Abstract
Mesenchymal stromal cells (MSCs) have the potential to differentiate into a variety of mature cell types and are a promising source of regenerative medicine. The success of regenerative medicine using MSCs strongly depends on their differentiation potential. In this study, we sought to identify marker genes for predicting the osteogenic differentiation potential by comparing ilium MSC and fibroblast samples. We measured the mRNA levels of 95 candidate genes in nine ilium MSC and four fibroblast samples before osteogenic induction, and compared them with alkaline phosphatase (ALP) activity as a marker of osteogenic differentiation after induction. We identified 17 genes whose mRNA expression levels positively correlated with ALP activity. The chondrogenic and adipogenic differentiation potentials of jaw MSCs are much lower than those of ilium MSCs, although the osteogenic differentiation potential of jaw MSCs is comparable with that of ilium MSCs. To select markers suitable for predicting the osteogenic differentiation potential, we compared the mRNA levels of the 17 genes in ilium MSCs with those in jaw MSCs. The levels of 7 out of the 17 genes were not substantially different between the jaw and ilium MSCs, while the remaining 10 genes were expressed at significantly lower levels in jaw MSCs than in ilium MSCs. The mRNA levels of the seven similarly expressed genes were also compared with those in fibroblasts, which have little or no osteogenic differentiation potential. Among the seven genes, the mRNA levels of IGF1 and SRGN in all MSCs examined were higher than those in any of the fibroblasts. These results suggest that measuring the mRNA levels of IGF1 and SRGN before osteogenic induction will provide useful information for selecting competent MSCs for regenerative medicine, although the effectiveness of the markers is needed to be confirmed using a large number of MSCs, which have various levels of osteogenic differentiation potential.
Highlights
Mesenchymal stromal cells (MSCs) are multipotent precursor cells that differentiate into mature cells, such as osteocytes, adipocytes, chondrocytes, neurocytes, and cardiomyocytes [1,2,3]
Fleury, et al [23] found low, but significant, alkaline phosphatase (ALP) activity as an osteogenic differentiation marker after induction of fibroblasts. These findings suggest that osteogenic differentiation predictive markers can be identified by comparing osteogenic differentiation markers, such as ALP activity, with gene expression levels in fibroblasts and MSCs
To identify candidates for osteogenic differentiation predictive markers, we examined the correlation between gene expression levels before osteogenic induction of ilium MSCs and the extent of MSC differentiation after induction
Summary
Mesenchymal stromal cells (MSCs) are multipotent precursor cells that differentiate into mature cells, such as osteocytes, adipocytes, chondrocytes, neurocytes, and cardiomyocytes [1,2,3]. Previous studies have reported the use of MSCs in regenerative medicine and tissue engineering [4]; in particular, MSCs would be applicable to clinical practice for a wide range of bone diseases, such as fracture nonunion and periodontal bone loss [5,6,7]. MSCs obtained from different tissues have differing differentiation abilities. Bone marrow-derived MSCs exhibit a higher osteogenic differentiation potential than adipose-derived MSCs [8]. The adipogenic differentiation potential of adipose-derived MSCs is higher than that of bone marrow-derived MSCs, while MSCs derived from the synovium have a higher chondrogenic differentiation potential than bone marrow-derived MSCs [9]. MSCs obtained from different tissues seem to have intrinsic differentiation abilities related to their origin
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