Osteogenic commitment of Wharton's jelly mesenchymal stromal cells: mechanisms and implications for bioprocess development and clinical application

Stem Cell Res Ther. 2019 Nov 28;10(1):356. doi: 10.1186/s13287-019-1450-3.

Abstract

Background: Orthopaedic diseases are one of the major targets for regenerative medicine. In this context, Wharton's jelly (WJ) is an alternative source to bone marrow (BM) for allogeneic transplantation since its isolation does not require an invasive procedure for cell collection and does not raise major ethical concerns. However, the osteogenic capacity of human WJ-derived multipotent mesenchymal stromal cells (MSC) remains unclear.

Methods: Here, we compared the baseline osteogenic potential of MSC from WJ and BM cell sources by cytological staining, quantitative real-time PCR and proteomic analysis, and assessed chemical and biological strategies for priming undifferentiated WJ-MSC. Concretely, different inhibitors/activators of the TGFβ1-BMP2 signalling pathway as well as the secretome of differentiating BM-MSC were tested.

Results: Cytochemical staining as well as gene expression and proteomic analysis revealed that osteogenic commitment was poor in WJ-MSC. However, stimulation of the BMP2 pathway with BMP2 plus tanshinone IIA and the addition of extracellular vesicles or protein-enriched preparations from differentiating BM-MSC enhanced WJ-MSC osteogenesis. Furthermore, greater outcome was obtained with the use of conditioned media from differentiating BM-MSC.

Conclusions: Altogether, our results point to the use of master banks of WJ-MSC as a valuable alternative to BM-MSC for orthopaedic conditions.

Keywords: Bone marrow; Bone regeneration; Mesenchymal stromal cells; Osteogenic differentiation; Wharton’s jelly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Differentiation*
  • Culture Media, Conditioned / pharmacology
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Osteogenesis*
  • Proteomics
  • Real-Time Polymerase Chain Reaction

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Culture Media, Conditioned