Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the in Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

Maria Rosa Todeschi, Rania El Backly, Chiara Capelli, Antonio Daga, Eugenio Patrone, Martino Introna, Ranieri Cancedda, Maddalena Mastrogiacomo

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1570-1581
Number of pages12
JournalStem Cells and Development
Volume24
Issue number13
DOIs
Publication statusPublished - Jul 1 2015

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Bone Regeneration
Umbilical Cord
Mesenchymal Stromal Cells
Bone Marrow
Osteogenesis
Bone and Bones
Wharton Jelly
Cell Tracking
Bone Matrix
Metatarsal Bones
Conditioned Culture Medium
Luciferases
Chemokines

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the in Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration. / Todeschi, Maria Rosa; El Backly, Rania; Capelli, Chiara; Daga, Antonio; Patrone, Eugenio; Introna, Martino; Cancedda, Ranieri; Mastrogiacomo, Maddalena.

In: Stem Cells and Development, Vol. 24, No. 13, 01.07.2015, p. 1570-1581.

Research output: Contribution to journalArticle

Todeschi, Maria Rosa ; El Backly, Rania ; Capelli, Chiara ; Daga, Antonio ; Patrone, Eugenio ; Introna, Martino ; Cancedda, Ranieri ; Mastrogiacomo, Maddalena. / Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the in Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration. In: Stem Cells and Development. 2015 ; Vol. 24, No. 13. pp. 1570-1581.
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