Publications
62 results found
Qin M, Tai GP, Collas P, et al., 2009, Cell extract-derived differentiation of embryonic stem cells, STEM CELLS, Vol: 23, Pages: 712-718, ISSN: 1066-5099
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- Citations: 63
Siti-Ismail N, Bishop AE, Polak JM, et al., 2008, The benefit of human embryonic stem cell encapsulation for prolonged feeder-free maintenance, BIOMATERIALS, Vol: 29, Pages: 3946-3952, ISSN: 0142-9612
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- Citations: 138
Rippon HJ, Lane S, Qin M, et al., 2008, Embryonic stem cells as a source of pulmonary epithelium in vitro and in vivo., Proc Am Thorac Soc, Vol: 5, Pages: 717-722, ISSN: 1546-3222
Embryonic stem cells (ESCs) derived from the preimplantation blastocyst are pluripotent and capable of indefinite expansion in vitro. As such, they present a cell source to derive a potentially inexhaustible supply of pulmonary cells and tissue. ESC-derived pulmonary epithelium could be used for in vitro cell or tissue models or, in the future, implanted into the damaged or diseased lung to effect repair. Efforts to date have largely focused on obtaining distal lung epithelial phenotypes from ESCs, notably alveolar epithelium. Several disparate methods have been developed to enhance differentiation of ESCs into pulmonary epithelial lineages; these are broadly based on recapitulating developmental signaling events, mimicking the physical environment, or forcibly reprogramming the ESC nucleus. Early findings of our preclinical experiments implanting differentiated ESCs into the injured lung are also described here. Future efforts will focus on maximizing ESC differentiation efficiency and yield of the target phenotype, as well as characterizing the function of derived cells in vivo and in vitro.
Hwang Y-S, Bishop AE, Polak JM, et al., 2007, Enhanced <i>in vitro</i> chondrogenic differentiation of murine embryonic stem cells, BIOTECHNOLOGY AND BIOPROCESS ENGINEERING, Vol: 12, Pages: 696-706, ISSN: 1226-8372
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- Citations: 4
Lane S, Rippon H, Takata M, et al., 2007, Mouse embryonic stem cell engrafment in healthy and injured mouse lung, Conference of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS-EU), Publisher: MARY ANN LIEBERT INC, Pages: 1731-1731, ISSN: 1076-3279
Lane S, Rippon HJ, Bishop AE, 2007, Stem cells in lung repair and regeneration, REGENERATIVE MEDICINE, Vol: 2, Pages: 407-415, ISSN: 1746-0751
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- Citations: 15
Samadikuchaksaraei A, Bishop AE, 2007, Effects of growth factors on the differentiation of murine ESC into type II pneumocytes, CLONING AND STEM CELLS, Vol: 9, Pages: 407-416, ISSN: 1536-2302
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- Citations: 21
Samadikuchaksaraei A, Bishop AE, 2007, Recovery rate of embryonic stem cells after defrosting: role of the feeder layer, CYTOTHERAPY, Vol: 9, Pages: 697-698, ISSN: 1465-3249
Lin YM, Boccaccini AR, Polak JM, et al., 2006, Biocompatibility of poly-DL-lactic acid (PDLLA) for lung tissue engineering, JOURNAL OF BIOMATERIALS APPLICATIONS, Vol: 21, Pages: 109-118, ISSN: 0885-3282
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- Citations: 58
Bishop AE, Rippon HJ, 2006, Stem cells - potential for repairing damaged lungs and growing human lungs for transplant, EXPERT OPINION ON BIOLOGICAL THERAPY, Vol: 6, Pages: 751-758, ISSN: 1471-2598
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- Citations: 8
Cohen S, Samadikuchaksaraei A, Polak JM, et al., 2006, Antibiotics reduce the growth rate and differentiation of embryonic stem cell cultures, TISSUE ENGINEERING, Vol: 12, Pages: 2025-2030, ISSN: 2152-4947
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- Citations: 37
Vats A, Bielby RC, Tolley N, et al., 2006, Chondrogenic Differentiation of Human Embryonic Stem Cells: The Effect of the Micro-Environment., Tissue Eng, ISSN: 1076-3279
