Spelling suggestions: "subject:"stemcell"" "subject:"stempell""
71 |
Osteogenic Differentiation from Mouse Embryonic Stem Cells and the Role of CalreticulinYu, Yanhong 11 December 2013 (has links)
Calreticulin, an endoplasmic reticulum (ER)-resident protein, is a calcium buffering chaperone. In this study, with an optimized differentiation protocol from mouse R1 ES cells, we demonstrate a novel role of calreticulin in osteogenic commitment and differentiation. To enhance the efficacy of the method, we manipulated cell density and examined the addition of retinoic acid, dexamethasone and peroxisome proliferator-activated receptor γ. The regimen consisting of seeding 250 cells per embryoid body, with the addition of RA (from day 3 to 5) and Dex (from day 10 to 21) gave the most efficacious output. Using this optimized protocol, we investigated the potential involvement of calreticulin in osteogenesis. Calreticulin knock-out cells displayed impaired osteogenesis compared to wild-type cells. In particular, the nuclear translocation of the runt-domain related transcription factor 2 and Osterix, were impaired in the absence of calreticulin. The stimulatory effect of calreticulin on osteogenesis was mediated by its calcium buffering function.
|
72 |
Osteogenic Differentiation from Mouse Embryonic Stem Cells and the Role of CalreticulinYu, Yanhong 11 December 2013 (has links)
Calreticulin, an endoplasmic reticulum (ER)-resident protein, is a calcium buffering chaperone. In this study, with an optimized differentiation protocol from mouse R1 ES cells, we demonstrate a novel role of calreticulin in osteogenic commitment and differentiation. To enhance the efficacy of the method, we manipulated cell density and examined the addition of retinoic acid, dexamethasone and peroxisome proliferator-activated receptor γ. The regimen consisting of seeding 250 cells per embryoid body, with the addition of RA (from day 3 to 5) and Dex (from day 10 to 21) gave the most efficacious output. Using this optimized protocol, we investigated the potential involvement of calreticulin in osteogenesis. Calreticulin knock-out cells displayed impaired osteogenesis compared to wild-type cells. In particular, the nuclear translocation of the runt-domain related transcription factor 2 and Osterix, were impaired in the absence of calreticulin. The stimulatory effect of calreticulin on osteogenesis was mediated by its calcium buffering function.
|
73 |
Endothelial Progenitor Cells (EPCs) for Fracture Healing and Angiogenesis: A Comparison with Mesenchymal Stem Cells (MSCs)Nauth, Aaron 21 March 2012 (has links)
The purpose of this study was to compare the effects of two types of stem/progenitor cells on the healing of critical sized bone defects in a rat model. Endothelial progenitor cells (EPCs), a novel cell type with previously demonstrated effects on both osteogenesis and angiogenesis, were compared to both a control group (no cells), and a treatment group of mesenchymal stem cells (MSCs). The hypothesis was that EPCs would demonstrate both superior bone healing and angiogenesis, when compared to MSCs and controls. EPCs, MSCs, or a control carrier were placed in surgically stabilized bone defects in a rat femur and both bone formation and angiogenesis were assessed. EPC treated defects demonstrated significantly more bone formation and angiogenesis at the bone defect site than MSC or control treated defects. These results strongly suggest that EPCs are more effective than MSCs for therapeutic osteogenesis and angiogenesis in a bone defect model.
|
74 |
Endothelial Progenitor Cells (EPCs) for Fracture Healing and Angiogenesis: A Comparison with Mesenchymal Stem Cells (MSCs)Nauth, Aaron 21 March 2012 (has links)
The purpose of this study was to compare the effects of two types of stem/progenitor cells on the healing of critical sized bone defects in a rat model. Endothelial progenitor cells (EPCs), a novel cell type with previously demonstrated effects on both osteogenesis and angiogenesis, were compared to both a control group (no cells), and a treatment group of mesenchymal stem cells (MSCs). The hypothesis was that EPCs would demonstrate both superior bone healing and angiogenesis, when compared to MSCs and controls. EPCs, MSCs, or a control carrier were placed in surgically stabilized bone defects in a rat femur and both bone formation and angiogenesis were assessed. EPC treated defects demonstrated significantly more bone formation and angiogenesis at the bone defect site than MSC or control treated defects. These results strongly suggest that EPCs are more effective than MSCs for therapeutic osteogenesis and angiogenesis in a bone defect model.
|
75 |
Novel Regulators of Somatic Cell ReprogrammingGolipour, Azadeh 09 January 2014 (has links)
Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by expression of defined embryonic factors. My thesis is focused on exploring the mechanisms underlying reprogramming using a secondary mouse embryonic fibroblast model that forms iPS cells with high efficiency upon inducible expression of Oct4, Klf4, c-Myc and Sox2. My analyses of the temporal changes in gene expression reveal that reprogramming is a multi-step process characterized by initiation, maturation and stabilization phases. Using functional RNAi screening, I discovered a key role for BMP signaling and the induction of mesenchymal-to-epithelial transition (MET) during the initiation phase. I showed that MET induction was linked to BMP-dependent induction of miR-205 and the miR-200 family of microRNAs. These studies thus defined a multi-step mechanism that incorporates a BMP-miRNA-MET axis during somatic cell reprogramming.
