| p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo.
October 28, 2009 at 9:30 am
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| | p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo. Proc Natl Acad Sci U S A. 2009 Oct 26; Authors: Liu M, Casimiro MC, Wang C, Shirley LA, Jiao X, Katiyar S, Ju X, Li Z, Yu Z, Zhou J, Johnson M, Fortina P, Hyslop T, Windle JJ, Pestell RG p21(CIP1/WAF1) is a downstream effector of tumor suppressors and functions as a cyclin-dependent kinase inhibitor to block cellular proliferation. Breast tumors may derive from self-renewing tumor-initiating cells (BT-ICs), which contribute to tumor progression, recurrence, and therapy resistance. The role of p21(CIP1) in regulating features of tumor stem cells in vivo is unknown. Herein, deletion of p21(CIP1), which enhanced the rate of tumorigenesis induced by mammary-targeted Ha-Ras or c-Myc, enhanced gene expression profiles and immunohistochemical features of epithelial mesenchymal transition (EMT) and putative cancer stem cells in vivo. Silencing of p21(CIP1) enhanced, and expression of p21(CIP1) repressed, features of EMT in transformed immortal human MEC lines. p21(CIP1) attenuated oncogene-induced BT-IC and mammosphere formation. Thus, the in vitro cell culture assays reflect the changes observed in vivo in transgenic mice. These findings establish a link between the loss of p21(CIP1) and the acquisition of breast cancer EMT and stem cell properties in vivo. PMID: 19858489 [PubMed - as supplied by publisher] |
| Osteogenic differentiation of human amniotic fluid-derived stem cells induced by bone morphogenetic protein-7 and enhanced by nanofibrous scaffolds.
October 28, 2009 at 9:30 am
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| | Osteogenic differentiation of human amniotic fluid-derived stem cells induced by bone morphogenetic protein-7 and enhanced by nanofibrous scaffolds. Biomaterials. 2009 Oct 24; Authors: Sun H, Feng K, Hu J, Soker S, Atala A, Ma PX Amniotic fluid-derived stem cells (AFSCs) are becoming an important source of cells for regenerative medicine given their apparent advantages of accessibility, renewal capacity and multipotentiality. In the intermediate stage between the embryonic stem cells (ESCs) and adult stem cells, AFSCs may have a distinct mechanism to choose their fate. Unfortunately, until now, little is known about how bone morphogenetic proteins (BMPs) control the osteoblastic differentiation of AFSCs, especially on 3D scaffolds. Our research shows that human AFSCs (hAFSCs) can be induced for osteoblastic differentiation by rhBMP-7, and hAFSCs respond to rhBMP-7 more strongly than human mesenchymal stem cells (hMSCs). As synthetic ECM, scaffolds play a central role in tissue engineering. The hAFSCs, on the nanofibrous scaffolds (NF scaffolds) with morphology similar to that of natural collagen fibers, showed significantly enhanced alkaline phosphatase (ALP) activity, calcium content, von Kossa staining and the expression of osteogenic genes than those on the traditional scaffolds, i.e. solid walled scaffolds. The data on the bone formation in vivo presented further evidence that biomimetic NF scaffolds provided hAFSCs a more favorable synthetic ECM, and thus, facilitated the osteogenic differentiation of hAFSCs. The relative strong responsiveness to rhBMP-7 makes hAFSCs promising in bone regeneration. The synthetic NF scaffolds, which mimic the morphology of natural collagen fibers, enhanced the osteoblastic differentiation of hAFSCs in vitro and bone formation in vivo. PMID: 19857889 [PubMed - as supplied by publisher] |
| Stem Cell Therapy for the Broken Heart: Mini-Organ Transplantation.
October 28, 2009 at 9:30 am
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| | Stem Cell Therapy for the Broken Heart: Mini-Organ Transplantation. Transplant Proc. 2009 Oct;41(8):3353-3357 Authors: Mansour S, Roy DC, Lemieux B, Ouellet C, Stevens LM, Noiseux N BACKGROUND: Myocardial infarction (MI) is characterized by irreversible loss of cardiomyocytes, resulting in impaired ventricular function. Stem cell therapy using autologous progenitor cells has emerged as a promising approach. Experimental studies have demonstrated that highly selected hematopoeitic stem cells, which are characterized by the presence of the surface markers CD34 and CD133, may contribute to repair of the acutely infarcted myocardium by inducing neovascularization, inhibiting apoptosis, and promoting cardiomyogenesis. We sought, to evaluate the intracoronary injection of CD133(+) stem cells for cardiac repair in patients with dysfunctional myocardium after an acute MI. PATIENTS AND METHODS: In this Canadian randomized, double-blind, placebo-controlled, Phase I-II study ("COMPARE-AMI"), we are evaluating the feasibility, safety, and efficacy of intracoronary injection of selected CD133(+) stem cells for cardiac repair in patients with impaired cardiac function after successfully stented acute MI. Since November 2007, we have enrolled 14 patients in the study. Their mean age was 50.5 +/- 9.1 years, including 93% men. The culprit lesion was always on the left anterior descending artery (LAD). Their maximum troponin and CKMB levels were 8.4 +/- 6.1 mug/L and 322 +/- 225 U/L, respectively. RESULTS: Compared with the baseline, we observed a significant 8.7% improvement in left ventricular ejection fraction at 4 months follow-up, namely, from 41.3 +/- 5.5% to 50.0 +/- 8.2% (n = 7; P = .008). There were no protocol-related complications. Our trial is designed to recruit 40 patients who are randomized 1:1 to receive CD133(+) cells or placebo. PERSPECTIVE: There is a need to seek out new therapeutics for the treatment of ischemic heart disease addressing the early loss of viable myocytes. Stem cell transplantation has shown early promise; this appraisal needs well-designed, controlled studies. PMID: 19857748 [PubMed - as supplied by publisher] |
| Cryopreservation of primate embryonic stem cells with chemically-defined solution without Me(2)SO.
October 28, 2009 at 9:30 am
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| | Cryopreservation of primate embryonic stem cells with chemically-defined solution without Me(2)SO. Cryobiology. 2009 Oct 23; Authors: Nishigaki T, Teramura Y, Suemori H, Iwata H Human embryonic stem (hES) cells are expected to be useful in the fields of regenerative medicine and tissue engineering due to their pluripotency. Therefore, it is necessary to establish highly efficient and reliable methods for the cryopreservation of hES cells. We have cryopreserved cynomolgus and human ES cells by the vitrification method, using a chemically-defined dimethyl sulfoxide (Me(2)SO)-free and serum-free medium composed of Euro-Collins solution as a base medium and 40% (v/v) ethylene glycol (EG) and 10% (w/v) polyethylene glycol (PEG) as cryoprotectants. When the vitrification and the cryoprotectants were combined, the recovery ratio of hES cells was 22.9 + 7.7%, compared to 0.4 + 0.2% when the conventional slow-freezing method was used. After the cryopreservation and thawing cycle, hES cells were easily cultured and expressed undifferentiated cell markers such as Nanog, Oct-4, SSEA-4, and alkaline phosphatase activity after several subculturing steps. We also found that the pluripotency of hES cells was maintained, as demonstrated by teratoma formation of ES cells transplanted into severe combined immunodeficient (SCID) mice. Thus, we conclude that we have successfully cryopreserved primate ES cells with high efficiency using a Me(2)SO-free, chemically-defined medium. PMID: 19857481 [PubMed - as supplied by publisher] |
| The use of fluorochrome labels for in vivo bone tissue engineering research.
October 28, 2009 at 9:30 am
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| | The use of fluorochrome labels for in vivo bone tissue engineering research. Tissue Eng Part B Rev. 2009 Oct 26; Authors: van Gaalen SM, Kruyt M, Geuze R, de Bruijn J, Alblas J, Dhert W The use of fluorochromes in bone research is a widely accepted technique that dates back to the 1950s. Several pioneers, such as Harold Frost, have thoroughly investigated the potential of fluorochrome use for the study on bone formation and bone remodeling dynamics. Since the development of bone tissue engineering, a renewed interest in the benefits of fluorochrome use is perceived. Fluorochrome use in animal models makes it possible to determine the onset time and location of osteogenesis, fundamental parameters in bone tissue engineering studies. There is however a lack of standardized procedures for using this technique. In addition, many types of fluorochromes exist and one could be confused upon selecting the appropriate type, the appropriate concentration, the route of administration and methods of visualization. All these variables can potentially affect the outcome during fluorescence microscopy. This work aims at providing the bone tissue engineering researcher with an overview of the history, working mechanism and the potential pitfalls in the use of fluorochromes in animal studies. Experiments using some of the more frequently used fluorochromes are explained and illustrated. PMID: 19857045 [PubMed - as supplied by publisher] |
| Overcoming diffusional limitations in vascular tissue engineering with transmural flow.
October 28, 2009 at 9:30 am
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| | Overcoming diffusional limitations in vascular tissue engineering with transmural flow. Biotechnol Bioeng. 2009 Oct 26;104(6):fmvii Authors: PMID: 19859989 [PubMed - as supplied by publisher] |
| Non Cell-Autonomous Reprogramming of Adult Ocular Progenitors: Generation of Pluripotent Stem Cells Without Exogenous Transcription Factors.
