Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells

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)...

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Autores: Cabrera Pérez, Raquel, Carreras-Sánchez, Irene, Roig Molina, Ángela, López-Fernández, Alba, Portas-Torres, Irene, Batlle Morera, Laura, Vélez-Grajales, Roberto, Vives, Joaquim
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/71406
Acceso en línea:http://hdl.handle.net/10230/71406
http://dx.doi.org/10.3390/cells14120862
Access Level:acceso abierto
Palabra clave:Wharton’s jelly
Advanced therapy medicinal product
Bone regeneration
Fibrin
Multipotent mesenchymal stromal cells
Synthetic bone substitute
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spelling Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cellsCabrera Pérez, RaquelCarreras-Sánchez, IreneRoig Molina, ÁngelaLópez-Fernández, AlbaPortas-Torres, IreneBatlle Morera, LauraVélez-Grajales, RobertoVives, JoaquimWharton’s jellyAdvanced therapy medicinal productBone regenerationFibrinMultipotent mesenchymal stromal cellsSynthetic bone substituteSecondary 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.MDPI202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/71406http://dx.doi.org/10.3390/cells14120862reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésCells. 2025 Jun 7;14(12):862© 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/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/714062026-06-12T07:21:37Z
dc.title.none.fl_str_mv Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
title Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
spellingShingle Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
Cabrera Pérez, Raquel
Wharton’s jelly
Advanced therapy medicinal product
Bone regeneration
Fibrin
Multipotent mesenchymal stromal cells
Synthetic bone substitute
title_short Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
title_full Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
title_fullStr Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
title_full_unstemmed Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
title_sort Preclinical assessment in juvenile sheep of an allogeneic bone tissue engineering product with Wharton's jelly mesenchymal stromal cells
dc.creator.none.fl_str_mv Cabrera Pérez, Raquel
Carreras-Sánchez, Irene
Roig Molina, Ángela
López-Fernández, Alba
Portas-Torres, Irene
Batlle Morera, Laura
Vélez-Grajales, Roberto
Vives, Joaquim
author Cabrera Pérez, Raquel
author_facet Cabrera Pérez, Raquel
Carreras-Sánchez, Irene
Roig Molina, Ángela
López-Fernández, Alba
Portas-Torres, Irene
Batlle Morera, Laura
Vélez-Grajales, Roberto
Vives, Joaquim
author_role author
author2 Carreras-Sánchez, Irene
Roig Molina, Ángela
López-Fernández, Alba
Portas-Torres, Irene
Batlle Morera, Laura
Vélez-Grajales, Roberto
Vives, Joaquim
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Wharton’s jelly
Advanced therapy medicinal product
Bone regeneration
Fibrin
Multipotent mesenchymal stromal cells
Synthetic bone substitute
topic Wharton’s jelly
Advanced therapy medicinal product
Bone regeneration
Fibrin
Multipotent mesenchymal stromal cells
Synthetic bone substitute
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/71406
http://dx.doi.org/10.3390/cells14120862
url http://hdl.handle.net/10230/71406
http://dx.doi.org/10.3390/cells14120862
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cells. 2025 Jun 7;14(12):862
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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