Integrated proteome and transcriptome analysis of serially passaged human umbilical cord mesenchymal stem cells to explore their maximal cell expansion boundary and bifurcation point
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ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Jing Liu
PROVIDER: PXD037211 | iProX | Sat Oct 08 00:00:00 BST 2022
REPOSITORIES: iProX
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Project description:Umbilical cord mesenchymal stem cells (UC-MSCs) have certain advantages over other MSCs and about 300 clinical trials have been registered using UC-MSCs to treat diseases such as osteoarthritis, autoimmune diseases, and degenerative disorders, yet, only limited success has been achieved. One reason is that in vitro expanded UC-MSCs show tremendous heterogeneity and their relationship to in vivo UC-MSCs remains unknown. Here, we investigated freshly isolated, uncultured UC-MSCs by single-cell RNA sequencing (scRNA-seq) and found two populations of UC-MSCs. Although UC-MSCs share many expressed genes and may have the same origin, they can be clearly separated based on differentially expressed genes including CD73 and other markers. Moreover, group 1 MSCs are enriched in expression of genes in immune response/regulatory activities, muscle cell proliferation and differentiation, stemness, and oxidative stress while group 2 MSCs are enriched with gene expression in extracellular matrix production, osteoblast and chondrocytes differentiation, and bone and cartilage growth. These findings suggest that UC-MSCs should be separated right after isolation and individually expanded in vitro to treat different diseases.
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Project description:Mesenchymal stem cells (MSCs) are highly important in biomedicine and hold great potential in clinical treatment for various diseases. In recent years, the capabilities of MSCs have been under extensive investigation for practical application. Regarding therapy, the efficacy usually depends on the amount of MSCs. Nevertheless, the yield of MSCs is still limited due to the traditional cultural methods. Herein, we proposed a three-dimensional (3D) scaffold prepared using poly lactic-co-glycolic acid (PLGA) nanofiber with polylysine (PLL) grafting, to promote the growth and proliferation of MSCs derived from the human umbilical cord (hUC-MSCs). We found that the inoculated hUC-MSCs adhered efficiently to the PLGA scaffold with good affinity, fast growth rate, and good multipotency. The harvested cells were ideally distributed on the scaffold and we were able to gain a larger yield than the traditional culturing methods under the same condition. Thus, our cell seeding with a 3D scaffold could serve as a promising strategy for cell proliferation in the large-scale production of MSCs. Moreover, the simplicity and low preparation cost allow this 3D scaffold to extend its potential application beyond cell culture.Graphical abstractSupplementary informationThe online version contains supplementary material available at 10.1186/s40643-023-00635-6.
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Project description:Active HUMSC with distinct binding rate to MDA MB-231 breast cancer cells, distinct ability in suppressing tumorigenesis,distinct cell in cell features and distinct features under TEM then inactive HUMSC We used microarrays to detail the difference gene expression between active HUMSC and inactive HUMSC HUMSC with high MDA MB-231 breast cancer cells suppression rate was selective as active HUMSC and HUMSC with low MDA MB-231 breast cancer cells suppression rate was selective as inactive HUMSC
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Project description:Although chorioamnionitis (CAM) has been demonstrated to be associated with numerous short- and long-term morbidities, the precise mechanisms remain unclear. One of the reasons for this is the lack of appropriate models for analyzing the relationship between the fetal environment and chorioamnionitis and fetal programming in humans. In this study, we aimed to clarify the fetal programming caused by CAM using the gene expression profiles of UCMSCs. From nine preterm neonates with CAM (n = 4) or without CAM (n = 5), we established UCMSCs. The gene expression profiles obtained by RNA-seq analysis revealed distinctive changes in the CAM group USMSCs. The UCMSCs in the CAM group had a myofibroblast-like phenotype with significantly increased expression levels of myofibroblast-related genes, including α-smooth muscle actin (p < 0.05). In the pathway analysis, the genes involved in DNA replication and G1 to S cell cycle control were remarkably decreased, suggesting that cellular proliferation was impaired, as confirmed by the cellular proliferation assay (p < 0.01-0.05). Pathway analysis revealed that genes related to white fat cell differentiation were significantly increased. Our results could explain the long-term outcomes of patients who were exposed to CAM and revealed that UCMSCs could be an in vitro model of fetal programming affected by CAM.
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Project description:Prior to (pre-) clinical application, MSC can be culture expanded as well as stimulated to activate their immunomodulatory properties. In the manuscript we show that stimulation of MSC induces immunophenotypical changes and marginally affects their DNA methylation pattern. Notably, culture expansion has a major impact on the DNA methylation profile of MSC, while their immunophenotype remained stable.
2018-04-24 | GSE113527 | GEO
Project description:Application of umbilical cord mesenchymal stem cell-derived conditioned media (HUCMSC-CM) to treat severe, progressive PAH. Serial infusions of HUCMSC-CM resulted in marked clinical and hemodynamic improvement after 6 months, and showed no adverse events. Differential expression analysis between conditioned media and cells was used to identify molecular processes with a putative role in treatment benefit.