October 28, 2009 at 9:30 am
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| | Non Cell-Autonomous Reprogramming of Adult Ocular Progenitors: Generation of Pluripotent Stem Cells Without Exogenous Transcription Factors. Stem Cells. 2009 Oct 26; Authors: Balasubramanian S, Babai N, Chaudhuri A, Qiu F, Bhattacharya S, Dave B, Parameswaran S, Carson S, Thoreson WB, Sharp JG, Rao M, Ahmad I Direct reprogramming of differentiated cells to induced pluripotent stem (iPS) cells by ectopic expression of defined transcription factors (TFs) represents a significant breakthrough towards the use of stem cells in regenerative medicine[1]. However, the virus-mediated expression of exogenous transcription factors could be potentially harmful and therefore, represents a barrier to the clinical use of iPS cells. Several approaches, ranging from plasmid mediated TF expression to introduction of recombinant TFs [2,3], have been reported to address the risk associated with viral integration. We describe an alternative strategy of reprogramming somatic progenitors entirely through the recruitment of endogenous genes without the introduction of genetic materials or exogenous factors. To this end, reprogrammed accessible and renewable progenitors from the limbal epithelium of adult rat eye by microenvironment-based induction of endogenous iPS cell genes. Non cell-autonomous reprogramming generates cells that are pluripotent and capable of differentiating into functional neurons, cardiomyocytes and hepatocytes, which may facilitate autologous cell therapy to treat degenerative diseases. PMID: 19859985 [PubMed - as supplied by publisher] |
| Microstructure and properties of nano-fibrous PCL-b-PLLA scaffolds for cartilage tissue engineering.
October 28, 2009 at 9:30 am
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| | Microstructure and properties of nano-fibrous PCL-b-PLLA scaffolds for cartilage tissue engineering. Eur Cell Mater. 2009;18:63-74 Authors: He L, Liu B, Xipeng G, Xie G, Liao S, Quan D, Cai D, Lu J, Ramakrishna S Nano-fibrous scaffolds which could potentially mimic the architecture of extracellular matrix (ECM) have been considered a good candidate matrix for cell delivery in tissue engineering applications. In the present study, a semicrystalline diblock copolymer, poly(e-caprolactone)-block-poly(L-lactide) (PCL-b-PLLA), was synthesized and utilized to fabricate nano-fibrous scaffolds via a thermally induced phase separation process. Uniform nano-fibrous networks were created by quenching a PCL-b-PLLA/THF homogenous solution to -20 degrees C or below, followed by further gelation for 2 hours due to the presence of PLLA and PCL microcrystals. However, knot-like structures as well as continuously smooth pellicles appeared among the nano-fibrous network with increasing gelation temperature. DSC analysis indicated that the crystallization of PCL segments was interrupted by rigid PLLA segments, resulting in an amorphous phase at high gelation temperatures. Combining TIPS (thermally induced phase separation) with salt-leaching methods, nano-fibrous architecture and interconnected pore structures (144+/-36 mm in diameter) with a high porosity were created for in vitro culture of chondrocytes. Specific surface area and protein adsorption on the surface of the nano-fibrous scaffold were three times higher than on the surface of the solid-walled scaffold. Chondrocytes cultured on the nano-fibrous scaffold exhibited a spherical condrocyte-like phenotype and secreted more cartilage-like extracellular matrix (ECM) than those cultured on the solid-walled scaffold. Moreover, the protein and DNA contents of cells cultured on the nano-fibrous scaffold were 1.2-1.4 times higher than those on the solid-walled scaffold. Higher expression levels of collagen II and aggrecan mRNA were induced on the nano-fibrous scaffold compared to on the solid-walled scaffold. These findings demonstrated that scaffolds with a nano-fibrous architecture could serve as superior scaffolds for cartilage tissue engineering. PMID: 19859871 [PubMed - as supplied by publisher] |
| Induced pluripotent stem cells and reprogramming: seeing the science through the hype.
October 28, 2009 at 9:30 am
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| | Induced pluripotent stem cells and reprogramming: seeing the science through the hype. Nat Rev Genet. 2009 Oct 27; Authors: Belmonte JC, Ellis J, Hochedlinger K, Yamanaka S No-one can have failed to notice the splash that induced pluripotent stem (iPS) cells have made in the few years since somatic cells were first reprogrammed to pluripotency. But what is their real promise, where should research efforts be focused, and are we at a stage where we can replace embryonic stem cells? Four pioneering iPS cell researchers offer their personal insights into these and other questions of current debate. As well expressing hope for the improved understanding and treatment of human disease, they urge caution over safety and propose the establishment of iPS cell banks. PMID: 19859062 [PubMed - as supplied by publisher] | | | 
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