Next I focused on the two later phases of reprogramming, maturation and stabilization. I showed the stabilization phase and acquisition of pluripotency is dependent on removal of transgene expression late in the maturation phase. Clonal analysis of reprogramming cells revealed subsets of stabilization competent (SC) versus stabilization incompetent (SI) cells. SC clones robustly entered the pluripotent state upon transgene withdrawal in the late, but not early maturation phase, whereas SI clones failed to reprogram at either stage. Transcriptome profiling by RNA-Seq revealed that SC clones acquire a competency gene expression signature late in the maturation phase. Functional RNAi screening of SC signature genes further identified regulators of transition to the stabilization phase, while screening of the same signature in iPS cells revealed a distinct subset of genes required for maintenance of pluripotency. These studies reveal that the acquisition and subsequent maintenance of pluripotency are controlled by distinct molecular networks and uncover a novel regulatory program that is required for transition to transgene independence.
|
76 |
Novel Regulators of Somatic Cell ReprogrammingGolipour, Azadeh 09 January 2014 (has links)
Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by expression of defined embryonic factors. My thesis is focused on exploring the mechanisms underlying reprogramming using a secondary mouse embryonic fibroblast model that forms iPS cells with high efficiency upon inducible expression of Oct4, Klf4, c-Myc and Sox2. My analyses of the temporal changes in gene expression reveal that reprogramming is a multi-step process characterized by initiation, maturation and stabilization phases. Using functional RNAi screening, I discovered a key role for BMP signaling and the induction of mesenchymal-to-epithelial transition (MET) during the initiation phase. I showed that MET induction was linked to BMP-dependent induction of miR-205 and the miR-200 family of microRNAs. These studies thus defined a multi-step mechanism that incorporates a BMP-miRNA-MET axis during somatic cell reprogramming.
Next I focused on the two later phases of reprogramming, maturation and stabilization. I showed the stabilization phase and acquisition of pluripotency is dependent on removal of transgene expression late in the maturation phase. Clonal analysis of reprogramming cells revealed subsets of stabilization competent (SC) versus stabilization incompetent (SI) cells. SC clones robustly entered the pluripotent state upon transgene withdrawal in the late, but not early maturation phase, whereas SI clones failed to reprogram at either stage. Transcriptome profiling by RNA-Seq revealed that SC clones acquire a competency gene expression signature late in the maturation phase. Functional RNAi screening of SC signature genes further identified regulators of transition to the stabilization phase, while screening of the same signature in iPS cells revealed a distinct subset of genes required for maintenance of pluripotency. These studies reveal that the acquisition and subsequent maintenance of pluripotency are controlled by distinct molecular networks and uncover a novel regulatory program that is required for transition to transgene independence.
|
77 |
Optimal Population of Embryonic Stem Cells in "Hanging Drop" Culture for in-vitro Differentiation to Cardiac MyocytesMIWA, Keiko, LEE, Jong-Kook, HIDAKA, Kyoko, SHI, Rong-qian, MORISAKI, Takayuki, KODAMA, Itsuo 12 1900 (has links)
国立情報学研究所で電子化したコンテンツを使用している。
|
78 |
Studies in stem cell biology and developmental pathway regulation in the pancreas and breastO'Toole, Sandra Alison, Garvan Institute of Medical Research, Faculty of Medicine, UNSW January 2008 (has links)
Breast and pancreatic cancers are among the major causes of cancer mortality in our society. There has been a significant decline in mortality from breast cancer over the last two decades, while pancreatic cancer has an exceptionally poor prognosis. Although these malignancies have very different clinical outcomes they share the common feature that metastatic disease is almost uniformly fatal. The existence of cancer stem cells has been postulated as a major factor in tumour recurrence after traditional chemo- or radio-therapy. Addressing this important clinical question requires a deeper understanding of the biology of normal and cancer stem cells and the signalling pathways involved in their regulation. The identity of the pancreatic stem cell remains elusive. However, using a murine model of haematopoietic stem cell (HSC) transplantation I have demonstrated for the first time transdifferentiation of these bone marrow derived cells into mature pancreatic acinar cells, where they appear to contribute to cell turnover ultimately forming acini and lobules. These data show that HSC have surprising developmental plasticity and provide insight into a potential stem cell niche in the pancreas. The Hedgehog, Wnt and Notch signalling pathways play a critical role in early development and in the maintenance and self-renewal of stem cells. There is also increasing evidence that dysregulation of these pathways contributes to the development of many malignancies. There is relatively little information regarding their role in breast cancer development and progression. I used immunohistochemistry for key proteins in these pathways, sonic hedgehog, beta-catenin and Notch 1 in three substantial series of human breast lesions and determined that abnormal expression of these proteins is an early event in the development in breast cancer, and is associated with particular breast cancer subtypes, Shh and beta-catenin expression is associated predominantly with the basal-like phenotype and Notch 1 with the HER2 amplified phenotype. Overexpression of Shh in particular confers a worse clinical outcome in invasive ductal carcinoma. Furthermore, increased levels of Shh in a 3D culture model of non-transformed mammary epithelial cells resulted in disorganisation of acini and the development of an abnormal discohesive phenotype. Finally the role of Shh was investigated in a mammary epithelial transplantation model, where overexpression of Shh resulted in the development of hyperplasia of the mammary ductal epithelium. Together these data confirm that the Hedgehog, Wnt and Notch developmental pathways are dysregulated in breast cancer and represent viable targets for further investigation of potential novel therapies in breast cancer.
|
79 |
Risk-factors, prevention and treatment of early complications after allogeneic haematopoietic stem cell transplantation /Hägglund, Hans, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.
|
80 |
Molecular monitoring of engraftment and leukemia relapse after allogeneic hematopoietic stem cell transplantation /Mattsson, Jonas, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.
|
Page generated in 0.0298 seconds