We have previously induced differentiation of embryonic stem cells (ESC) to specific phenotypes by manipulating the culture conditions, including the use of indirect co-culture. In this study, we hypothesized that co-culture with primary chondrocytes can induce human embryonic stem cells (hESC) to differentiate towards the chondrocyte lineage. Co-cultures of hESC and chondrocytes were established using well inserts, with control comprising hESC grown alone or with fibroblasts. After 28 days, after removal of the chondrocyte inserts, hESC differentiation was assessed, by morphology, immunocytochemistry, and reverse transcription polymerase chain reaction. hESC, co-cultured or grown alone, were also implanted into SCID mice on a poly-D, L-lactide scaffold, harvested 35 days later and assessed in the same way. hESC co-cultured with chondrocytes formed colonies and secreted extracellular matrix containing glycosaminoglycans (GAG). Quantitative assay showed increased synthesis of sulfated GAG in co-culture as compared with control hESC grown alone for the same period (p < 0.0001). In addition, co-cultured hESC expressed Sox 9 and collagen type II, unlike control hESC. Co-culture with fibroblasts did not induce chondrogenic differentiation. The implanted constructs with co-cultured hESC contained significantly more type II collagen (p < 0.01), type I collagen (p < 0.05), total collagen (p < 0.01), and GAG (p < 0.01) than those with hESC grown alone. Thus, we show for the first time differentiation of hESC to chondrocytes. Our results confirm the potential of the culture micro-environment to influence ESC differentiation and could provide the basis for future generation of chondrogenic cells for use in tissue repair and increase our understanding of the mechanisms that direct differentiation.
Cohen S, Samadikuchaksaraei A, Polak JM, et al., 2006, Antibiotics Reduce the Growth Rate and Differentiation of Embryonic Stem Cell Cultures., Tissue Eng, ISSN: 1076-3279
Embryonic stem cells (ESCs) are being investigated increasingly for their potential as a cell source for tissue engineering. Antibiotics are regularly used in ESC culture media to control contamination, although they can be cytotoxic and interfere with protein synthesis. Our aim was to examine the effects of the frequently used antibiotics gentamicin and combined penicillin and streptomycin on ESC culture using differentiation of murine ESC into type II pneumocytes as a model. Antibiotics reduced the expression of the specific marker for type II pneumocytes, SPC mRNA, by up to 60%. We also identified an adverse effect on the growth rate of differentiating embryoid bodies, causing a significant ( p < 0.05) reduction of up to 40%, and an increase in population doubling time of up to 48%. No contamination was seen in any of the cultures. Our findings suggest that the routine use of antibiotics in ESC culture should be avoided as it may reduce the efficiency of the culture system.
Vats A, Bielby RC, Tolley N, et al., 2006, Chondrogenic differentiation of human embryonic stem cells: The effect of the micro-environment, TISSUE ENGINEERING, Vol: 12, Pages: 1687-1697, ISSN: 1076-3279
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- Citations: 132
Rippon HJ, Polak JM, Qin M, et al., 2006, Derivation of distal lung epithelial progenitors from murine embryonic stem cells using a novel three-step differentiation protocol, STEM CELLS, Vol: 24, Pages: 1389-1398, ISSN: 1066-5099
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- Citations: 93
Qin M, Tai G, Collas P, et al., 2006, Cell extract-based re-programming of embryonic stem cells to promote lineage-specific differentiation, 8th Annual Meeting of the Tissue-Engineering-Society-International (TESI), Publisher: MARY ANN LIEBERT, INC, Pages: 1050-1051, ISSN: 2152-4947
Samadikuchaksaraei A, Cohen S, Isaac K, et al., 2006, Derivation of distal airway epithelium from human embryonic stem cells, TISSUE ENGINEERING, Vol: 12, Pages: 867-875, ISSN: 2152-4947
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- Citations: 95
Edgar AJ, Chacon MR, Bishop AE, et al., 2006, Upregulated genes in sporadic, idiopathic pulmonary arterial hypertension, Respiratory Research, Vol: 7, ISSN: 1465-993X
BackgroundTo elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH).MethodsPeripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test.ResultsWe present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase.ConclusionFour of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.
