Expression data from type 2 diabetes mellitus adipose-derived stem cells cultured with basic fibroblast growth factor
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE283040 | GEO | 2025/08/27
REPOSITORIES: GEO
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Project description:The treatment of bone defects caused by infection, trauma or neoplasms remains a clinical challenge. Autologous bone transplantation is limited by availability, donor site morbidity and surgical risk factors. This has given rise to stromal/stem-cell based therapy. Bone marrow derived stromal cells (BMSCs) have been studied to a large extent and show high regenerative potential but their use is limited by availability, donor site morbidity and the relatively low cell yield as they represent only <0.1% of cell harvested from bone marrow aspirate. At the same time, they are the closest mesenchymal stromal cells for bone tissue engineering given their tissue origin and, unlike other mesenchymal stromal cells, can support the formation of hematopoietic marrow. Adipose tissue derived stromal cells (ASCs) as part of the stromal vascular fraction of adipose tissue can as well undergo osteogenic differentiation but can be additionally isolated in a sufficient quantity from lipoaspirate after liposuction of abundant subcutaneous fat tissue. Here, it has been shown that there are no major differences in regard to proliferation or differentiation capacity of ASCs derived from subcutaneous fat of different anatomical regions. It has been shown that BMSCs are more prone to senescence during expansion and passage than ASCs and that ageing impacts proliferative capabilities of BMSCs more than that of ASCs while it has also been reported that osteogenic differentiation capacity is least impacted by age. Multiple studies have compared the characteristics of these two mesenchymal stromal cells in regard to bone tissue engineering in vitro. Most studies point to inferior extracellular matrix mineralization and lower expression of key osteogenic transcription markers like Runx2 in osteogenic differentiated ASCs compared to BMSCs. On the other hand, a study by Rath et al. found contrary results using particular culturing conditions like 3D bioglass scaffolds. An intraindividual comparison of human MSCs of three donors cultured on decellularized porcine bone confirmed superior osteogenic capacity of BMSCs compared to ASCs. In contrast to BMSCs, ASCs were not able to induce heterogenic ossification in a mouse model. In a sheep tibia defect model application of BMSCs resulted in a significantly higher amount of newly formed bone tissue. Importantly, Osteogenic differentiated ASCs do not support the formation of a hematopoietic marrow. Proteomics enables large-scale analysis of proteins present in a cell type and can be used to identify differentially regulated key proteins in a comparative approach. A comparative proteomic analysis of BMSCs and ASCs by Roche et al. in 2009 identified 556 proteins with 78% of these not being differentially regulated between these two cell populations, regarded as high similarity. Another comparative proteomic study of 2016 by Jeon et al. found 90 differentially regulated proteins out of 3000 total identified proteins. Both studies do not specify a number of different tissue donors and in part using cell lines. Looking for differences upon osteogenic differentiation, transcriptomic comparison of osteogenic differentiated porcine ASCs and BMSCs has been performed, resulting in 21 differentially expressed genes after 21 days of osteogenic culture conditions. Still, it remains unanswered, which are the key distinctive features of osteogenic differentiated ASCs and BMSCs at protein level that might help address the abovementioned weaknesses of ASCs in bone tissue engineering/regeneration for translational research. To overcome this need, an intraindividual comparative DIA based proteomic analysis of osteogenic differentiated human BMSC and ASCs was performed in this study.
2021-06-09 | PXD015223 | Pride
Project description:A major challenge in realizing regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs) is the cellular heterogeneity and donor variability. Ex vivo expanded ADRCs (=ASCs) are available at larger quantities and represent a more homogeneous population suitable for allogenic use. Emerging pre-clinical and clinical data however suggest similar, or even superior efficacy of ADRCs as compared to ASCs for indications involving (micro)vascular deficiency. Since CD31+ ADRCs lack in cultured ASCs, we hypothesized that these cells account for improvement of vascular function in the heterogenous ADRCs. Herein, we found that in patients with erectile dysfunction (ED), the number of injected CD31+ ADRCs correlates positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31- and parent ADRCs. CD31+, CD31- and ADRCs were co-cultured in aortic ring-, as well as in ED-relevant corpus cavernousum tube formation assays, both showing a significantly higher ability of the CD31+ ADRCs to support tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is explained by secretory pro-angiogenic proteins such as DKK3, ANGPT2, ANAX2 and VIM, all being enriched in CD31+ADRC CM. To gain further specification of the ADRC subpopulations expressing these proteins, single-cell RNA sequencing was performed and showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data thus suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs, which likely represent an improved alternative to heterogenous ADRCs as well as ASCs when aiming for vascular repair in cell therapy.
