| Targeting aldehyde dehydrogenase: a potential approach for cell labeling.
October 31, 2009 at 8:09 am
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| | Targeting aldehyde dehydrogenase: a potential approach for cell labeling. Nucl Med Biol. 2009 Nov;36(8):919-29 Authors: Vaidyanathan G, Song H, Affleck D, McDougald DL, Storms RW, Zalutsky MR, Chin BB INTRODUCTION: To advance the science and clinical application of stem cell therapy, the availability of a highly sensitive, quantitative and translational method for tracking stem cells would be invaluable. Because hematopoetic stem cells express high levels of the cytosolic enzyme aldehyde dehydrogenase-1A1 (ALDH1), we sought to develop an agent that is specific to ALDH1 and thus to cells expressing the enzyme. Such an agent might be also helpful in identifying tumors that are resistant to cyclophosphomide chemotherapy because ALDH1 is known to be responsible for this resistance. METHODS: We developed schemes for the synthesis of two radioiodinated aldehdyes - N-formylmethyl-5-[*I]iodopyridine-3-carboxamide ([*I]FMIC) and 4-diethylamino-3-[*I]iodobenzaldehyde ([*I]DEIBA)-at no-carrier-added levels from their respective tin precursors. These agents were evaluated using pure ALDH1 and tumor cells that expressed the enzyme. RESULTS: The average radiochemical yields for the synthesis of [(125)I]FMIC and [(125)I]DEIBA were 70+/-5% and 47+/-14%, respectively. ALDH1 converted both compounds to respective acids suggesting their suitability as ALDH1 imaging agents. Although ability of ALDH1 within the cells to oxidize one of these substrates was shown, specific uptake in ALDH-expressing tumor cells could not be demonstrated. CONCLUSION: To pursue this approach for ALDH1 imaging, radiolabeled aldehydes need to be designed such that, in addition to being good substrates for ALDH1, the cognate products should be sufficiently polar so as to be retained within the cells. PMID: 19875048 [PubMed - in process] |
| VEGF Induces Differentiation of Functional Endothelium From Human Embryonic Stem Cells. Implications for Tissue Engineering.
October 31, 2009 at 6:58 am
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| | VEGF Induces Differentiation of Functional Endothelium From Human Embryonic Stem Cells. Implications for Tissue Engineering. Arterioscler Thromb Vasc Biol. 2009 Oct 29; Authors: Nourse MB, Halpin DE, Scatena M, Mortisen DJ, Tulloch NL, Hauch KD, Torok-Storb B, Ratner BD, Pabon L, Murry CE OBJECTIVE: Human embryonic stem cells (hESCs) offer a sustainable source of endothelial cells for therapeutic vascularization and tissue engineering, but current techniques for generating these cells remain inefficient. We endeavored to induce and isolate functional endothelial cells from differentiating hESCs. METHODS AND RESULTS: To enhance endothelial cell differentiation above a baseline of approximately 2% in embryoid body (EB) spontaneous differentiation, 3 alternate culture conditions were compared. Vascular endothelial growth factor (VEGF) treatment of EBs showed the best induction, with markedly increased expression of endothelial cell proteins CD31, VE-Cadherin, and von Willebrand Factor, but not the hematopoietic cell marker CD45. CD31 expression peaked around days 10 to 14. Continuous VEGF treatment resulted in a 4- to 5-fold enrichment of CD31(+) cells but did not increase endothelial proliferation rates, suggesting a primary effect on differentiation. CD31(+) cells purified from differentiating EBs upregulated ICAM-1 and VCAM-1 in response to TNFalpha, confirming their ability to function as endothelial cells. These cells also expressed multiple endothelial genes and formed lumenized vessels when seeded onto porous poly(2-hydroxyethyl methacrylate) scaffolds and implanted in vivo subcutaneously in athymic rats. Collagen gel constructs containing hESC-derived endothelial cells and implanted into infarcted nude rat hearts formed robust networks of patent vessels filled with host blood cells. CONCLUSIONS: VEGF induces functional endothelial cells from hESCs independent of endothelial cell proliferation. These enrichment methods increase endothelial cell yield, enabling applications for revascularization as well as basic studies of human endothelial biology. We demonstrate the ability of hESC-derived endothelial cells to facilitate vascularization of tissue-engineered implants. PMID: 19875721 [PubMed - as supplied by publisher] |
| Biocompatibility, alignment degree and mechanical properties of an electrospun chitosan-P(LLA-CL) fibrous scaffold.
