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

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 in...

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Autores: Cabrera Pérez, Raquel, Ràfols Mitjans, Alexis, Roig Molina, Ángela, Beltramone, Silvia, Vives, Joaquim, Batlle Morera, Laura
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Universitat Pompeu Fabra
Repositório:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/59045
Acesso em linha:http://hdl.handle.net/10230/59045
http://dx.doi.org/10.1186/s12967-023-04672-9
Access Level:Acceso aberto
Palavra-chave:Advanced therapy medicinal product
Bone microenvironment
Bone regeneration
Multipotent mesenchymal stromal cells
Regenerative medicine
Wharton’s jelly
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spelling Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironmentCabrera Pérez, RaquelRàfols Mitjans, AlexisRoig Molina, ÁngelaBeltramone, SilviaVives, JoaquimBatlle Morera, LauraAdvanced therapy medicinal productBone microenvironmentBone regenerationMultipotent mesenchymal stromal cellsRegenerative medicineWharton’s jellyBackground: 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.BioMed Central202420242023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/59045http://dx.doi.org/10.1186/s12967-023-04672-9reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésJ Transl Med. 2023 Nov 10;21(1):802© 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/590452026-06-12T07:21:37Z
dc.title.none.fl_str_mv Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
title Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
spellingShingle Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
Cabrera Pérez, Raquel
Advanced therapy medicinal product
Bone microenvironment
Bone regeneration
Multipotent mesenchymal stromal cells
Regenerative medicine
Wharton’s jelly
title_short Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
title_full Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
title_fullStr Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
title_full_unstemmed Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
title_sort Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
dc.creator.none.fl_str_mv Cabrera Pérez, Raquel
Ràfols Mitjans, Alexis
Roig Molina, Ángela
Beltramone, Silvia
Vives, Joaquim
Batlle Morera, Laura
author Cabrera Pérez, Raquel
author_facet Cabrera Pérez, Raquel
Ràfols Mitjans, Alexis
Roig Molina, Ángela
Beltramone, Silvia
Vives, Joaquim
Batlle Morera, Laura
author_role author
author2 Ràfols Mitjans, Alexis
Roig Molina, Ángela
Beltramone, Silvia
Vives, Joaquim
Batlle Morera, Laura
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Advanced therapy medicinal product
Bone microenvironment
Bone regeneration
Multipotent mesenchymal stromal cells
Regenerative medicine
Wharton’s jelly
topic Advanced therapy medicinal product
Bone microenvironment
Bone regeneration
Multipotent mesenchymal stromal cells
Regenerative medicine
Wharton’s jelly
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
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/10230/59045
http://dx.doi.org/10.1186/s12967-023-04672-9
url http://hdl.handle.net/10230/59045
http://dx.doi.org/10.1186/s12967-023-04672-9
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv J Transl Med. 2023 Nov 10;21(1):802
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 BioMed Central
publisher.none.fl_str_mv BioMed Central
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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