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Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration
Open accessAbstract
Umbilical cord mesenchymal stem cells (UC-MSCs) show properties similar to bone marrow mesenchymal stem cells (BM-MSCs), although controversial data exist regarding their osteogenic potential. We prepared clinical-grade UC-MSCs from Wharton's Jelly and we investigated if UC-MSCs could be used as substitutes for BM-MSCs in muscoloskeletal regeneration as a more readily available and functional source of MSCs. UC-MSCs were loaded onto scaffolds and implanted subcutaneously (ectopically) and in critical-sized calvarial defects (orthotopically) in mice. For live cell-tracking experiments, UC-MSCs were first transduced with the luciferase gene. Angiogenic properties of UC-MSCs were tested using the mouse metatarsal angiogenesis assay. Cell secretomes were screened for the presence of various cytokines using an array assay. Analysis of implanted scaffolds showed that UC-MSCs, contrary to BM-MSCs, remained detectable in the implants for 3 weeks at most and did not induce bone formation in an ectopic location. Instead, they induced a significant increase of blood vessel ingrowth. In agreement with these observations, UC-MSC-conditioned medium presented a distinct and stronger proinflammatory/chemotactic cytokine profile than BM-MSCs and a significantly enhanced angiogenic activity. When UC-MSCs were orthotopically transplanted in a calvarial defect, they promoted increased bone formation as well as BM-MSCs. However, at variance with BM-MSCs, the new bone was deposited through the activity of stimulated host cells, highlighting the importance of the microenvironment on determining cell commitment and response. Therefore, we propose, as therapy for bone lesions, the use of allogeneic UC-MSCs by not depositing bone matrix directly, but acting through the activation of endogenous repair mechanisms.
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“Simultaneously, MSCs contribute to new vessel formation, further enhancing fracture healing [39,82].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [82]
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Metadata
- Authors
- Todeschi, M. R., El Backly, R., Capelli, C., Daga, A., Patrone, E., Introna, M., Cancedda, R., & Mastrogiacomo, M.
- Affiliations
- University of Genoa (IT)
- Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy.
- Ospedale Papa Giovanni XXIII (IT)
- Ospedale Policlinico San Martino (IT)
- Corresponding author
- Mastrogiacomo, Maddalena
- Venue
- Stem Cells and Development
- Publisher
- SAGE Publications
- Published
- 2015-07
- Volume
- 24
- Issue
- 13
- Pages
- 1570-1581
- ISSN
- 1525-8165 (ISSN-L)
- 1547-3287
- 1557-8534
- PMC
- PMC4499786
- OpenAlex
- W2005472583
- Cited by
- 103
- References
- 60
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 10 · 2021: 7 · 2020: 12 · 2019: 14 · 2018: 10 · 2017: 12 · 2016: 9 · 2015: 5
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stem Cells and Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- Regione Liguria
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Keywords
- human umbilical cord mesenchymal stem cells, Wharton's jelly, bone regeneration, angiogenesis, calvarial defect, bone marrow mesenchymal stem cells, cell microenvironment, secretome, inflammatory cytokines, cell tracking, allogeneic cell therapy, scaffold implantation
- MeSH terms
- Animals, Bone Regeneration, Cells, Cultured, Female, Humans, Umbilical Cord, Neovascularization, Physiologic, Mesenchymal Stem Cell Transplantation, Mice, Tissue Scaffolds, Stem Cell Niche, Mesenchymal Stem Cells
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