October 31, 2009 at 6:58 am
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| | Biocompatibility, alignment degree and mechanical properties of an electrospun chitosan-P(LLA-CL) fibrous scaffold. J Biomater Sci Polym Ed. 2009;20(14):2117-28 Authors: Chen F, Su Y, Mo X, He C, Wang H, Ikada Y Chitosan-poly(L-lactide-co-epsilon-caprolactone) (P(LLA-CL)) complex fibers, fibrous mats and a tubular scaffold have been obtained through electrospinning. Due to their high porosity, there were more porcine iliac artery endothelial cells (PIECs) attached to fiber mats than to tissue-culture plate (TCP) and coverslips. The cells could grow and spread well on nanofiber mats. There were many of native extracellular matrix (ECM)-like colloids above and under the surface of fibrous mats after cell culturing. The two-dimensional fast Fourier transform (2-D FFT) approach was used to analysis alignment degree of fibers collected on a rotary mandrel. The relations among mechanical properties, alignment degree, fiber diameter and rotary speed are discussed. Aligned fibers with various alignment degrees could be found through adjusting rotary speed. Fiber alignment was the variable most closely associated with the regulation of stress and strain. In this study, we show a feasible approach for producing scaffold with controllable mechanical property for soft tissue engineering through electrospinning. PMID: 19874681 [PubMed - in process] |
| Fabrication of nano-fibrous PLLA scaffold reinforced with chitosan fibers.
October 31, 2009 at 6:58 am
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| | Fabrication of nano-fibrous PLLA scaffold reinforced with chitosan fibers. J Biomater Sci Polym Ed. 2009;20(14):1995-2002 Authors: Wang X, Song G, Lou T, Peng W In this study, a nano-fibrous PLLA scaffold reinforced by micro-scale chitosan fibers was fabricated using thermally-induced phase separation (TIPS). The morphology, porosity, mechanical performance and pH changes in in vitro degradation of the scaffold were also investigated. Results showed that the mechanical properties of the scaffold increased with the amount of chitosan fibers embedded, and the pH in in vitro degradation of the scaffold changed more slowly than that of the pure nano-fibrous PLLA scaffold without chitosan fibers. The new composite scaffold might be a very promising scaffold for tissue engineering. PMID: 19874673 [PubMed - in process] |
| Comparison of bone marrow stromal cell behaviors on poly(caprolactone) with or without surface modification: studies on cell adhesion, survival and proliferation.
October 31, 2009 at 6:58 am
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| | Comparison of bone marrow stromal cell behaviors on poly(caprolactone) with or without surface modification: studies on cell adhesion, survival and proliferation. J Biomater Sci Polym Ed. 2009;20(14):1975-93 Authors: Zhang H, Hollister S Poly(caprolactone) (PCL) is a promising biodegradable polymer for tissue engineering. However, intrinsically poor cell-adhesive properties of PCL may limit its application. In this study, the PCL film surface was modified with RGDC peptide by a chemical immobilization procedure. Furthermore, bone marrow stromal cell (BMSC) behaviors including attachment, spreading, focal adhesion formation, focal adhesion kinase (FAK) activation, apoptosis and proliferation when cultured on the modified PCL films were investigated. Our results demonstrated that PCL with RGD modification promoted initial BMSC attachment, spreading and focal adhesion formation. At a later time point (12 h), BMSC attachment on both RGD peptide-modified PCL and PCL-NH(2) films significantly increased compared to untreated PCL films. Importantly, FAK phosphorylation was significantly increased only on the films with RGD-modified films, not on the PCL-NH(2) films, demonstrating that PCL with RGD modification had an advantage in initiating the specific integrin-mediated signal transduction and might play an important role in the subsequent retardation in cell death and enhancement in cell proliferation. The present results provide more evidence that functionalizing PCL with RGD peptides may be a feasible way to improve the interaction between BMSC and PCL substrate, which is important in tissue engineering. PMID: 19874672 [PubMed - in process] |
| Not a process of simple vicariousness, the differentiation of human adipose-derived mesenchymal stem cells to renal tubular epithelial cells plays an important role in acute kidney injury repairing.
October 31, 2009 at 6:58 am
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| | Not a process of simple vicariousness, the differentiation of human adipose-derived mesenchymal stem cells to renal tubular epithelial cells plays an important role in acute kidney injury repairing. Stem Cells Dev. 2009 Oct 29; Authors: Li K, Han Q, Yan X, Liao L, Zhao RC The recent findings indicate that under conditions of severe tubular injuries, transplantation of mesenchymal stem cells (MSCs) may comprise a promising treatment in acute kidney diseases; nevertheless, the underling mechanism is still under debate. To investigate the differentiation characteristics and the role of MSCs in renal tubular injury, human adipose-derived MSCs (hAD-MSCs) were transplanted into ischemia-reperfusion (I/R) kidneys in C57BL/6 mouse model. Results showed that hAD-MSCs were able to differentiate toward renal tubular epithelium at early stage of injuries. The differentiated donor cells replaced the vacant space left over by the dead cells, contributed to maintenance of structural integrity and proceeding to subsequent tissue repair process. Furthermore, MSCs as supportive cells may promote repair via secreting cytokines. The differentiation and replacement of MSCs at extremely early stage play important roles for the subsequent self-repair and renewal of functional cells. Direct differentiation of MSCs, as an important mechanism of injured kidney repair, warrants further investigation. PMID: 19874085 [PubMed - as supplied by publisher] |
| Cellular cardiac regenerative therapy in which patients?
October 31, 2009 at 6:58 am
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| | Cellular cardiac regenerative therapy in which patients? Expert Rev Cardiovasc Ther. 2009 Aug;7(8):911-9 Authors: Chachques JC Cell-based myocardial regenerative therapy is undergoing experimental and clinical trials in order to limit the consequences of decreased contractile function and compliance of damaged ventricles owing to ischemic and nonischemic myocardial diseases. A variety of myogenic and angiogenic cell types have been proposed, such as skeletal myoblasts, mononuclear and mesenchymal bone marrow cells, circulating blood-derived progenitors, adipose-derived stromal cells, induced pluripotent stem cells, umbilical cord cells, endometrial mesenchymal stem cells, adult testis pluripotent stem cells and embryonic cells. Current indications for stem cell therapy concern patients who have had a left- or right-ventricular infarction or idiopathic dilated cardiomyopathies. Other indications and potential applications include patients with diabetic cardiomyopathy, Chagas heart disease (American trypanosomiasis), ischemic mitral regurgitation, left ventricular noncompacted myocardium and pediatric cardiomyopathy. Suitable sources of cells for cardiac implant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful. It is important to note that stem cells are not an alternative to heart transplantation; selected patients should be in an early stage of heart failure as the goal of this regenerative approach is to avoid or delay organ transplantation. Since the cell niche provides crucial support needed for stem cell maintenance, the most interesting and realistic perspectives include the association of intramyocardial cell transplantation with tissue-engineered scaffolds and multisite cardiac pacing in order to transform a passive regenerative approach into a 'dynamic cellular support', a promising method for the creation of 'bioartificial myocardium'. PMID: 19673669 [PubMed - indexed for MEDLINE] |
| Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation.
October 31, 2009 at 3:42 am
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| | Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature. 2009 Oct 28; Authors: Kee K, Angeles VT, Flores M, Nguyen HN, Reijo Pera RA The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages. Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications. PMID: 19865085 [PubMed - as supplied by publisher] |
| Regenerative medicine: advances in new methods and technologies.
October 31, 2009 at 3:42 am
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| | Regenerative medicine: advances in new methods and technologies. Med Sci Monit. 2009 Nov;15(11):RA233-51 Authors: Park DH, Eve DJ The articles published in the journal Cell Transplantation - The Regenerative Medicine Journal over the last two years reveal the recent and future cutting-edge research in the fields of regenerative and transplantation medicine. 437 articles were published from 2007 to 2008, a 17% increase compared to the 373 articles in 2006-2007. Neuroscience was still the most common section in both the number of articles and the percentage of all manuscripts published. The increasing interest and rapid advance in bioengineering technology is highlighted by tissue engineering and bioartificial organs being ranked second again. For a similar reason, the methods and new technologies section increased significantly compared to the last period. Articles focusing on the transplantation of stem cell lineages encompassed almost 20% of all articles published. By contrast, the non-stem cell transplantation group which is made up primarily of islet cells, followed by biomaterials and fetal neural tissue, etc. comprised less than 15%. Transplantation of cells pre-treated with medicine or gene transfection to prolong graft survival or promote differentiation into the needed phenotype, was prevalent in the transplantation articles regardless of the kind of cells used. Meanwhile, the majority of non-transplantation-based articles were related to new devices for various purposes, characterization of unknown cells, medicines, cell preparation and/or optimization for transplantation (e.g. isolation and culture), and disease pathology.<br /> PMID: 19865067 [PubMed - in process] | 
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