2022-11-29 | PXD032234 | Pride
Project description:BackgroundMesenchymal stem cells (MSCs) have broad-spectrum therapeutic effects in various diseases, and thus have many clinical applications. However, it is difficult to produce sufficient numbers of MSCs for clinical use, and improved culture systems are required. Here, we report the effects of calcium (Ca2+) and hypoxia on the proliferation of human umbilical cord blood-derived MSCs (hUCB-MSCs). In addition, we determined the optimal conditions of these two factors for the large-scale culture of hUCB-MSCs.MethodshUCB-MSCs were maintained under hypoxic conditions (3% O2) with 1.8 mM Ca2+ during long-term culture, and their proliferation was evaluated. To characterize the underlying mechanisms, the effects on hypoxia-inducible factor (HIF)-1α and the extracellular signal-regulated kinase (ERK) signaling pathways were investigated. The therapeutic effects in a mouse emphysema model were analyzed and compared with those of naive MSCs.ResultsThe proliferation of Ca2+/hypoxia-treated hUCB-MSCs was increased compared with that observed using either calcium or hypoxia culture alone, without loss of stem cell marker expression or differentiation ability. The enhancement of the proliferation capacity of hUCB-MSCs by the synergistic effects of Ca2+ and hypoxia was dependent on the expression of HIF-1α and the ERK signaling pathway. The proliferation of Ca2+/hypoxia-treated hUCB-MSCs resulted in a delayed senescence phenotype and increased the expression levels of stemness genes such as Oct4 and Nanog compared to those observed in conventional culture conditions. In addition, Ca2+/hypoxia-treated MSCs transplantation in the mouse emphysema model showed the same therapeutic effects as observed with naive MSCs.ConclusionsThese findings suggest that a Ca2+/hypoxia-based expansion system has applications for the large-scale production of MSCs for therapeutic purposes.
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Project description:Uncovering the molecular mechanism of stem cell self-renewal is critical to broaden current therapeutic applications and to understand how its de-regulation may lead to pathological conditions. In this work, we report changes in gene expression and related cell processes during conditions of high in vitro expansion of CD133+/CD34+ primitive stem cells from human umbilical cord blood (UCB). Based on DNA microarray assays, we demonstrate that primary metabolism and cell cycle genes are specifically up-regulated, as well as members of the Wnt and Notch signaling pathways. Estradiol (E2) treatment resulted in enhanced cell expansion, which was correlated with activation of MEK/ERK signaling genes and inhibition of GLI2, a member of the Hedgehog pathway. Most notably, E2-induced CD133+/CD34+ cell expansion was highly associated to regulation of genes disrupted in cancer, such as the recently described DOCK4 and SPARCL1 tumor suppressor genes. Quantitative real-time PCR analysis confirmed down-regulation of DOCK4 and SPARCL1 in E2-treated CD133+/CD34+ cells and parallel results were verified when comparing their expression in mononuclear blood cells of chronic myeloid leukemia patients and healthy individuals. The striking differential expression of cancer-associated genes found reveals potential molecular targets for oncogenic transformation of CD133+/CD34+ cells and strengthens the importance of pre-clinical studies assessing safety of stem cell expansion protocols for therapeutic application. Keywords: dose response Gene expression intensities were measured using CodeLink Human Whole Genome Bioarrays.
2010-07-01 | E-GEOD-4609 | biostudies-arrayexpress
Project description:Ovarian injury because of chemotherapy can decrease the levels of sexual hormones and potentia generandi of patients, thereby greatly reducing quality of life. The goal of this study was to investigate which transplantation method for human umbilical cord mesenchymal stem cells (HUMSCs) can recover ovarian function that has been damaged by chemotherapy. A rat model of ovarian injury was established using an intraperitoneal injection of cyclophosphamide. Membrane-labelled HUMSCs were subsequently injected directly into ovary tissue or tail vein. The distribution of fluorescently labelled HUMSCs, estrous cycle, sexual hormone levels, and potentia generandi of treated and control rats were then examined. HUMSCs injected into the ovary only distributed to the ovary and uterus, while HUMSCs injected via tail vein were detected in the ovary, uterus, kidney, liver and lung. The estrous cycle, levels of sex hormones and potentia generandi of the treated rats were also recovered to a certain degree. Moreover, in some transplanted rats, fertility was restored and their offspring developed normally. While ovary injection could recover ovarian function faster, both methods produced similar results in the later stages of observation. Therefore, our results suggest that transplantation of HUMSCs by tail vein injection represents a minimally invasive and effective treatment method for ovarian injury.
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Project description:ObjectiveUmbilical cord blood (UCB) is an accessible and effective alternative source for hematopoietic stem cell (HSC) transplantation. Although the clinical application of UCB transplantation has been increased recently, quantitative limitation of HSCs within a single cord blood unit still remains a major hurdle for UCB transplantation. In this study we used microcarrier beads to evaluate the ex vivo expansion of UCB-derived HSCs in co-cultured with UCB-derived mesenchymal stem cells (MSC).Materials and methodsIn this experimental study, we used microcarrier beads to expand UCB-derived MSCs. We investigated the simultaneous co-culture of UCB-derived CD34+ cells and MSCs with microcarrier beads to expand CD34+ cells. The colony forming capacity and stemness-related gene expression on the expanded CD34+ cells were assessed to determine the multipotency and self-renewal of expanded cells.ResultsOur results indicated that the microcarrier-based culture significantly increased the total number and viability of UCB-derived MSCs in comparison with the monolayer cultures during seven days. There was a significant increase in the UCB-derived CD34+ cells expanded in the presence of microcarrier beads in this co-culture system. The expanded UCB-derived CD34+ cells had improved clonogenic capacity, as evidenced by higher numbers of total colony counts, granulocyte, erythrocyte, monocyte, megakaryocyte colony forming units (CFU-GEMM), and granulocyte-monocyte colony forming units (CFU-GM). There were significantly increased expression levels of key regulatory genes (CXCR4, HOXB4, BMI1) during CD34+ cells self-renewal and quiescence in the microcarrier-based co-culture.ConclusionOur results showed that the increase in the expansion and multipotency of CD34+ cells in the microcarrierbased co-culture can be attributed to the enhanced hematopoietic support of UCB-derived MSCs and improved cell-cell interactions. It seems that this co-culture system could have the potential to expand primitive CD34+ cells.
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