Mesenchymal stem cells in local fat depots stimulate breast cancer growth, invasion and desmoplasia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE24433 | GEO | 2011/08/01
SECONDARY ACCESSION(S): PRJNA132785
REPOSITORIES: GEO
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Project description:Studies investigating the role of mesenchymal stem cells (MSCs) in mammary carcinogenesis have almost exclusively relied on isolates from bone marrow aspirates or non-breast fat sources often making the general assumption that all MSCs are alike. Here we conduct the first extensive analysis of human breast adipose MSCs to define similarities and differences to MSCs isolated from non-breast sources (subcutaneous abdominal tissue) and bone marrow.
2011-07-31 | E-GEOD-24433 | biostudies-arrayexpress
Project description:Studies investigating the role of mesenchymal stem cells (MSCs) in mammary carcinogenesis have almost exclusively relied on isolates from bone marrow aspirates or non-breast fat sources often making the general assumption that all MSCs are alike. Here we conduct the first extensive analysis of human breast adipose MSCs to define similarities and differences to MSCs isolated from non-breast sources (subcutaneous abdominal tissue) and bone marrow.
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Project description:Expression profiling of lung derived mesenchymal stromal cells to lung fibrblasts and cord blood derived mesenchymal stromal cells We have previously isolated mesenchymal stromal cells (MSCs) from the tracheal aspirates of premature neonates with respiratory distress. While isolation of MSCs correlates with the development of bronchopulmonary dysplasia, the physiologic role of these cells remains unclear. To address this, we further characterized the cells, focusing on the issues of gene expression, origin and cytokine expression. Microarray comparison of early passage neonatal lung MSC gene expression to cord blood MSCs and human fetal and neonatal lung fibroblast lines demonstrated that the neonatal lung MSCs differentially expressed 971 gene probes compared to cord blood MSCs, including the transcription factors Tbx2, Tbx3, Wnt5a, FoxF1 and Gli2, each of which have been associated with lung development. Compared to lung fibroblasts, 710 gene probe transcripts were differentially expressed by the lung MSCs, including IL-6 and IL-8/CXCL8. Further, neonatal lung MSCs exhibited a pattern of Hox gene expression distinct from cord-blood MSCs but similar to human fetal lung fibroblasts, consistent with a lung origin. Together, these data suggest that MSCs isolated from neonatal tracheal aspirates originate in the lung and are distinct from lung fibroblasts.
2010-10-08 | E-GEOD-24583 | biostudies-arrayexpress
Project description:Aims Mesenchymal stromal cells (MSCs) are being tested and accepted as a source for cell therapy worldwide. However, the advanced age of the patients, together with the difficulties in achieving the required cell amounts, impede autologous treatments. Reprogramming of MSCs into induced pluripotent stem cells (iPSCs), followed by re-differentiation to MSCs has emerged as a promising and safe method to facilitate the cell expansion and the removal of aging-associated characteristics. However, the effect of reprogramming on the MSC’s pro-angiogenicity is poorly understood. Materials and Methods In this study, we use a microfluidic organ-on-a-chip platform designed for vascularization assays to study and compare the effects of bone marrow MSCs (BM-MSCs) and iPSC-derived MSCs (iMSCs) in stimulating the formation of vessels by endothelial cells. Cells were loaded in fibrin hydrogels, injected into the microfluidic channel, and grown for ten days. Key findings Fluorescence microscopy revealed that BM-MSCs promote the formation of long and interconnected endothelial vessels, while iMSCs barely stimulate neoangiogenesis. This was further confirmed and explained by bulk RNA sequencing, showing a decrease of pro-angiogenic agents in both of the iMSCs co-cultures. Furthermore, transmission electron microscopy revealed that BM-MSCs closely associate with the new vessels as perivascular cells, while iMSCs just remain in proximity. Significance These results highlight iMSCs as a promising substitute for BM-MSCs in the treatment of diseases with pernicious vascularization, such as osteoarthritis, ocular degeneration, and cancer.
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Project description:The development of pancreatic ductal adenocarcinoma (PDAC) is heavily influenced by local stromal tissues, or desmoplasia. Biomimetic hydrogels capable of mimicking tumor niches are particularly useful for discovering the role of independent matrix cues on cancer cell development. Here, we report a photo-curable and bio-orthogonal thiol-ene (i.e., cross-linked by mutually reactive norbornene and thiol groups via photoinitiation) hydrogel platform for studying the growth, morphogenesis, drug resistance, and cancer stem cell marker expression in PDAC cells cultured in 3D. The hydrogels were prepared from multi-arm poly(ethylene glycol)-norbornene cross-linked with protease-sensitive peptide to permit cell-mediated matrix remodeling. Collagen 1 fibrils were incorporated into the covalent network while cytokines (e.g., EGF and TGF-β1) were supplemented in the culture media for controlling cell fate. We found that the presence of collagen 1 enhanced cell proliferation and Yes-associated protein (YAP) translocation to cell nuclei. Cytokines and collagen 1 synergistically up-regulated MT1-MMP expression and induced cell spreading, suggestive of epithelial-mesenchymal transition (EMT) in the encapsulated cells. Furthermore, PDAC cells cultured in 3D developed chemo-resistance even in the absence of collagen 1 and cytokines. This phenotype is likely a consequence of the enrichment of pancreatic cancer stem cells that expressed high levels of CD24, sonic hedgehog (SHH), and vascular endothelial growth factor (VEGF).
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