: Our findings demonstrate that in physiological bone microenvironment, osteogenic commitment of MSC,WJ is comparable to that of MSC,BM, and support the use of off-the-shelf allogeneic MSC,WJ products in bone repair and bone regeneration applications.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cabrera-Pérez R, Ràfols-Mitjans A, Roig-Molina Á, Beltramone S, Vives J, Batlle-Morera L. Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment. J Transl Med. 2023 Nov 10;21(1):802. DOI: 10.1186/s12967-023-04672-9
• dc.identifier.doi http://dx.doi.org/10.1186/s12967-023-04672-9
• dc.identifier.issn 1479-5876
• dc.identifier.uri http://hdl.handle.net/10230/59045
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof J Transl Med. 2023 Nov 10;21(1):802
• dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Advanced therapy medicinal product
• dc.subject.keyword Bone microenvironment
• dc.subject.keyword Bone regeneration
• dc.subject.keyword Multipotent mesenchymal stromal cells
• dc.subject.keyword Regenerative medicine
• dc.subject.keyword Wharton’s jelly
• dc.title Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion