Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
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- dc.contributor.author Cabrera Pérez, Raquel
- dc.contributor.author Carreras-Sánchez, Irene
- dc.contributor.author Roig Molina, Ángela
- dc.contributor.author López-Fernández, Alba
- dc.contributor.author Portas-Torres, Irene
- dc.contributor.author Batlle Morera, Laura
- dc.contributor.author Vélez-Grajales, Roberto
- dc.contributor.author Vives, Joaquim
- dc.date.accessioned 2025-10-07T05:36:44Z
- dc.date.available 2025-10-07T05:36:44Z
- dc.date.issued 2025
- dc.description.abstract Secondary osteonecrosis (ON) is a common complication in paediatric cancer survivors. Combining multipotent mesenchymal stromal cells (MSCs) with core decompression surgery halts disease progression and stimulates bone regeneration. However, the success of advanced therapy medicinal products (ATMPs) requires versatile "off-the-shelf" tissue engineering products (TEPs). This study evaluated the safety and efficacy of TEPs loaded with allogeneic MSCs from Wharton's jelly (WJ-MSCs) in a large-animal model of bone regeneration to support a paediatric investigational plan for ON patients. WJ-MSC-laden fibrin-based hydrogels combined with a synthetic bone substitute (PRO-DENSETM) were tested in 16 juvenile sheep (8 males and 8 females) distributed in four experimental groups. Each animal received four cylindrical bone defects in the femoral and tibial epiphyses and was assessed at 6 and 12 weeks. Safety was confirmed, and bone regeneration was observed across all groups. A combination of WJ-MSCs with PRO-DENSETM led to improved histological scores, osteogenesis, and construct integration. Trabecular bone volume also increased more in cellular groups over time. However, effects were inconsistent across groups, reflecting the variability seen in clinical trials and highlighting the significant impact of factors such as immunogenetic compatibility, MSC batch potency, and interaction with the recipient's microenvironment on the therapeutic effectiveness and successful clinical translation of allogeneic ATMPs.
- dc.format.mimetype application/pdf
- dc.identifier.citation Cabrera-Pérez R, Carreras-Sánchez I, Roig-Molina Á, López-Fernández A, Portas-Torres I, Batlle-Morera L, et al. Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells. Cells. 2025 Jun 7;14(12):862. DOI: 10.3390/cells14120862
- dc.identifier.doi http://dx.doi.org/10.3390/cells14120862
- dc.identifier.issn 2073-4409
- dc.identifier.uri http://hdl.handle.net/10230/71406
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Cells. 2025 Jun 7;14(12):862
- dc.rights © 2025 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Wharton’s jelly
- dc.subject.keyword Advanced therapy medicinal product
- dc.subject.keyword Bone regeneration
- dc.subject.keyword Fibrin
- dc.subject.keyword Multipotent mesenchymal stromal cells
- dc.subject.keyword Synthetic bone substitute
- dc.title Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion