Project description:We enriched endothelial cells and other bone marrow cells in both fetal and adult stage to investigate Wnt signaling interaction using targeted scRNA-seq analysis. This analysis facilitate identification of sources of Wnt ligands and detection of Wnt receptor expression in bone marrow. The comparison of fetal and adult stage reveals differences of Wnt signaling in fetal and adult BM.
Project description:Background: Mesenchymal stromal cells (MSC) have been proposed as a future cell based therapy for lung diseases like bronchiolitis obliterans syndrome (BOS). Theoretically, it might be beneficial to use lung resident MSC already adapted to the pulmonary environment. We therefore aimed to compare lung MSC with the well-characterized bone marrow MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to MSC isolated from good outcome recipients. Methods: MSC were isolated from bone marrow (BM) and adult/fetal lung tissues and compared by a comprehensive panel of assays. Results:The gene expression profiles of adult lung derived and fetal lung derived MSC were very similar compared to BM derived MSC, with only 235 and 338 genes, respectively, being significantly differently expressed. Out of the 235 genes that were significantly different between adult lung derived and BM derived MSC, 90 genes were higher expressed in the lung derived MSC. In case of fetal lung derived MSC, 166 genes were higher expressed compared to the BM derived MSC. Interestingly, only, 89 genes were found to be expressed differently when comparing BM derived MSC to both, fetal and adult lung derived MSC, indicating that these genes are lung specific. Next, we went on to evaluate if MSC isolated from biopsies of lung-transplanted patients with BOS differed compared to patients without BOS, i.e. good outcome recipients. Here we found that four genes (Sox9, FAR2, LOC728855 and NDUFS5) were significantly higher expressed in MSC isolated from BOS patients Conclusions: This data demonstrates that lung resident MSC possess lung specific properties that should be taken into considerations when using MSC for cell-based therapy in severe lung disorders like BOS. These results also show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype. Comparison of gene expression of MSC isolated from bone marrow, adult lung and fetal lung.
Project description:Background: Mesenchymal stromal cells (MSC) have been proposed as a future cell based therapy for lung diseases like bronchiolitis obliterans syndrome (BOS). Theoretically, it might be beneficial to use lung resident MSC already adapted to the pulmonary environment. We therefore aimed to compare lung MSC with the well-characterized bone marrow MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to MSC isolated from good outcome recipients. Methods: MSC were isolated from bone marrow (BM) and adult/fetal lung tissues and compared by a comprehensive panel of assays. Results:The gene expression profiles of adult lung derived and fetal lung derived MSC were very similar compared to BM derived MSC, with only 235 and 338 genes, respectively, being significantly differently expressed. Out of the 235 genes that were significantly different between adult lung derived and BM derived MSC, 90 genes were higher expressed in the lung derived MSC. In case of fetal lung derived MSC, 166 genes were higher expressed compared to the BM derived MSC. Interestingly, only, 89 genes were found to be expressed differently when comparing BM derived MSC to both, fetal and adult lung derived MSC, indicating that these genes are lung specific. Next, we went on to evaluate if MSC isolated from biopsies of lung-transplanted patients with BOS differed compared to patients without BOS, i.e. good outcome recipients. Here we found that four genes (Sox9, FAR2, LOC728855 and NDUFS5) were significantly higher expressed in MSC isolated from BOS patients Conclusions: This data demonstrates that lung resident MSC possess lung specific properties that should be taken into considerations when using MSC for cell-based therapy in severe lung disorders like BOS. These results also show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype.
Project description:In animal models and human trials, intramyocardial injection of adult bone-marrow derived mesenchymal stem cells (BM-MSC) provides beneficial effects in failing hearts. These effects are mainly mediated through paracrine mechanisms. Mesenchymal stem cells of fetal origin (hAMC) can be isolated from the amniotic membrane of human placenta. Our results provide evidence that hAMC exert remarkable cardioprotective effects through paracrine mechanisms. However, the complete nature and scope of the paracrine mediators of cardioprotection have not been investigated yet. We compared the gene expression profiling of hAMC (n=8), BM-MSC (n=10) and dermal fibroblasts (n=6) to shed light onto the identity of putative cardioprotective factors secreted by fetal MSC.
Project description:In animal models and human trials, intramyocardial injection of adult bone-marrow derived mesenchymal stem cells (BM-MSC) provides beneficial effects in failing hearts. These effects are mainly mediated through paracrine mechanisms. Mesenchymal stem cells of fetal origin (hAMC) can be isolated from the amniotic membrane of human placenta. Our results provide evidence that hAMC exert remarkable cardioprotective effects through paracrine mechanisms. However, the complete nature and scope of the paracrine mediators of cardioprotection have not been investigated yet. We compared the gene expression profiling of hAMC (n=8), BM-MSC (n=10) and dermal fibroblasts (n=6) to shed light onto the identity of putative cardioprotective factors secreted by fetal MSC. Total RNA was extracted from cultured hAMC (n=8), BM-MSC (n=10) and dermal fibroblasts (n=6) and analyzed with HumanHT-12 v3 Expression BeadChips
Project description:Mesenchymal stromal cells (MSCs) are multipotent stem cells with potent immunosuppressive and trophic support functions. Although bone marrow is considered the golden standard to isolate classical MSCs (BM-MSC), MSC-like cells are currently also derived from other, more easily accessible extra-embryonic tissues such as the umbilical cord. In this study we compared the gene expression profile of human Wharton's jelly explant-derived MSC cultures with two adult MSC populations derived from bone marrow, namely BM-MSC and multipotent adult progenitor cells (MAPC). Here we demonstrate, by using genome wide gene expression analysis, that WJ-MSCs intrinsically have a differential gene expression profile compared to the adult MSCs. Gene ontology analysis revealed an increased expression of genes associated with cell-adhesion, proliferation, and immune system functioning. Furthermore, in comparison to adult MSC, stem cells from the Wharton’s jelly highly express genes involved in neurotrophic support (e.g. LIF, BDNF, NTF3). Such enhanced signatures make WJ-MSC an attractive candidate for cell-based therapy in neurodegenerative and immune-mediated CNS disorders such as multiple sclerosis or amyotrophic lateral sclerosis.
Project description:Expression analysis of migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow Keywords: fetal bone marrow, mesenchymal stromal cells, migration, gene expression, genomics Three biological replates for both migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow
Project description:Mesenchymal stromal cells (MSC) are ideal candidates for cell therapies, due to their immune-regulatory and regenerative properties. We have previously reported that lung-derived MSC are tissue-resident cells with lung-specific properties compared to bone marrow-derived MSC. Assessing relevant molecular differences between lung-MSC and bone marrow-MSC is important, given that such differences may impact their behavior and potential therapeutic use. Here, we present an in-depth mass spectrometry (MS) based strategy to investigate the proteomes of lung-MSC and bone marrow-MSC. The MS-strategy relies on label free quantitative data-independent acquisition (DIA) analysis and targeted data analysis using a MSC specific spectral library. We identified several significantly differentially expressed proteins between lung-MSC and bone marrow-MSC within the cell layer (352 proteins) and in the conditioned medium (49 proteins). Bioinformatics analysis revealed differences in regulation of cell proliferation, which was functionally confirmed by decreasing proliferation rate through Cytochrome P450 stimulation. Our study reveals important tissue-specific differences within proteome and matrisome profiles between lung- and bone marrow-derived MSC that may influence their behavior and affect the clinical outcome when used for cell-therapy.
Project description:Characterization of the transcriptional differences between human bone marrow MSC-derived cartilage, human neonatal, and adult cartilage