Multiple Differentiation Capacity of STRO-1⁺/CD146⁺PDL Mesenchymal Progenitor Cells

Abstract

Although mesenchymal progenitor cells can be isolated from periodontal ligament (PDL) tissues using stem cell markers STRO-1 and CD146, the proportion of these cells that have the capacity to differentiate into multiple cell lineages remains to be determined. This study was designed to quantify the proportions of primary human PDL cells that can undergo multi-lineage differentiation, and to compare the magnitude of these capabilities relative to bone marrow-derived mesenchymal stem cells (MSC) and parental PDL (PPDL) cells. PDL mesenchymal progenitor (PMP) cells were isolated from PPDL cells using the markers STRO-1 and CD146. The colony-forming efficiency and multi-lineage differentiation potential of PMP, PPDL, and MSCs under chondrogenic, osteogenic and adipogenic conditions were determined. Flow cytometry revealed that on average 2.6% of PPDL cells were STRO-1+/CD146+, whereas more than 63% were STRO-1-/CD146-. Colony-forming efficiency of STRO-1+/CD146+ PMP cells (19.3%) and MSCs (16.7%) was significantly higher than that of PPDL cells (6.8%). Cartilage specific genes, early markers of osteoblastic differentiation, and adipogenic markers were significantly up-regulated under appropriate conditions in PMP cells and MSCs compared to either their non-induced counterparts or induced PPDL cells. Consistent with these findings, immunohistochemistry revealed substantial accumulation of cartilaginous macromolecules, mineralized calcium nodules, and lipid vacuoles under chondrogenic, osteogenic or adipogenic conditions in PMP and MSC cultures, respectively, compared to non-induced controls or induced PPDL cells. Thus, STRO-1+/CD146+ PMP cells demonstrate multi-lineage differentiation capacity comparable in magnitude to MSCs, and could potentially be utilized for regeneration of the periodontium and other tissues.

Retraction：Polyphosphate-induced matrix metalloproteinase-13 is required for osteoblast-like cell differentiation in human adipose tissue derived mesenchymal stem cells

“…The levels of MMP-13 mRNA expression in Poly(P)-treated cells were significantly increased (p < 0.05) at days 3, 5, and 7 of culture ( Figure 3A). Bone-associated cells also express other MMPs including MMP-1, MMP-2, MMP-3, and MMP-9 (34)(35)(36). However, we found no significant changes in their expression levels in hAT-MSCs treated with 0.2 mM Poly(P) ( Figure 3B).…”

Retraction: Polyphosphate-induced matrix metalloproteinase-3-mediated proliferation in rat dental pulp fibroblast-like cells is mediated by a Wnt5 signaling cascade

“…Bone-associated cells also express other MMPs such as MMP-1, MMP-2, MMP-9, and MMP-13 (38,39). Although we assessed whether other MMPs were induced by 0.1 mM Poly(P) in DPFCs, except for MMP-3, there were no significant increases in their mRNA or protein expression in DPFCs (Figures 2E and 2F).…”

Periodontal Ligament Stem Cells

“…Lindroos et al (2008) also reported the expressions of CD13, CD 29, CD44, CD90, CD105, and CD166 in human PDLSCs. Cell line 1-11 expressed other MSC markers, STRO-1 and CD146/MUC18, whereas cell line 1-17 contained STRO-1 only (data not shown), although these markers are also believed to be expressed in human and mouse PDLSCs (Seo et al, 2004;Xu et al, 2009). On the other hand, cell line 1-17 intensely expressed ES cell marker genes, OCT-4 and Nanog, whereas cell line 1-11 expressed these markers weakly (Fig.…”

“…Several studies have reported that PDLSCs express cell surface markers, such as STRO-1 (putative stem cell marker), CD146 (perivascular cell marker), STRO-3 (tissue nonspecific ALP), CD13, CD29 (integrin β-1), CD44, CD90 (Thy-1), CD105 (endoglin), CD106 (VCAM-1), and CD166 (ALCAM) (Nagatomo et al, 2006;Seo et al, 2004;Trubiani et al, 2005;Wada et al, 2009), similar to BMMSCs (Shi & Gronthos 2003;Gronthos et al, 2007), as well as embryonic markers, including OCT-4, SSEA-1 and SSEA-4 (Trubiani et al, 2010). PDLSCs have so far been isolated from PDL heterogeneous cell populations using STRO-1 and CD146 antibodies (Seo et al, 2004), although the percentage of STRO-1-positive cells in the PDL tissue is reportedly not to be very high (STRO-1 positive cells: 1.2-7.68%) (Nagatomo et al, 2006;Xu et al, 2009). Additionally, PDLSCs express a PDL marker, scleraxis, suggesting that PDLSCs may belong to a unique population of MSCs.…”