Dataset Information

The Role of CDR1as in Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells.

ABSTRACT: Mesenchymal stem cells derived from human umbilical cord (hucMSCs) are considered a promising tool for regenerative medicine. circRNAs as newly discovered noncoding RNAs are involved in multiple biological processes. However, little has been known about the function of circRNAs in the proliferation and differentiation of hucMSCs. In this study, we selected several circRNAs expressed in MSCs from circBase and found that CDR1as expression level was markedly significant. We observed that, compared with that of uninduced hucMSCs, the CDR1as expression level of induced hucMSCs decreased with cell induction differentiation. By using siRNA to knock down CDR1as of hucMSCs, we discovered that proliferation was inhibited but the apoptosis increased. In addition, we found that the expression of stemness transcription factors (STFs) was downregulated after CDR1as knockdown and the adipogenesis and osteogenesis potential of hucMSCs was impaired. Our findings suggest that CDR1as takes a part in maintaining proliferation and differentiation of hucMSCs, providing clues for MSC modification and further for stem cell therapy and tissue regeneration.

SUBMITTER: Yang L

PROVIDER: S-EPMC6594288 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Role of CDR1as in Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells.

Yang Lunyu L Bin Zhang Z Hui Shi S Rong Li L You Benshuai B Wu Peipei P Han Xinye X Qian Hui H Xu Wenrong W

Stem cells international 20190612

Mesenchymal stem cells derived from human umbilical cord (hucMSCs) are considered a promising tool for regenerative medicine. circRNAs as newly discovered noncoding RNAs are involved in multiple biological processes. However, little has been known about the function of circRNAs in the proliferation and differentiation of hucMSCs. In this study, we selected several circRNAs expressed in MSCs from circBase and found that CDR1as expression level was markedly significant. We observed that, compared ...[more]

PMID: 31281369

Similar Datasets

Project description:Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are a novel and promising strategy for tissue engineering because of their ability to differentiate into many cell types. We characterized the differentiation of WJ-MSCs into endometrial epithelial cell (EEC)-like and endometrial stromal cell (ESC)-like cells and assessed the effect of 17?-estradiol and 8-Br-cAMP on the differentiation system.WJ-MSCs were treated in two ways to differentiate into EEC-like and ESC-like cells respectively: cocultured with ESCs in control/differentiation medium (17?-estradiol, growth factors); and cultured in control/differentiation medium (8-Br-cAMP alone or 8-Br-cAMP plus 17?-estrogen and growth factors). Three signaling pathway inhibitors (SB203580, PD98059, H89) were used to investigate the mechanism of WJ-MSC differentiation into ESC-like cells. Immunofluorescence, western blot and flow cytometry analyses were used to analyze expression of epithelial markers and stromal cell markers. Enzyme-linked immunosorbent assays were used to test the production of secretory proteins associated with the differentiation of ESC-like cells.17?-estradiol at 1 ?M downregulated vimentin and CD13 and upregulated cytokeratin and CD9 proteins, promoting the differentiation of WJ-MSCs into EEC-like cells in the coculture system. 8-Br-cAMP at 0.5 mM upregulated vimentin and CD13 and downregulated CK and CD9, promoting the differentiation of WJ-MSCs into ESC-like cells. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) were upregulated and the protein kinase A (PKA) signaling pathway was activated, whereas extracellular signal-regulated (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were not affected.17?-estradiol at 1 ?M is a good inducer for facilitating the differentiation of WJ-MSCs into EEC-like cells. 8-Br-cAMP plus estrogen and growth factors can induce the differentiation of WJ-MSCs into ESC-like cells. During the differentiation of WJ-MSCs into ESC-like cells, PRL and IGFBP1 were upregulated by the treatment and the PKA signaling pathway was activated, whereas ERK1/2 and p38 MAPK were not affected. These findings suggest a promising approach to the treatment of endometrial damage and other endometrial diseases and suggest new applications for WJ-MSCs in clinical practice.

Project description:Mesenchymal stem cells (MSCs) possess self-renewal and multipotential differentiation abilities, and they are thought to be one of the most reliable stem cell sources for a variety of cell therapies. Recently, cell therapy using MSCs has been studied as a novel therapeutic approach for cancers that show refractory progress and poor prognosis. MSCs from different tissues have different properties. However, the effect of different MSC properties on their application in anticancer therapies has not been thoroughly investigated. In this study, to characterize the anticancer therapeutic application of MSCs from different sources, we established two different kinds of human MSCs: umbilical cord blood-derived MSCs (UCB-MSCs) and adipose-tissue-derived MSCs (AT-MSCs). We used these MSCs in a coculture assay with primary glioblastoma multiforme (GBM) cells to analyze how MSCs from different sources can inhibit GBM growth. We found that UCB-MSCs inhibited GBM growth and caused apoptosis, but AT-MSCs promoted GBM growth. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling assay clearly demonstrated that UCB-MSCs promoted apoptosis of GBM via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL was expressed more highly by UCB-MSCs than by AT-MSCs. Higher mRNA expression levels of angiogenic factors (vascular endothelial growth factor, angiopoietin 1, platelet-derived growth factor, and insulin-like growth factor) and stromal-derived factor-1 (SDF-1/CXCL12) were observed in AT-MSCs, and highly vascularized tumors were developed when AT-MSCs and GBM were cotransplanted. Importantly, CXCL12 inhibited TRAIL activation of the apoptotic pathway in GBM, suggesting that AT-MSCs may support GBM development in vivo by at least two distinct mechanisms-promoting angiogenesis and inhibiting apoptosis. The opposite effects of AT-MSCs and UCB-MSCs on GBM clearly demonstrate that differences must be considered when choosing a stem cell source for safety in clinical application.

Dataset Information

The Role of CDR1as in Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells.

Publications

The Role of CDR1as in Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets