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The authors would like to acknowledge Dr Anna Bigas for kindly providing NSG mice and the Tissue Engineering Unit and The Core Facilities Program at CRG for technical support.

Analysis of institutional authors

Ràfols-Mitjans, AAuthorBeltramone, SAuthorBatlle-Morera, LCorresponding Author
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Human Wharton's jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment

Publicated to:Journal Of Translational Medicine. 21 (1): 802- - 2023-11-10 21(1), DOI: 10.1186/s12967-023-04672-9

Authors: Cabrera-Pérez, R; Ràfols-Mitjans, A; Roig-Molina, A; Beltramone, S; Vives, J; Batlle-Morera, L

Affiliations

Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Gene Regulat Stem Cells & Canc Program, Barcelona 08003, Catalonia, Spain - Author
Serv Terapia Cellular i Avancada, Blood & Tissue Bank BST, Barcelona 08005, Catalonia, Spain - Author
Univ Autonoma Barcelona UAB, Med Dept, Barcelona 08193, Catalonia, Spain - Author
Vall dHebron Res Inst VHIR, Musculoskeletal Tissue Engn Grp, Barcelona 08035, Catalonia, Spain - Author

Abstract

BackgroundWharton'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.MethodsWe 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.ResultsCo-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.ConclusionsOur 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.

Keywords
advanced therapy medicinal productbone microenvironmentbone regenerationmultipotent mesenchymal stromal cellsregenerative medicineAdipose-tissueAdvanced therapy medicinal productBone microenvironmentBone regenerationDifferentiationDiseaseMarrowMultipotent mesenchymal stromal cellsRegenerative medicineStem-cellsTherapyWharton's jellyWharton’s jelly

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Translational Medicine due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 29/189, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, Research & Experimental.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-05-13:

  • WoS: 2
  • Scopus: 2
  • Europe PMC: 1
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-13:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 11.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 11 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 11.1.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (BATLLE, LAURA).

the author responsible for correspondence tasks has been BATLLE, LAURA.