2023-10-24 | PXD040388 | Pride
Project description:Disordered angiogenesis is implicated in the pulmonary vascular remodeling secondary to congenital heart disease (CHD). However, the underlying genes are not well delineated. We have previously shown that an ovine model of CHD with increased pulmonary blood flow (PBF, Shunt) has an M-bM-^@M-^\angiogenesis burstM-bM-^@M-^] between 1-4 weeks of age. Thus, we hypothesized that the increased pulmonary blood flow elicited a pro-angiogenic gene expression profile prior to the onset of vessel growth. To test this we utilized microarray analysis to identify genes that could be responsible for the angiogenic response. Total RNA was isolated from the lungs of Shunt and Control lambs at 3 days of age and hybridized to Affymetrix GeneChips for microarray analyses (n=8 for each group). A total of 89 angiogenesis-related genes were found to be up-regulated and 26 angiogenesis-related genes down-regulated in Shunt lungs compared to control (cutting at 1.2 fold difference, P<0.05). We then confirmed the up-regulation of pro-angiogenic genes: FGF2, Angiopoietin2 (Angpt2), and Birc5 at both mRNA and protein levels and the up-regulation of ccl2 at mRNA level in the 3-day shunt lungs. Further, we found that pulmonary arterial endothelial cells (PAEC) isolated from juvenile lambs exhibited increased expression of FGF2, Angpt2, Birc5, and ccl2 as well as enhanced angiogenesis when exposed to elevated shear stress (35 dyn/cm2) compared to cells exposed to more physiological level shear stress (20 dyn/cm2). Finally, we demonstrated that blocking FGF2, Angpt2, or Birc 5 signaling, using neutralizing antibodies, significantly decreased the angiogenic response induced by shear stress. In conclusion, we have identified a pro-angiogenic gene expression profile in a lamb model of CHD with increased PBF that precedes the onset of pulmonary vascular remodeling. Further, our data indicate that FGF2, Angiopoietin2, Birc5, and ccl2 may play important roles in the angiogenic response. Total RNA was isolated from the lungs of Shunt and Control lambs at 3 days of age and hybridized to Affymetrix GeneChips for microarray analyses. Eight chips were employed for both control and shunt groups.
2011-03-10 | E-GEOD-22590 | biostudies-arrayexpress
Project description:Disordered angiogenesis is implicated in the pulmonary vascular remodeling secondary to congenital heart disease (CHD). However, the underlying genes are not well delineated. We have previously shown that an ovine model of CHD with increased pulmonary blood flow (PBF, Shunt) has an “angiogenesis burst” between 1-4 weeks of age. Thus, we hypothesized that the increased pulmonary blood flow elicited a pro-angiogenic gene expression profile prior to the onset of vessel growth. To test this we utilized microarray analysis to identify genes that could be responsible for the angiogenic response. Total RNA was isolated from the lungs of Shunt and Control lambs at 3 days of age and hybridized to Affymetrix GeneChips for microarray analyses (n=8 for each group). A total of 89 angiogenesis-related genes were found to be up-regulated and 26 angiogenesis-related genes down-regulated in Shunt lungs compared to control (cutting at 1.2 fold difference, P<0.05). We then confirmed the up-regulation of pro-angiogenic genes: FGF2, Angiopoietin2 (Angpt2), and Birc5 at both mRNA and protein levels and the up-regulation of ccl2 at mRNA level in the 3-day shunt lungs. Further, we found that pulmonary arterial endothelial cells (PAEC) isolated from juvenile lambs exhibited increased expression of FGF2, Angpt2, Birc5, and ccl2 as well as enhanced angiogenesis when exposed to elevated shear stress (35 dyn/cm2) compared to cells exposed to more physiological level shear stress (20 dyn/cm2). Finally, we demonstrated that blocking FGF2, Angpt2, or Birc 5 signaling, using neutralizing antibodies, significantly decreased the angiogenic response induced by shear stress. In conclusion, we have identified a pro-angiogenic gene expression profile in a lamb model of CHD with increased PBF that precedes the onset of pulmonary vascular remodeling. Further, our data indicate that FGF2, Angiopoietin2, Birc5, and ccl2 may play important roles in the angiogenic response.
2011-03-10 | GSE22590 | GEO
Project description:We previously reported that a vascular endothelial stem cell population resides in pre-existing blood vessels in mice and may contribute to vascular endothelial cells in liver injury or hind limb ischemia models in the long-term. However, whether such stem cells exist in humans and can differentiate specifically into vascular endothelial cells have not been determined. We hypothesized that CD157+ vascular endothelial cells in humans may also possess high angiogenic potential. First, human-derived induced pluripotent stem cells were differentiated into vascular endothelial cells, and the expression of CD157 was monitored during the differentiation process. We found that CD157 emerged 11 days after the induction of differentiation, peaked at 14 days, and then declined by 24 days. WNext, we also evaluated blood vessel formation by 14- and 24-day-old vascular endothelial cells.It was found that 14-day-old cells, when CD157 expression was at its peak, formed more blood vessels than 24-day-old cells.These results suggest that vascular endothelial cells expressing CD157 have high angiogenic potential and may exist as vascular endothelial stem cells.
