Project description:Neonatal thymus MSCs and bone derived MSCs have differential abilities to stimulate angiogenesis and invade extracellular matrix. We utilized microarray to identify differentially expressed genes between these two types of MSCs and analyzed this information in the context of the phenotypic differences between these two cell types.
Project description:Although mesenchymal stem/stromal cells (MSCs) are being explored in numerous clinical trials as proangiogenic and proregenerative agents, the influence of tissue origin on the therapeutic qualities of these cells is poorly understood. Complicating the functional comparison of different types of MSCs are the confounding effects of donor age, genetic background, and health status of the donor. Leveraging a clinical setting where MSCs can be simultaneously isolated from discarded but healthy bone and thymus tissues from the same neonatal patients, thereby controlling for these confounding factors, we performed an in vitro and in vivo paired comparison of these cells. We found that both neonatal thymus (nt)MSCs and neonatal bone (nb)MSCs expressed different pericytic surface marker profiles. Further, ntMSCs were more potent in promoting angiogenesis in vitro and in vivo and they were also more motile and efficient at invading ECM in vitro. These functional differences were in part mediated by an increased ntMSC expression of SLIT3, a factor known to activate endothelial cells. Further, we discovered that SLIT3 stimulated MSC motility and fibrin gel invasion via ROBO1 in an autocrine fashion. Consistent with our findings in human MSCs, we found that SLIT3 and ROBO1 were expressed in the perivascular cells of the neonatal murine thymus gland and that global SLIT3 or ROBO1 deficiency resulted in decreased neonatal murine thymus gland vascular density. In conclusion, ntMSCs possess increased proangiogenic and invasive behaviors, which are in part mediated by the paracrine and autocrine effects of SLIT3.
Project description:Transcriptional profiling of COLO 320 xenograft tumor cells comparing control COLO 320 xenograft without co-implanted rat MSCs with COLO 320 xenograft with co-implanted rat MSCs. The latter makes co-implanted MSCs visualization possible by using MSCs labeled by GFP under FACS and single cell microscopy. Two-condition experiment, COLO 320 xenograft without rat MSCs [COLO320 MSC(-)] vs. COLO 320 xenograft with rat MSCs [COLO320 MSC(+)]. Biological replicates: 1 control, 1 sample, paired xengraft tumor cells grown and harvested from the same mouse host. One replicate per array.
Project description:Lung cancer is a highly malignant tumor and the majority of cancer-related deaths are due to metastasis. The tumor microenvironment (TME) plays a fundamental role in the metastatic spread of tumor cells. Among other stromal cells, mesenchymal stem cells (MSCs) are known to be present within the TME and to be involved in cancer progression. However the majority of previous studies have been performed on bone marrow-derived MSCs. To investigate the role of the TME on the pulmonary MSC phenotype, we compared the expression profile of paired MSCs isolated from lung tumor (T-) and normal adjacent tissues (N-) from lung carcinoma patients. We used microarray data to find differentially expressed genes between N- and T-MSCs and identified several genes associated with poor prognosis that are more highly expressed in T- than in N-MSCs and potentially involved in the MSC promotion of lung cancer metastasis.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression. Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs. Two-condition experiment, KP MSCs vs. 3A6 MSCs.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
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.
Project description:Transcriptional profiling of human MSCs comparing control MSCs with parathyroid hormone (PTH)-stimulated MSCs. PTH-stimulated MSCs were treated with 0.1 nM recombinant human PTH (N-terminal fragment, amino acids 1-34) for 48 hours. Human MSCs were isolated from a bone marrow sample obtained from a healthy adult volunteer. Two-condition experiment: control MSCs vs. PTH-stimulated MSCs. 1 control MSCs and 1 PTH-stimulated MSCs.