Samadikuchaksaraei A, Bishop AE, 2006, Derivation and characterization of alveolar epithelial cells from murine embryonic stem cells in vitro., Methods Mol Biol, Vol: 330, Pages: 233-248, ISSN: 1064-3745
We present a protocol that has been developed for induction of the differentiation of murine embryonic stem (ES) cells to alveolar type II cells. With this protocol, undifferentiated murine ES cells are induced to form embryoid bodies (EBs). The 10-d-old EBs are transferred to adherent culture conditions and are fed with high-glucose Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% v/v fetal bovine serum, 2 mM L-glutamine, and 0.1 mM 2-mercaptoethanol for 20 d without splitting. Then, the cells are fed with a medium designed for the maintenance and growth of mature distal airway epithelial cells (small airway growth medium, SAGM) for 3 d. Characterization of the alveolar type II cells was done using real-time reverse transcriptase polymerase chain reaction detection of surfactant protein C mRNA and immunocytochemical detection of prosurfactant protein C. Real-time reverse transcriptase polymerase chain reaction revealed that SAGM increases the mRNA expression level of SPC by a factor of 8 when compared to that of cells grown in supplemented high-glucose DMEM (p < 0.05, Student t-test). Immunocytochemistry revealed that proSPC-expressing cells comprised 2.8 +/- 0.23% of the total cell population in SAGM-treated samples and 0.5 +/- 0.1% in samples treated with supplemented high-glucose DMEM (p < 0.05, chi2 test).
Polak JM, Bishop AE, 2006, Stem cells and tissue engineering: Past, present, and future, SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING, Vol: 1068, Pages: 352-366, ISSN: 0077-8923
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- Citations: 95
Bishop AE, Polak JM, 2006, Pulmonary epithelium, EMBRYONIC STEM CELLS, Vol: 418, Pages: 333-349, ISSN: 0076-6879
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- Citations: 1
Albera C, Bishop AE, Polak JM, et al., 2005, Human CD34<SUP>+</SUP> haematopoietic stem cells (HSC) from umbilical cord blood display an endodermal phenotype when exposed to Activin A <i>in vitro</i>., 47th Annual Meeting of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, Pages: 484A-484A, ISSN: 0006-4971
Tai GP, Christodoulou I, Bishop AE, et al., 2005, Use of green fluorescent fusion protein to track activation of the transcription factor osterix during early osteoblast differentiation, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 333, Pages: 1116-1122, ISSN: 0006-291X
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- Citations: 27
Vats A, Tolley NS, Bishop AE, et al., 2005, Embryonic stem cells and tissue engineering: delivering stem cells to the clinic, JOURNAL OF THE ROYAL SOCIETY OF MEDICINE, Vol: 98, Pages: 346-350, ISSN: 0141-0768
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- Citations: 47
Van Vranken BE, Romanska HR, Polak JM, et al., 2005, Co-culture of embryonic stem cells with pulmonary mesenchyme: a microenvironment that promotes differentiation of pulmonary epithelium., Tissue Engineering, Vol: 11
Albera C, Polak JM, Janes S, et al., 2005, Repopulation of human pulmonary epithelium by bone marrow cells: a potential means to promote repair., Tissue Engineering, Vol: 11
Rippon HJ, Polak JM, Bishop AE, 2005, Induction of distal lung epithelial markers by stepwise differentiation of mouse embryonic stem cells, Autumn Meeting of the British-Society-for-Matrix-Biology, Publisher: BLACKWELL PUBLISHING, Pages: A21-A21, ISSN: 0959-9673
Bardhan KD, Bishop AE, Polak JM, et al., 2005, Pantoprazole in severe acid-peptic disease: the effectiveness and safety of 5 years' continuous treatment, American-Gastroenterological-Association Meeting, Publisher: ELSEVIER SCIENCE INC, Pages: 10-22, ISSN: 1590-8658
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- Citations: 14
Tai GP, Polak JM, Bishop AE, et al., 2004, Differentiation of osteoblasts from murine embryonic stem cells by overexpression of the transcriptional factor osterix, TISSUE ENGINEERING, Vol: 10, Pages: 1456-1466, ISSN: 2152-4947
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- Citations: 66
Rippon HJ, Ali NN, Polak JM, et al., 2004, Initial observations on the effect of medium composition on the differentiation of murine embryonic stem cells to alveolar type II cells, CLONING AND STEM CELLS, Vol: 6, Pages: 49-56, ISSN: 1536-2302
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- Citations: 51
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