Stem Cell Reviews and Reports

, Volume 12, Issue 5, pp 592–603 | Cite as

CD146 Expression Influences Periapical Cyst Mesenchymal Stem Cell Properties

  • Francesco Paduano
  • Massimo Marrelli
  • Francesca Palmieri
  • Marco TatulloEmail author


Recent studies have identified a new human dental derived progenitor cell population with multi-lineage differentiation potential referred to as human periapical cyst mesenchymal stem cells (hPCy-MSCs). In the present study, we compared two subpopulations of hPCy-MSCs characterised by the low or high expression of CD146 to establish whether this expression can regulate their stem cell properties. Using flow cytometry, we evaluated the stem cell marker profile of hPCy-MSCs during passaging. Furthermore, CD146Low and CD146High cells were sorted by magnetic beads and subsequently both cell populations were evaluated for differences in their proliferation, self-renewal, stem cell surface markers, stemness genes expression and osteogenic differentiation potential.

We found that hPCy-MSCs possessed a stable expression of several mesenchymal stem cell surface markers, whereas CD146 expression declined during passaging.

In addition, sorted CD146Low cells proliferated significantly faster, displayed higher colony-forming unit-fibroblast capacity and showed higher expression of Klf4 when compared to the CD146High subset. Significantly, the osteogenic potential of hPCy-MSCs was greater in the CD146Low than in CD146High population. These results demonstrate that CD146 is spontaneously downregulated with passaging at both mRNA and protein levels and that the high expression of CD146 reduces the proliferative, self-renewal and osteogenic differentiation potential of hPCy-MSCs. In conclusion, our study demonstrates that changes in the expression of CD146 can influence the stem cell properties of hPCy-MSCs.


Dental stem cells (DSCs) Human periapical cyst mesenchymal stem cells (hPCy-MSCs) CD146 MSC surface markers Magnetic cell sorting Stemness genes Osteogenic differentiation 



The present study was supported by “ICARE Project - Infrastruttura Calabrese per la medicina Rigenerativa: “Generazione di biobanche per la criopreservazione di cellule staminali umane e di tessuto osseo per uso clinico e design e sviluppo di bioscaffold innovativi”. PON03PE_00009_2.2. The authors are grateful to Dr. Raghavendra Vasudeva Murthy and Dr. Pasquale Marrazzo for editing the manuscript.

Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no conflicts of interest.

Supplementary material

12015_2016_9674_Fig6_ESM.gif (48 kb)
Supplementary Fig. 1

MSC surface marker expression on dental stem cells (DSCs) from various passages. Surface marker expression levels of CD146, CD13, CD29, CD44, CD73, CD90, CD105 and CD45 in a dental pulp stem cells (DPSCs), b dental follicle stem cells (DFPCs) and c periodontal ligament stem cells (PDLSCs) during various passages (p2, p4, p6, p8). (GIF 48 kb)

12015_2016_9674_MOESM1_ESM.tif (642 kb)
High Resolution Image (TIFF 642 kb)
12015_2016_9674_Fig7_ESM.gif (177 kb)
Supplementary Fig. 2

Growth kinetics and the osteogenic potential of hPCy-MSCs during expansion in vitro. a Long term growth curves of hPCy-MSCs, each obtained from an individual donor (n = 8). b Osteogenic differentiation of hPCy-MSCs at passage 0 and passage 10. Cells were exposed to osteogenic induction medium for 3 weeks, followed by staining with Alizarin Red. (GIF 176 kb)

12015_2016_9674_MOESM2_ESM.tif (2.7 mb)
High Resolution Image (TIFF 2713 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Francesco Paduano
    • 1
  • Massimo Marrelli
    • 2
  • Francesca Palmieri
    • 1
  • Marco Tatullo
    • 1
    Email author
  1. 1.Tecnologica Research Institute, Biomedical SectionCrotoneItaly
  2. 2.Calabrodental SRL, Experimental Medicine SectionCrotoneItaly

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