Collagen Modulates the Biological Characteristics of WJ-MSCs in Basal and Osteoinduced Conditions

Abstract

Transcriptomic analysis revealed mesenchymal stem/stromal cells (MSCs) from various origins exhibited distinct gene and protein expression profiles dictating their biological properties. Although collagen type 1 (COL) has been widely studied in bone marrow MSCs, its role in regulating cell fate of Wharton jelly- (WJ-) MSCs is not well understood. In this study, we investigated the effects of collagen on the characteristics of WJ-MSCs associated with proliferation, surface markers, adhesion, migration, self-renewal, and differentiation capabilities through gene expression studies. The isolated WJ-MSCs expressed positive surface markers but not negative markers. Gene expression profiles showed that COL not only maintained the pluripotency, self-renewal, and immunophenotype of WJ-MSCs but also primed cells toward lineage differentiations by upregulating BMP2 and TGFB1 genes. Upon osteoinduction, WJ-MSC-COL underwent osteogenesis by switching on the transcription of BMP6/7 and TGFB3 followed by activation of downstream target genes such as INS, IGF1, RUNX2, and VEGFR2 through p38 signalling. This molecular event was also accompanied by hypomethylation at the OCT4 promoter and increase of H3K9 acetylation. In conclusion, COL provides a conducive cellular environment in priming WJ-MSCs that undergo a lineage specification upon receiving an appropriate signal from extrinsic factor. These findings would contribute to better control of fate determination of MSCs for therapeutic applications related to bone disease.

The Molecular Regulatory Mechanism in Multipotency and Differentiation of Wharton’s Jelly Stem Cells

“…IGFBP2 promotes adipogenic differentiation of WJ-MSCs by increasing the phosphorylation of JNK/AKT and activating the JNK/AKT signaling pathway [ 98 ]. COL induces osteogenic differentiation by activating the transcription of BMP6/7 and TGFB3, and then activating the downstream target genes INS , IGF1 , RUNX2 and VEGFR2 through the p38/MAPK pathway [ 99 ]. After BMP receptors are activated, phosphorylated TAK1 recruits TAB1 to initiate MKK-p38 MAPK or MKK-ERK1/2 signaling ( Figure 4 ).…”

“…Intriguingly, the differentiation of WJ-MSCs into osteoblasts involves different genetic/epigenetic regulatory mechanisms that work together to promote WJ-MSCs to differentiate into osteoblasts. For instance, RUNX2, a downstream target gene of the p38/MAPK signaling pathway [ 99 ], is also an important regulator of osteogenic differentiation. When JARID1B is enriched in the P1 promoter region of RUNX2 , the levels of activation marks, including histone H3ac and H3K4me3, are reduced, whereas increased levels of the suppressive mark histone H3K27me3 lead to the inhibition of RUNX2 transcription [ 34 ].…”

Self-assembly of three-dimensional liver organoids: virtual reconstruction via endocytosed polymer dots for refactoring the fine structure

“…Subsequently, the base of the culture dish was adorned with Wharton's Jelly, serving as the culture substrate of the cell mass, to mimic the growth microenvironment of the MSCs and minimize the adhesion between the cells and the culture dish. 18 Finally, MHs cultured for 18 days served as the principal cellular constituent, combined with MSCs and HUVECs in a predetermined ratio (MHs : MSCs : HUVECs—5 : 1 : 4), and the cells were seeded under 2D conditions. Owing to their intrinsic organizational capabilities, the cell clusters self-assembled into visibly discernible 3D cell clusters within approximately three days post-seeding.…”