Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) represent a heterogeneous group of multipotent stem cells that could be found in various somatic tissues. MSCs are defined by molecular and functional features including spindle-shape morphology, adherence to plastic surfaces, expression of specific surface markers and differentiation potential to chondrocytes, adipocytes and osteocytes. The surface markers were proposed to affect the differentiation potential of MSCs by a limited number of studies. Endoglin (CD105) is defined to be a significant marker for osteogenic and chondrogenic differentiation ability of MSCs. Low CD105 expression is associated with increased osteogenic potential while high CD105 expression is correlated with strong chondrogenic potential. Myrtucommulone-A (MC-A) is an active compound with various biological effects on different cell types but its effect on MSC differentiation has not been described yet. In the present study we aimed at investigating the longterm effects of MC-A on hMSCs. MC-A-treatment reduced CD105 expression in distinct human mesenchymal stem cell (hMSC) lines and gave rise to CD105 low population but did not change CD44, CD90 or CD73 expression. The decrease in CD105 expression reduced the chondrogenic potential of hMSCs subsequently while adipogenic or osteogenic differentiation was not affected dramatically. MC-A-treatment also suppressed the NF-jB p65 activation which might be responsible for the reduced chondrogenic potential. Our findings suggest that MC-A could be used to enrich CD105 low hMSCs without the need for cell sorting or changing culture conditions which could be utilised in targeted differentiation studies.

Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’

“…Jiang et al found that CD105(+) ADSC subpopulation in in vitro culture had a much stronger chondrogenic potential than CD105(−) subpopulation and had more intensive immunostaining of type II collagen and higher gene expression of COL2A1 and ACAN following chondrogenic induction 40 . There is also a report that myrtucommulone-A treatment reduced CD105 expression in expanded human ADSCs along with reduced chondrogenic potential 41 .…”

Immortalizing Mesenchymal Stromal Cells from Aged Donors While Keeping Their Essential Features

“…The lower quality of cartilage-like tissue produced by iMSC#6 and iMSC#9 in comparison with T-MSC#6 could be suggested as a result of its lower CD105 positivity, as it is part of the TGF-ß receptor complex. However, it has been noted that CD105 + MSCs have no superior chondrogenic potential than the CD105ones [68], even though it is still controversial [69]. It has also been stated that, as a counterpart of decreased chondrogenic potential, CD105 -MSCs show increased osteogenic potential [69] as a result of superior adhesion and mineralization efficiency [70], which might be related to the superior osteogenic potential of iMSCs.…”

“…However, it has been noted that CD105 + MSCs have no superior chondrogenic potential than the CD105ones [68], even though it is still controversial [69]. It has also been stated that, as a counterpart of decreased chondrogenic potential, CD105 -MSCs show increased osteogenic potential [69] as a result of superior adhesion and mineralization efficiency [70], which might be related to the superior osteogenic potential of iMSCs. Nevertheless, surface marker expression does not necessarily reflect the functional capacities of MSC [63], and the inferior osteogenic potential of primary MSC#6 may be also due to them being differentiated at the 6th passage, when cells are expected to be aged [5,71].…”

Structures and Bioactive Properties of Myrtucommulones and Related Acylphloroglucinols from Myrtaceae

“…Treatment with this product reduced the chondrogenic potential in human mesenchymal stem cell (hMSC) lines, possibly as a consequence of the NF-κB p65 activation, while the adipogenic or osteogenic differentiation was not dramatically affected. The exploitation of these properties could be useful in targeted differentiation studies [113].…”