2025-06-01 | GSE287034 | GEO
Project description:We isolated adipose-derived mesenchymal stem cells (ASCs) from the lymphedema adipose tissue from liposuction specimens of 10 patients with malignancy-related extremity lymphedema, and we used adipose tissue from the normal upper abdomen of the same patients as control tissue. We compared the proliferation and adipogenic differentiation capacity between the two kinds of ASCs, and we explored the transcriptomic differences between them. We found that lymphedema-associated ASCs had more rapid proliferation and a higher adipogenic differentiation capacity. CDK1 inhibitors could return the abnormal biological characteristics of these cells to normal phenotype, suggesting that CDK1 is a key driver of proliferation and adipogenic differentiation in these cells, which might expound the accumulation of adipose tissue extensively observed in secondary lymphedema, indicating the CDK1 may be a potential target for lymphedema therapy. On the other hand, our finding showed that ASCs from lymphedema adipose tissues have higher immunosuppressive effect, and the inhibition of up-regulated cytokine CHI3L1 may be clinically beneficial. In summary, explore the underlying mechanisms of fat deposition in lymphedema may provide powerful strategies for the treatment of lymphedema.
2019-06-19 | GSE132936 | GEO
Project description:WNT2 is important for placenta vascularization and acts as a pro-angiogenic factor for liver and other endothelial cells (ECs). WNT2 induction has been shown in many carcinomas and is associated with tumor progression. In colorectal cancer (CRC) WNT2 is selectively elevated in cancer associated fibroblasts (CAFs), leading to increased invasion and metastasis. However, if there is a role for WNT2 in colon cancer angiogenesis has not been addressed so far. Here, we demonstrate that WNT2 enhances EC migration and invasion, while it induces ß catenin dependent signaling in only a small subset of HUVECs. We show that siRNA-mediated knockdown of WNT2 in CAFs reduced the growth of vessel-like structures significantly in a co-culture assay, while the overexpression of WNT2 in skin fibroblasts otherwise being devoid of WNT2 led to increased angiogenesis in vitro. In a xenograft model, overexpression of WNT2 in HCT116 led to enhanced tumor volume and vessel density. Moreover, WNT2 expression correlates with vessel markers in human CRC. Secretome profiling of CAFs revealed that proteins related to angiogenesis and extracellular matrix (ECM) remodeling are regulated by WNT2. Thus, stroma-derived WNT2 positively affects angiogenesis in CRC by shifting the balance towards pro-angiogenic signals.
2020-05-26 | PXD014019 | Pride
Project description:Circulating osteoprogenitor (COP) are a population of cell in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). While there is functional overlap, it is not known how COP cells are related to bone marrow (BM)-derived MSCs (BM-MSCs) and other better characterized stromal progenitor populations such as adipose-derived stromal cells (ASCs). This study compares COP cells to BM-MSCs and ASCs through detailed transcriptomic and proteomic analyses. COP cells have a distinct gene and protein expression pattern to BM-MSCs and ASCs, with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. However, they also have a similar pattern of expression BM-MSCs and ASCs, in genes and proteins in progenitor cell differentiation and proliferation pathways. This study shows COP cells to be a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, but with a strong immune phenotype, with potential for translational regenerative medicine strategies.
2024-10-17 | PXD035803 | Pride
Project description:Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes. The aim of this study was to investigate the effect of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from mice fed a high-fat sucrose (HFS) diet exhibited reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than those from the control group (C). The results showed that ASCs from mice fed the HFS diet had reduced adipogenic capacity. Mitochondrial analysis showed increased mitochondrial activity in undifferentiated ASC-HFS, but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 acetylation profile of ASCs in genes related to adipogenesis, mitochondrial function, inflammatory response and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations in genes related to inflammatory response and immunomodulation. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. This study demonstrates that HFS diet induces profound epigenetic and transcriptomic changes in ASCs, leading to impaired differentiation and dysfunctional adipocyte formation.
2024-06-06 | GSE255334 | GEO
Project description:Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes. The aim of this study was to investigate the effect of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from mice fed a high-fat sucrose (HFS) diet exhibited reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than those from the control group (C). The results showed that ASCs from mice fed the HFS diet had reduced adipogenic capacity. Mitochondrial analysis showed increased mitochondrial activity in undifferentiated ASC-HFS, but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 acetylation profile of ASCs in genes related to adipogenesis, mitochondrial function, inflammatory response and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations in genes related to inflammatory response and immunomodulation. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. This study demonstrates that HFS diet induces profound epigenetic and transcriptomic changes in ASCs, leading to impaired differentiation and dysfunctional adipocyte formation.
2024-06-06 | GSE255335 | GEO