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| Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction.
February 20, 2010 at 6:52 AM
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| | Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction. J Biomed Biotechnol. 2010;2010:236147 Authors: Sharma R, Greenhough S, Medine CN, Hay DC The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such ! cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays. PMID: 20169088 [PubMed - in process] | | |
| Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine.
February 20, 2010 at 6:52 AM
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| | Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine. Cell Death Differ. 2010 Feb 19; Authors: Anastasia L, Pelissero G, Venerando B, Tettamanti G The possibility of reprogramming adult somatic cells into pluripotent stem cells (iPSCs) has generated a renewed interest into stem cell research and promises to overcome several key issues, including the ethical concerns of using human embryonic stem cells and the difficulty of obtaining large numbers of adult stem cells (Belmonte et al., Nat Rev Genet, 2009). This approach is also not free from challenges like the mechanism of the reprogramming process, which has yet to be elucidated, and the warranties for safety of generated pluripotent cells, especially in view of their possible therapeutic use. Very recently, several new reprogramming methods have surfaced, which seem to be more appropriate than genetic reprogramming. Particularly, chemically induced pluripotent cells (CiPSs), obtained with recombinant proteins or small synthetic molecules, may represent a valid approach, simpler and possibly safer than the other ones.Cell Death and Differentiation advance o! nline publication, 19 February 2010; doi:10.1038/cdd.2010.14. PMID: 20168332 [PubMed - as supplied by publisher] | | |
| Assessment and optimization of cell engraftment after transplantation into the heart.
February 20, 2010 at 6:52 AM
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| | Assessment and optimization of cell engraftment after transplantation into the heart. Circ Res. 2010 Feb 19;106(3):479-94 Authors: Terrovitis JV, Smith RR, Marbán E Abstract: Myocardial regeneration using stem and progenitor cell transplantation in the injured heart has recently become a major goal in the treatment of cardiac disease. Experimental studies and clinical applications have generally been encouraging, although the functional benefits that have been attained clinically are modest and inconsistent. Low cell retention and engraftment after myocardial delivery is a key factor limiting the successful application of cell therapy, irrespective of the type of cell or the delivery method. To improve engraftment, accurate methods for tracking cell fate and quantifying cell survival need to be applied. Several laboratory techniques (histological methods, real-time quantitative polymerase chain reaction, radiolabeling) have provided invaluable information about cell engraftment. In vivo imaging (nuclear medicine modalities, bioluminescence, and MRI) has the potential to provide quantitative information noninvasively, enabling! longitudinal assessment of cell fate. In the present review, we present several available methods for assessing cell engraftment, and we critically discuss their strengths and limitations. In addition to providing insights about the mechanisms mediating cell loss after transplantation, these methods can evaluate techniques for augmenting engraftment, such as tissue engineering approaches, preconditioning, and genetic modification, allowing optimization of cell therapies. PMID: 20167944 [PubMed - in process] | | |
| Proteases and receptors in the recruitment of endothelial progenitor cells in neovascularization.
February 20, 2010 at 6:52 AM
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| | Proteases and receptors in the recruitment of endothelial progenitor cells in neovascularization. Eur Cytokine Netw. 2009 Dec 1;20(4):207-19 Authors: Verloop RE, Koolwijk P, Zonneveld AJ, Hinsbergh VW Since the initial discovery of endothelial progenitor cells (EPC), and their promise in increasing angiogenesis and vasculogenesis, a myriad of papers have highlighted their potential application in experimental and clinical neovascularization and in tissue engineering. However, promising reports are contrasted by other studies that could not find a role for EPC in neovascularization. Presently, two types of endothelial progenitor cell populations are recognized. The first population provides early-outgrowth CD34+/VEGFR-2+ cells, or colony-forming unit endothelial cells (CFU-EC), which represent myeloid cells with some endothelial properties, but no ability to form endothelial colonies. They can stimulate neovascularization by paracrine means, but are not incorporated in the endothelial lining themselves. The second population generates the late-outgrowth endothelial colony-forming cells (ECFC) from a very scant blood-derived cell population. ECFC have a very high! proliferative potential, can insert into the endothelial lining of new blood vessels, and can also form endothelial tubes by themselves after stimulation with the proper angiogenic stimulus. This review surveys the mobilization of progenitor cells from the bone marrow, the homing of EPC (CFU-EC) to areas of neovascularization, and the participation of EPC (ECFC) in the endothelial lining of newly formed blood vessels. Specific emphasis has been placed on the role of proteases, which include serine proteases, including urokinase, L-cathepsin, and several ADAM- and matrix metalloproteinases. The specific properties of ECFC make them a potential source of cells for tissue engineering applications, but much has to be learned about their nature, origin and properties. PMID: 20167560 [PubMed - in process] | | |
| Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application.
