Osteogenic Differentiation of Mesenchymal Stromal Cells: A Comparative Analysis Between Human Subcutaneous Adipose Tissue and Dental Pulp

Stem Cells Dev. 2017 Jun 1;26(11):843-855. doi: 10.1089/scd.2016.0190. Epub 2017 Mar 13.

Abstract

White adipose tissue is a source of mesenchymal stromal/stem cells (MSCs) that are actively studied for their possible therapeutic use in bone tissue repair/remodeling. To better appreciate the osteogenic potential of these cells, we compared some properties of MSCs from human subcutaneous adipose tissue [subcutaneous-adipose stromal cells (S-ASCs)] and dental pulp stem cell (DPSCs) of third-impacted molars, the latter representing a well-established MSC source. Both undifferentiated cell types showed similar fibroblast-like morphology and mesenchymal marker expression. However, undifferentiated S-ASCs displayed a faster doubling time coupled to greater proliferation and colony-forming ability than DPSCs. Also, the osteogenic differentiation of S-ASCs was greater than that of DPSCs, as evaluated by the higher levels of expression of early osteogenic markers Runt-related transcription factor-2 (RUNX2) and alkaline phosphatase at days 3-14 and of extracellular matrix mineralization at days 14-21. Moreover, S-ASCs showed a better colonization of the titanium scaffold. In addition, we investigated whether S-ASC osteogenic commitment was enhanced by adenosine A1 receptor (A1R) stimulation, as previously shown for DPSCs. Although A1R expression was constant during DPSC differentiation, it increased in S-ASC at day 21 from osteogenesis induction. Accordingly, A1R stimulation by the agonist 2-chloro-N6-cyclopentyl-adenosine, added to the cultures at each medium change, stimulated proliferation only in differentiating DPSC and enhanced the osteogenic differentiation earlier in DPSCs than in S-ASCs. These effects were counteracted by cell pretreatment with a selective A1R antagonist. Thus, our findings suggest that S-ASCs could be advantageously used in regenerative orthopedics/dentistry, and locally released or exogenously added purines may play a role in bone repair/remodeling, even though this aspect should be more thoroughly evaluated.

Keywords: characteristics of the osteogenic differentiation of S-ASCs; mesenchymal stromal cells from human subcutaneous adipose tissue (S-ASCs); regenerative medicine.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Adolescent
  • Cell Differentiation* / drug effects
  • Cell Lineage / drug effects
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Dental Pulp / cytology*
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / ultrastructure
  • Osteogenesis* / drug effects
  • Phenotype
  • Receptor, Adenosine A1 / metabolism
  • Spectrometry, X-Ray Emission
  • Subcutaneous Fat / cytology*

Substances

  • Receptor, Adenosine A1
  • 2-chloro-N(6)cyclopentyladenosine
  • Adenosine