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Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration
- Source :
- Stem cells and development. 24(13)
- Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Bone Regeneration
Angiogenesis
Cell
Neovascularization, Physiologic
Biology
Mesenchymal Stem Cell Transplantation
Umbilical cord
Proinflammatory cytokine
Umbilical Cord
Neovascularization
Mice
Original Research Reports
medicine
Animals
Humans
Stem Cell Niche
Bone regeneration
Cells, Cultured
Tissue Scaffolds
Regeneration (biology)
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Hematology
Cell biology
medicine.anatomical_structure
Immunology
Female
medicine.symptom
Developmental Biology
Subjects
Details
- ISSN :
- 15578534
- Volume :
- 24
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Stem cells and development
- Accession number :
- edsair.doi.dedup.....9987c9aa86bc9fee0c912c2366debfbf