February 20, 2010 at 6:52 AM
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| | Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application. Int J Oral Maxillofac Surg. 2010 Feb 16; Authors: Kokemueller H, Spalthoff S, Nolff M, Tavassol F, Essig H, Stuehmer C, Bormann KH, Rücker M, Gellrich NC The key elements for bioartificial bone formation in 3D matrices are large numbers of osteogenic cells and supplies of oxygen and nutrition. Vascularization becomes more important with the increasing size and complexity of seeded scaffolds required for clinical application in reconstructive craniomaxillofacial surgery. Prefabrication of vascularized bioartificial bone grafts in vivo might be an alternative to in vitro tissue engineering techniques. Two cylindrical beta-TCP-scaffolds (25mm long) were intraoperatively filled with autogenous bone marrow from the iliac crest for cell loading and implanted into the latissimus dorsi muscle in 12 sheep. To determine the effect of axial perfusion, one scaffold in each sheep was surgically supplied with a central vascular bundle. Sheep were killed 3 months after surgery. Histomorphometric analysis showed autogenous bone marrow from the iliac crest was an effective source of osteogenic cells and growth factors, inducing con! siderable ectopic bone growth in all implanted scaffolds. Bone growth, ceramic resorption and angiogenesis increased significantly with axial perfusion. The results encourage the application of prefabricated bioartificial bone for segmental mandibular reconstruction in man. In clinical practice, vascularized bioartificial bone grafts could change the principles of bone transplantation with minimal donor site morbidity and no shape or volume limitations. PMID: 20167453 [PubMed - as supplied by publisher] | | |
| [Present and future of cell therapy in burns.]
February 20, 2010 at 6:52 AM
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| | [Present and future of cell therapy in burns.] Pathol Biol (Paris). 2010 Feb 16; Authors: Bargues L, Prat M, Leclerc T, Bey E, Lataillade JJ Severe burned patients need definitive and efficient wound coverage. Outcome of massive burns has been improved by using cultured epithelial autografts (CEA). Despite fragility, percentages of success take, cost of treatment and long-term tendency to contracture, this surgical technique has been developed in few burn centres. First improvements were to combine CEA and dermis-like substitute. Cultured skin substitutes provide earlier skin closure and satisfying functional result. These methods have been used successfully in massive burns. Second improvement was to allow skin regeneration by using epidermal stem cells. Stem cells have capacity to differentiate into keratinocytes, to promote wound repair and to regenerate skin appendages. Human mesenchymal stem cells contribute to wound healing and were evaluated in cutaneous radiation syndrome. Skin regeneration and tissue engineering methods remain a complex challenge and offer the possibility of new treatment for ! injured and burned patients. PMID: 20167439 [PubMed - as supplied by publisher] | | |
| Patterned transgene expression in multiple channel bridges after spinal cord injury.
February 20, 2010 at 6:52 AM
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| | Patterned transgene expression in multiple channel bridges after spinal cord injury. Acta Biomater. 2010 Feb 15; Authors: De Laporte L, Huang A, Ducommun MM, Zelivyanska ML, Aviles MO, Adler AF, Shea LD Patterning of gene delivery on sub-millimeter length scales within tissue engineering scaffolds can provide a fundamental technology to recreate the complex architectures of tissues. Surface-mediated delivery of lipoplexes mixed with fibronectin was investigated to pattern vectors within 250 mum channels on poly (lactide-co-glycolide) (PLG) bridges. Initial studies performed in vitro on PLG surfaces indicated that a DNA density of 0.07 mug/mm(2) inside each channel with a weight ratio of DNA to fibronectin of 1:20 maximized the number of transfected cells and the levels of transgene expression. Patterned vectors encoding for nerve growth factor (NGF) resulted in localized neurite extension within the channel. Translation to 3D multiple channel bridges enabled patterned transfection of different vectors throughout the channels for ratios of DNA to fibronectin of 1:4 and multiple DNA depositions, with a large increase of neural cell bodies and neurite extension for ! delivery of DNA encoding for NGF. In vivo, the immobilization of non-viral vectors within the channels resulted in localized transfection within the pore structure of the bridge immediately around the channels of the bridge containing DNA. This surface immobilization strategy enables patterned gene delivery in vitro and in vivo on lengths scales of hundreds of microns and may find utility in strategies aims at regenerating tissues with complex architectures. PMID: 20167291 [PubMed - as supplied by publisher] | | |
| Adipose Tissue Engineering for Soft Tissue Regeneration.
February 20, 2010 at 6:52 AM
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| | Adipose Tissue Engineering for Soft Tissue Regeneration. Tissue Eng Part B Rev. 2010 Feb 18; Authors: Kang JH, Gimble J, Lee K, Marra K, Rubin PJ, Yoo J, Kaplan DL Current treatment modalities for soft tissue defects due to various pathologies and trauma include autologous grafting and commercially available fillers. However, these treatment methods present a number of challenges and limitations, such as donor site morbidity and volume loss over time. As such, improved therapeutic modalities need to be developed. Tissue engineering techniques offer novel solutions to these problems through development of bioactive tissue constructs that can regenerate adipose tissue both in structure and function. Recently, a number of studies have been designed to explore various methods to engineer human adipose tissue. This review will focus on these developments in the area of adipose tissue engineering for soft tissue replacement. The physiology of adipose tissue and current surgical therapies used to replace lost tissue volume, specifically in breast tissue, are introduced, and current biomaterials, cell sources, and tissue culture str! ategies are discussed. We discuss future areas of study in adipose tissue engineering. PMID: 20166810 [PubMed - as supplied by publisher] | | |
| Linker Chemistry Determines Secondary Structure of p53(14-29) in Peptide Amphiphile Micelles.
February 20, 2010 at 6:52 AM
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| | Linker Chemistry Determines Secondary Structure of p53(14-29) in Peptide Amphiphile Micelles. Bioconjug Chem. 2010 Feb 18; Authors: Missirlis D, Farine M, Kastantin M, Ananthanarayanan B, Neumann T, Tirrell M Biofunctional micelles formed via self-assembly of synthetic peptide-lipid conjugates are a class of promising biomaterials with applications in drug delivery and tissue engineering. The micelle building block, termed peptide amphiphile, consists of a lipid-like chain covalently linked through a spacer to a peptide headgroup. Self-assembly results in formation of a hydrophobic core surrounded by a dense shell with multiple, functional peptides. We report here on the effect that different linkers between a palmitic tail and a bioactive peptide (p53(14-29)) have on headgroup secondary structure. Peptide p53(14-29) may act as an inhibitor of the interaction between tumor suppressor p53 and human double minute-2 (hDM2) proteins by binding hDM2 in a partially helical form, leading to the release of p53 and the induction of apoptosis in certain tumors. Circular dichroism and fluorescence spectroscopy data revealed that the extent and type of secondary structure of p53(1! 4-29) are controlled through size and hydrogen bond potential of the linker. In addition, the structure of the self-assembled micelles was influenced through linker-dependent altered headgroup interactions. This study provides insight into the mechanisms through which headgroup structuring occurs on peptide amphiphile micelles, with implications on the bioactivity, stability, and morphology of the self-assembled entities. PMID: 20166676 [PubMed - as supplied by publisher] | | |
| Current strategies and applications of tissue engineering in dentistry--a review Part 2.
February 20, 2010 at 6:52 AM
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| | Current strategies and applications of tissue engineering in dentistry--a review Part 2. Dent Update. 2009 Dec;36(10):639-42, 644-6 Authors: Malhotra N, Kundabala M, Acharya S The three main key elements used in tissue engineering are the stem cells, morphogens and the scaffolds that, under a conductive external influence (environment) combine in the engineering of tissues. Part 1 of this two-part review article described in detail the various stem cells, morphogens and scaffolds that can be used in tissue engineering. This second article describes the various ways in which these three key elements can be used to engineer biological tissues. A number of strategies and technologies (Figure 1) such as, stem cell therapy, gene therapy, guided tissue regeneration, self-assembling systems, etc have been proposed. Clinical Relevance: The field of tissue engineering has recently shown promising results and good future prospects in dentistry for the development of restorations to replace lost tooth structure with a functional replacement. PMID: 20166382 [PubMed - in process] | | |
| Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology.
February 20, 2010 at 6:44 AM
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| | Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology. PLoS One. 2010;5(2):e9200 Authors: Wang S, Lu B, Girman S, Duan J, McFarland T, Zhang QS, Grompe M, Adamus G, Appukuttan B, Lund R BACKGROUND: Retinitis pigmentosa (RP) is characterized by progressive night blindness, visual field loss, altered vascular permeability and loss of central vision. Currently there is no effective treatment available except gene replacement therapy has shown promise in a few patients with specific gene defects. There is an urgent need to develop therapies that offer generic neuro-and vascular-protective effects with non-invasive intervention. Here we explored the potential of systemic administration of pluripotent bone marrow-derived mesenchymal stem cells (MSCs) to rescue vision and associated vascular pathology in the Royal College Surgeons (RCS) rat, a well-established animal model for RP. METHODOLOGY/PRINCIPAL FINDINGS: Animals received syngeneic MSCs (1x10(6) cells) by tail vein at an age before major photoreceptor loss. Principal results: both rod and cone photoreceptors were preserved (5-6 cells thick) at the time when control animal has a single layer of ph! otoreceptors remained; Visual function was significantly preserved compared with controls as determined by visual acuity and luminance threshold recording from the superior colliculus; The number of pathological vascular complexes (abnormal vessels associated with migrating pigment epithelium cells) and area of vascular leakage that would ordinarily develop were dramatically reduced; Semi-quantitative RT-PCR analysis indicated there was upregulation of growth factors and immunohistochemistry revealed that there was an increase in neurotrophic factors within eyes of animals that received MSCs. CONCLUSIONS/SIGNIFICANCE: These results underscore the potential application of MSCs in treating retinal degeneration. The advantages of this non-invasive cell-based therapy are: cells are easily isolated and can be expanded in large quantity for autologous graft; hypoimmunogenic nature as allogeneic donors; less controversial in nature than other stem cells; can be readministered with! minor discomfort. Therefore, MSCs may prove to be the ideal c! ell sour ce for auto-cell therapy for retinal degeneration and other ocular vascular diseases. PMID: 20169166 [PubMed - in process] | | |
| Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer.
February 20, 2010 at 6:44 AM
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| | Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nat Rev Cancer. 2010 Feb 19; Authors: Jenq RR, van den Brink MR The year 2009 marked the fiftieth anniversary of the first successful allogeneic haematopoietic stem cell transplant (HSCT). The field of HSCT has pioneered some of the most exciting areas of research today. HSCT was the original stem cell therapy, the first cancer immune therapy and the earliest example of individualized cancer therapy. In this Timeline article we review the history of the development of HSCT and major advances made in the past 50 years. We highlight accomplishments made by researchers who continue to strive to improve outcomes for patients and increase the availability of this potentially life-saving therapy for patients with otherwise incurable malignancies. PMID: 20168320 [PubMed - as supplied by publisher] | | |
| Current strategies and applications of tissue engineering in dentistry--a review Part 2.
February 20, 2010 at 6:44 AM
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| | Current strategies and applications of tissue engineering in dentistry--a review Part 2. Dent Update. 2009 Dec;36(10):639-42, 644-6 Authors: Malhotra N, Kundabala M, Acharya S The three main key elements used in tissue engineering are the stem cells, morphogens and the scaffolds that, under a conductive external influence (environment) combine in the engineering of tissues. Part 1 of this two-part review article described in detail the various stem cells, morphogens and scaffolds that can be used in tissue engineering. This second article describes the various ways in which these three key elements can be used to engineer biological tissues. A number of strategies and technologies (Figure 1) such as, stem cell therapy, gene therapy, guided tissue regeneration, self-assembling systems, etc have been proposed. Clinical Relevance: The field of tissue engineering has recently shown promising results and good future prospects in dentistry for the development of restorations to replace lost tooth structure with a functional replacement. PMID: 20166382 [PubMed - in process] | | |
| Hematopoiesis from pluripotent stem cell lines.
February 20, 2010 at 6:38 AM
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| | Hematopoiesis from pluripotent stem cell lines. Int J Hematol. 2010 Feb 20; Authors: Sakamoto H, Tsuji-Tamura K, Ogawa M Embryonic stem cells (ESCs) can differentiate into various types of hematopoietic cells (HPCs) when placed in an appropriate environment. Various methods for the differentiation of ESCs into specific HPC lineages have been developed using mouse ESCs. These ESC-differentiation methods have been utilized also as an in vitro model to investigate hematopoiesis in embryos and they provided critical perceptions into it. These methods have been adapted for use with human ESCs, which have the possibility of being employed in regenerative medicine; further improvement of these methods may lead to the efficient production of HPCs for use in transfusions. The generation of transplantable hematopoietic stem cells is a medical goal that is still difficult to achieve. Recently, induced pluripotent stem (iPS) cells have been established from differentiated cells. Thereby, iPS cells have expanded further possibilities of the use of pluripotent stem cell lines in clinical applicat! ion. Indeed, iPS cells have been established from cells with disease genes and those which have undergone reprogramming and targeting have generated phenotypically normal HPCs. Here, we mainly summarize the recent progress in research on hematopoiesis conducted with ESCs and iPS cells. PMID: 20169427 [PubMed - as supplied by publisher] | | |
| Liver development, regeneration, and carcinogenesis.
February 20, 2010 at 6:38 AM
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| | Liver development, regeneration, and carcinogenesis. J Biomed Biotechnol. 2010;2010:984248 Authors: Kung JW, Currie IS, Forbes SJ, Ross JA The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in! all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers. PMID: 20169172 [PubMed - in process] | | |
| Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction.
February 20, 2010 at 6:38 AM
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| | Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction. J Biomed Biotechnol. 2010;2010:236147 Authors: Sharma R, Greenhough S, Medine CN, Hay DC The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such ! cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays. PMID: 20169088 [PubMed - in process] | | |
| Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine.
February 20, 2010 at 6:38 AM
|
| | Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine. Cell Death Differ. 2010 Feb 19; Authors: Anastasia L, Pelissero G, Venerando B, Tettamanti G The possibility of reprogramming adult somatic cells into pluripotent stem cells (iPSCs) has generated a renewed interest into stem cell research and promises to overcome several key issues, including the ethical concerns of using human embryonic stem cells and the difficulty of obtaining large numbers of adult stem cells (Belmonte et al., Nat Rev Genet, 2009). This approach is also not free from challenges like the mechanism of the reprogramming process, which has yet to be elucidated, and the warranties for safety of generated pluripotent cells, especially in view of their possible therapeutic use. Very recently, several new reprogramming methods have surfaced, which seem to be more appropriate than genetic reprogramming. Particularly, chemically induced pluripotent cells (CiPSs), obtained with recombinant proteins or small synthetic molecules, may represent a valid approach, simpler and possibly safer than the other ones.Cell Death and Differentiation advance o! nline publication, 19 February 2010; doi:10.1038/cdd.2010.14. PMID: 20168332 [PubMed - as supplied by publisher] | | |
| Zac1 Is an Essential Transcription Factor for Cardiac Morphogenesis.
February 20, 2010 at 6:38 AM
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| | Zac1 Is an Essential Transcription Factor for Cardiac Morphogenesis. Circ Res. 2010 Feb 18; Authors: Yuasa S, Onizuka T, Shimoji K, Ohno Y, Kageyama T, Yoon SH, Egashira T, Seki T, Hashimoto H, Nishiyama T, Kaneda R, Murata M, Hattori F, Makino S, Sano M, Ogawa S, Prall OW, Harvey RP, Fukuda K Rationale: The transcriptional networks guiding heart development remain poorly understood, despite the identification of several essential cardiac transcription factors. Objective: To isolate novel cardiac transcription factors, we performed gene chip analysis and found that Zac1, a zinc finger-type transcription factor, was strongly expressed in the developing heart. This study was designed to investigate the molecular and functional role of Zac1 as a cardiac transcription factor. Methods and Results: Zac1 was strongly expressed in the heart from cardiac crescent stages and in the looping heart showed a chamber-restricted pattern. Zac1 stimulated luciferase reporter constructs driven by ANF, BNP, or alphaMHC promoters. Strong functional synergy was seen between Zac1 and Nkx2-5 on the ANF promoter, which carries adjacent Zac1 and Nkx2-5 DNA-binding sites. Zac1 directly associated with the ANF promoter in vitro and in vivo, and Zac1 and Nkx2-5 physically associate! d through zinc fingers 5 and 6 in Zac1, and the homeodomain in Nkx2-5. Zac1 is a maternally imprinted gene and is the first such gene found to be involved in heart development. Homozygous and paternally derived heterozygous mice carrying an interruption in the Zac1 locus showed decreased levels of chamber and myofilament genes, increased apoptotic cells, partially penetrant lethality and morphological defects including atrial and ventricular septal defects, and thin ventricular walls. Conclusions: Zac1 plays an essential role in the cardiac gene regulatory network. Our data provide a potential mechanistic link between Zac1 in cardiogenesis and congenital heart disease manifestations associated with genetic or epigenetic defects in an imprinted gene network. PMID: 20167925 [PubMed - as supplied by publisher] | | | | 
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