CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment

Abstract

Bone marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacity and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146−/Low and CD146High cells under clonal conditions and after sorting of the non-clonal cell population to determine whether this expression is associated with specific functions. CD146−/Low and CD146High bone marrow MSCs did not differ in colony-forming unit-fibroblast number, osteogenic, adipogenic and chondrogenic differentiation or in vitro haematopoietic-supportive activity. However, CD146−/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment to a vascular smooth muscle cell (VSMC) lineage characterized by a strong up-regulation of calponin-1 and SM22α expression and an ability to contract collagen matrix. Thus, within a bone marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed towards a VSMC lineage.

Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction

“…These multiple bands are the result of extracellular processing of the NG2 proteoglycan that may then regulate signaling as well as migration (31). We again identified increased gene and protein expression of the Wnt/β-catenin target WNT1-inducible signaling pathway protein 1 (Wisp1) (Figure 2, A Figure 4H), which is associated with pericyte or endothelial lineage specification from MPCs (33,34). βOE MPCs also had decreased expression of CD105 (also known as endoglin), indicative of an attenuated potential for terminal myogenic or α-SMC differentiation and increased invasiveness (35,36).…”

Downregulation of Melanoma Cell Adhesion Molecule (MCAM/CD146) Accelerates Cellular Senescence in Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

“…Results from several studies have shown that CD146 augments motility, metastasis, and tumorigenesis of cancer cells, including melanoma and breast cancer cells [42,43]. Recently, growing evidence has indicated that CD146 expression is related to the multilineage differentiation potential, proliferation, and stemness of MSCs [44][45][46][47][48][49]. Indeed, we also observed that CD146 downregulation led to decreases in the osteogenic and adipogenic differentiation potential of hUCBMSCs, implying that such multilineage differentiation potential depends on CD146 expression levels in hUCB-MSCs (supplemental online Figs.…”

Adult Stem Cell Subsets from Adult Human Dermis

“…Previous research has revealed that a subset of Primary Human Adherent Dermal Cells (PHADs) expressing Stage Specific Embryonic Antigen-3 (SSEA-3) are transcriptionally Similar to Adipocyte-Derived Stem Cells (AdSc) [9]. Human cells expressing CD146 derived from diverse sources have been shown to differentiate in vitro not only into osteoblasts, chondrocytes, and adipocytes [38] but also into hepatocyte-like cells [39] and smooth muscle [40]. CD271 is an epitope that was initially identified in situ in skin punch biopsies and characterized as a strong hMSC marker over adherent dermal cells [11].…”