Dataset Information

Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells.

ABSTRACT: Expansion in vitro prior to mesenchymal stem cells (MSCs) application is a necessary process. Functional and genomic stability has a crucial role in stem-cell-based therapies. However, the exact expression and co-expressed profiles of coding and non-coding RNAs in human bone marrow (BM)-MSCs in vitro aging are still lacking. In the present studies, the change of morphology, immunophenotype, and capacity of proliferation, differentiation, and immunoregulation of MSCs at passage (P) 4, P6, P8, P10, and P12 were investigated. RNA sequencing identified that 439 mRNAs, 65 long noncoding RNAs (lncRNAs), 59 microRNAs (miRNAs), and 229 circular RNAs (circRNAs) were differentially expressed (DE) in P12 compared with P4, with a similar trend in P6. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) identified several significant biological processes and pathways, including binding, ossification, and Wnt and PPAR signaling pathways. Interaction and co-expression/localization analyses were performed for DE mRNAs and lncRNAs, and several key lncRNAs, circRNAs, and important pathways like autophagy and mitophagy were identified in the competing endogenous RNA (ceRNA) network. Some key RNAs found in the bioinformatics analysis were validated. Our studies indicate that replicative senescence of MSCs is a continuous process, including widespread alterations in biological characteristics and global gene expression patterns that need to be considered before therapeutic applications of MSCs.

SUBMITTER: Wang S

PROVIDER: S-EPMC8479280 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells.

Wang Shan S Wang Ziming Z Su Hongjun H Chen Fenglei F Ma Mengjun M Yu Wenhui W Ye Guiwen G Cen Shuizhong S Mi Rujia R Wu Xiaohua X Deng Wen W Feng Pei P Zeng Chenying C Shen Huiyong H Wu Yanfeng Y

Molecular therapy. Nucleic acids 20210819

Expansion <i>in vitro</i> prior to mesenchymal stem cells (MSCs) application is a necessary process. Functional and genomic stability has a crucial role in stem-cell-based therapies. However, the exact expression and co-expressed profiles of coding and non-coding RNAs in human bone marrow (BM)-MSCs <i>in vitro</i> aging are still lacking. In the present studies, the change of morphology, immunophenotype, and capacity of proliferation, differentiation, and immunoregulation of MSCs at passage (P) ...[more]

PMID: 34631285

Similar Datasets

Project description:Mesenchymal stem cell (MSC) has great potential for both regenerative medicine and immunotherapy due to its multipotency and immunomodulatory property. The derivation of MSCs from human tissues involves an invasive procedure and the obtained MSCs often suffer from inconsistent quality. To overcome these issues, the approaches of deriving a highly potent and replenishable population of MSCs from human embryonic stem cells (hESCs) were established. However, few studies compared the immunological characteristics of MSCs derived from hESCs with tissue-derived MSCs or demonstrated differences and the underlying mechanisms. Here, we differentiated H9 hESCs into MSC-like cells (H9-MSCs) through an embryoid body outgrowth method and compared the immunological characteristics of H9-MSCs with bone marrow-derived MSCs (BMSCs). Both sources of derived cells exhibited typical MSC morphologies and surface marker expressions, as well as multipotency to differentiate into osteogenic and adipogenic lineages. A immunological characterization study showed that H9-MSCs and BMSCs had similar immunoprivileged properties without triggering allogeneic lymphocyte proliferation as well as equivalent immunosuppressive effects on T-cell proliferation induced by either cellular or mitogenic stimuli. Flow cytometry analysis revealed a lower expression of human major histocompatability complex class II molecule human lymphocyte antigen (HLA)-DR and a higher expression of coinhibitory molecule B7-H1 in H9-MSCs than in BMSCs. Interferon gamma (IFN-γ) is a proinflammatory cytokine that can induce the expression of HLA class II molecules in many cell types. Our results showed that pretreatment of H9-MSCs and BMSCs with IFN-γ did not change their immunogenicity and immunosuppressive abilities, but increased the difference between H9-MSCs and BMSCs for their expression of HLA-DR. Further detection of expression of molecules involved in IFN-γ signaling pathways suggested that the lower expression of HLA-DR in H9-MSCs could be partially attributed to the lower expression and the less nuclear translocation of its transcriptional factor CIITA. The present study provides evidence that the hESC-derived MSCs share similar immunogenicity and immunosuppressive abilities with BMSCs, but differ in the expression profile of immunological markers and the responsiveness to certain inflammatory cytokines, which suggests that H9-MSCs could be a safe and efficient candidate for MSC treatment in patients with inflammatory disorders.

Dataset Information

Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells.

Publications

Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets