Comparison of human isogeneic Wharton’s Jelly MSCs and iPSC-derived MSCs responses to interferon-gamma (IFNG) stimulation
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PROVIDER: PRJNA543998 | ENA |
REPOSITORIES: ENA
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Project description:To explore differences between native MSCs (nMSCs) and iPSC-derived MSCs (iMSCs), we developed isogeneic lines from Wharton’s Jelly (WJ) from the umbilical cords of two donors (#12 and #13) under xeno-free conditions. Next, we reprogrammed them into iPSCs (iPSC12 and iPSC13) and subsequently differentiated them back into iMSCs (iMSC12 and iMSC13) using two different protocols, which we named ARG and TEX. As an additional control, we used human embryonic stem cell line KCL034 to differentiate the cells into eMSC following ARG and TEX protocols. We assessed IFNG-induced changes in all lines. Our data suggest that, following a careful selection and screening of donors, nMSCs from umbilical’s cord WJ can be easily reprogrammed into iPSCs providing an unlimited source of material for differentiation into iMSCs. However, the differentiation protocol should be chosen depending on their clinical use.
2020-03-23 | GSE131499 | GEO
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Project description:Wharton’s jelly derived Mesenchymal Stem Cells (MSCs) isolated from newborns with intrauterine fetal growth restriction were previously shown to exert anabolic features including insulin hypersensitivity. Here, we extend these observations and demonstrate that MSCs from small for gestational age (SGA) individuals have decreased mitochondrial oxygen consumption rates. Comparing normally grown and SGA MSCs using next generation sequencing studies, we measured global transcriptomic and epigenetic profiles and identified in SGA, E2F1 as an over-expressed transcription factor regulating oxidative metabolism. We further show that E2F1 regulates the differential transcriptome found in SGA and is associated with the activating histone marks H3K27ac and H3K4me3. One of the key genes regulated by E2F1 was found to be the fatty acid elongase ELOVL2, a gene involved in the endogenous synthesis of docosahexaenoic acid (DHA).
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Project description:Transcriptome analysis of human Wharton’s jelly stem cells
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Project description:Mesenchymal stem cell (MSC) transplantation is a promising therapy for regenerative medicine. However, MSCs cultured in two-dimensional (2D) culture conditions are significantly different from the cell shape in the body, down-regulation of stemness genes and the secretion of paracrine factors. Here, we evaluated the effect of 3D culture using Cellhesion VP, a water-insoluble material composing of chitin-based polysaccharide fibers, on the characteristics of human Wharton’s jelly-derived MSCs (hWJ-MSCs). Cellhesion VP significantly increased the cell proliferation after retrieval. Transcriptome analysis revealed that genes involved in cell stemness, migration ability, and extracellular vesicle (EV) production appeared to be enhanced by 3D culture. Subsequent biochemical analyses showed that the expression levels of stemness genes including OCT4, NANOG, and SSEA4 were up-regulated, and migration capacity was elevated in 3D cultured hWJ-MSCs. In addition, the EV production was significantly increased in 3D cells, which contained a distinct protein profile from 2D cells. Gene and drug connectivity analysis revealed that the 2D and 3D EVs had similar functions as immunomodulators; however, 3D EVs had completely distinct therapeutic profiles on various infectious and metabolic diseases by activating the disease-associated signaling pathways. Therefore, EVs from Cellhesion VP-primed hWJ-MSCs appear as a new treatment for immune and metabolic diseases.
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Project description:Human mesenchymal stem cells (hMSCs) have therapeutic applications and potential for use in regenerative medicine. However, the use of hMSCs in research and clinical medicine is limited by a lack of information pertaining to their donor-specific functional attributes. In this study, we compared the characteristics of same-donor derived placenta (PL) and Wharton’s jelly (WJ)-derived hMSCs, we also compared their mechanism of action in a skeletal muscle disease in vitro model. The effects of GRO-α were also investigated in a Duchenne muscular dystrophy (DMD) mouse model. The same-donor-derived hWJ- and hPL-MSCs exhibited typical hMSC characteristics. GRO-α was differentially expressed in hWJ- and hPL-MSCs. However, when the secretion of GRO-α was considered, hWJ-MSCs displayed a higher ability to inhibit necroptosis in skeletal muscle cells than hPL-MSCs. This demonstrates the anti-necroptotic therapeutic effect of GRO-α in the skeletal muscle cell death model. Furthermore, considering their potential to inhibit necroptosis in skeletal muscle cells, hWJ-MSCs and the derived GRO-α are novel treatment options for skeletal muscle diseases such as DMD.
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Project description:Mesenchymal stem cells (MSCs) are generally considered the main tool box for cell-based therapies and compared to embryonic stem cells (ESCs), MSCs exhibit many advantages. It has been shown that UC matrix (the Wharton’s Jelly surrounding umbilical vessels) contains a great number of mesenchymal cells. The abundant amount of Wharton’s Jelly (WJ) makes it an attractive source of MSCs for cell-based therapies. recently have been highlighted the changes in protein expression profiling during in vitro expansion of WJ-MSC, probably related to the gradual reduction of their staminal plasticity and to the biological cellular mechanism occurring in the cellular aging. The aim of the present work was to analyze the transcriptomic profile useful to the definition of WJ-MSC characteristics and therefore identify possible different new marker candidates. In these contest, changes in gene expression profiles occurring during WJ-MSC in vitro growth wile by analyzed in order to find possible modulation related to their long expansion and fast growth abilities. We analyzed the changes in total RNA expression at the 12th in vitro expansion cycle compared to the 4th in vitro expansion cycle.
2012-06-28 | GSE34929 | GEO
Project description:Variability among donors, non-standardized methods for isolation, and characterization contribute to mesenchymal stem/stromal cell (MSC) heterogeneity. Induced pluripotent stem cell (iPSCs)-derived MSCs would circumvent many of current issues and enable large-scale production of standardized cellular therapy. To explore differences between native MSCs (nMSCs) and iPSC-derived MSCs (iMSCs), we developed isogeneic lines from Wharton's jelly (WJ) from the umbilical cords of two donors (#12 and #13) under xeno-free conditions. Next, we reprogrammed them into iPSCs (iPSC12 and iPSC13) and subsequently differentiated them back into iMSCs (iMSC12 and iMSC13) using two different protocols, which we named ARG and TEX. We assessed their differentiation capability, transcriptome, immunomodulatory potential, and interferon-γ (IFNG)-induced changes in metabolome. Our data demonstrated that although both differentiation protocols yield iMSCs similar to their parental nMSCs, there are substantial differences. The ARG protocol resulted in iMSCs with a strong immunomodulatory potential and lower plasticity and proliferation rate, whereas the TEX protocol raised iMSCs with a higher proliferation rate, better differentiation potential, though weak immunomodulatory response. Our data suggest that, following a careful selection and screening of donors, nMSCs from umbilical's cord WJ can be easily reprogrammed into iPSCs, providing an unlimited source of material for differentiation into iMSCs. However, the differentiation protocol should be chosen depending on their clinical use.
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Project description:Human Wharton’s jelly stem cells (hWJSCs) are multipotent stem cells extensively employed in biotechnology applications and can be differentiated into distinct lineages through various culture approaches. However, the impact of simulated microgravity (sμG) on the growth, differentiation, and viability of this cell population is incompletely characterized. We aimed to determine whether acute (72 hour) exposure to lunar sμG (0.16 G) elicited changes in growth, viability and lineage differentiation in hWJSCs and if putative changes were maintained once exposure to terrestrial gravity (1.0G) was restored. Our data support earlier findings that acute sμG significantly reduces cell division potential of hWJSCs, and suggest that actute sμG-exposure induces reversible changes in cell growth accompanied by osteocyte – chondrocyte changes in lineage differentiation.
2024-05-09 | GSE248366 | GEO
Project description:Human Wharton’s jelly stem cells (hWJSCs) are derived ethically in large amounts from the umbilical cord matrix. Besides their differentiation capabilities, WJSCs also display a notable lack of ability to form teratoma. hWJSCs have been shown to exert immunomodulatory effects and have recently been reported to kill or diminish cancer cell growth. These characteristics are important considerations for their use in cell therapy. In this transcriptome analysis, hWJSCs were profiled using Affymetrix DNA microarrays and compared to a panel of human stem cells and stromal cells. Although hWJSCs are multipotent, they expressed very low levels of the majority of stem cell markers, including POU5F1, NANOG, SOX2 and LIN28. BIRC5 has recently been shown to be required for teratoma formation in SCID mice. The lower levels of BIRC5 expression in hWJSCs compared to hESCs and the very low levels of stem cell markers might account for hWJSCs inability to form teratomas. IL12A which is known to be associated with the induction of apoptosis, was amongst the several cytokines identified to be significantly upregulated in hWJSCs. The ability of hWJSCs to compliment the host immune responses was further highlighted with the GO Biological Process analysis showing high association with immune system, chemotaxis and cell death. The ability to modulate immune responses confers hWJSCs an additional advantage in stem cell therapy and potentially allows hWJSCs as a form of treatment for cancer and immune disorders. In summary, the transcriptome profile of hWJSCs has provided indications on the genetic basis for their biological characteristics in immunomodulatory response, anti-cancer effects, and the lack of teratoma formation. This SuperSeries is composed of the SubSeries listed below.
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