| 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
|
| | 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
|
| | 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
|
| | 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
|
| | 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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| Generation of functional human hepatic endoderm from human induced pluripotent stem cells.
October 31, 2009 at 6:01 am
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| | Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology. 2009 Sep 29; Authors: Sullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross JA, Samuel K, Wang G, Daley GQ, Lee JH, Church GM, Forbes SJ, Iredale JP, Wilmut I With the advent of induced pluripotent stem cell (iPSC) technology, it is now feasible to generate iPSCs with a defined genotype or disease state. When coupled with direct differentiation to a defined lineage, such as hepatic endoderm (HE), iPSCs would revolutionize the way we study human liver biology and generate efficient "off the shelf" models of human liver disease. Here, we show the "proof of concept" that iPSC lines representing both male and female sexes and two ethnic origins can be differentiated to HE at efficiencies of between 70%-90%, using a method mimicking physiological relevant condition. The iPSC-derived HE exhibited hepatic morphology and expressed the hepatic markers albumin and E-cadherin, as assessed by immunohistochemistry. They also expressed alpha-fetoprotein, hepatocyte nuclear factor-4a, and a metabolic marker, cytochrome P450 7A1 (Cyp7A1), demonstrating a definitive endodermal lineage differentiation. Furthermore, iPSC-derived hepatocytes produced and secreted the plasma proteins, fibrinogen, fibronectin, transthyretin, and alpha-fetoprotein, an essential feature for functional HE. Additionally iPSC-derived HE supported both CYP1A2 and CYP3A4 metabolism, which is essential for drug and toxicology testing. Conclusion: This work is first to demonstrate the efficient generation of hepatic endodermal lineage from human iPSCs that exhibits key attributes of hepatocytes, and the potential application of iPSC-derived HE in studying human liver biology. In particular, iPSCs from individuals representing highly polymorphic variants in metabolic genes and different ethnic groups will provide pharmaceutical development and toxicology studies a unique opportunity to revolutionize predictive drug toxicology assays and allow the creation of in vitro hepatic disease models. (HEPATOLOGY 2009.). PMID: 19877180 [PubMed - as supplied by publisher] |
| Genome modification in human embryonic stem cells.
October 31, 2009 at 6:01 am
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| | Genome modification in human embryonic stem cells. J Cell Physiol. 2009 Oct 28; Authors: Tenzen T, Zembowicz F, Cowan CA Induced pluripotent stem cell (iPSC) technology has emerged as the most promising method for generating patient-specific human embryonic stem (ES) cells and adult stem cells (Takahashi et al., 2007, Cell 131:861-872; Wernig et al., 2007, Nature 448:318-324; Park et al., 2008, Nature 451:141-146). So far, most studies of direct reprogramming have been done by using lentiviruses/retroviruses encoding the reprogramming factors. This represents a major limitation to therapeutic applications since viral integration in the host genome increases the risk of tumorigenicity, and low-level residual expression of reprogramming factors may alter the differentiation potential of the human iPSCs (hiPSCs). As a result, more attention has been paid to developing new techniques to manipulate the human genome, with the goal of making safer hiPSCs that have fewer or no lesions or alterations in the genome. Additionally, the efficiency of reprogramming and of homologous recombination in gene therapy must be improved, if iPSC technology is to be a viable tool in regenerative medicine. Here, we summarize the recent developments in human genome manipulation for generating hiPSCs and advances in homologous recombination for gene targeting. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc. PMID: 19877154 [PubMed - as supplied by publisher] |
| Inpp5f Is a Polyphosphoinositide Phosphatase That Regulates Cardiac Hypertrophic Responsiveness.
October 31, 2009 at 6:01 am
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| | Inpp5f Is a Polyphosphoinositide Phosphatase That Regulates Cardiac Hypertrophic Responsiveness. Circ Res. 2009 Oct 29; Authors: Zhu W, Trivedi CM, Zhou D, Yuan L, Lu MM, Epstein JA Rationale: Cardiac hypertrophy occurs in response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. The phosphatidylinositol 3-kinase/Akt pathway has previously been strongly associated with hypertrophic signaling in the heart, and with the control of cell size in multiple contexts. This pathway is tightly regulated by many factors, including a host of kinases and phosphatases that function at multiple steps in the signaling cascade. For example, the PTEN (phosphatase and tensin homolog) tumor suppressor protein is a phosphoinositide 3-phosphatase that, by metabolizing PtdIns(3,4,5)P3, acts in direct antagonism to growth factor-stimulated phosphatidylinositol 3-kinase. Inhibition of PTEN leads to cardiomyocyte hypertrophy. Another polyphoinositide phosphatase, inositol polyphosphate-5-phosphatase F (Inpp5f) has recently been implicated in regulation of cardiac hypertrophy. Like PTEN, this phosphatase can degrade PtdIns(3,4,5)P3 and thus modulates the phosphatidylinositol 3-kinase/Akt pathway. Objective: To characterize the role of Inpp5f in regulating cardiac hypertrophy. Methods and Results: We generated homozygous Inpp5f knockout mice and cardiac specific Inpp5f overexpression transgenic mice. We evaluated their hearts for biochemical, structural and functional changes. Inpp5f knockout mice have augmented hypertrophy and reactivation of the fetal gene program in response to stress when compared to wild-type littermates. Furthermore, cardiac overexpression of Inpp5f in transgenic mice reduces hypertrophic responsiveness. Conclusions: Our results suggest that Inpp5f is a functionally important endogenous modulator of cardiac myocyte size and of the cardiac response to stress. PMID: 19875726 [PubMed - as supplied by publisher] |
| VEGF Induces Differentiation of Functional Endothelium From Human Embryonic Stem Cells. Implications for Tissue Engineering.
October 31, 2009 at 6:01 am
|
| | 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] |
| Targeting aldehyde dehydrogenase: a potential approach for cell labeling.
October 31, 2009 at 6:01 am
|
| | 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] |
| Biocompatibility, alignment degree and mechanical properties of an electrospun chitosan-P(LLA-CL) fibrous scaffold.
October 31, 2009 at 6:01 am
|
| | 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 6:01 am
|
| | 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 6:01 am
|
| | 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 6:01 am
|
| | 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] |
| Restoration of Runx1 expression in the Tie2 cell compartment rescues definitive hematopoietic stem cells and extends life of Runx1 knockout animals until birth.
October 31, 2009 at 6:01 am
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| | Restoration of Runx1 expression in the Tie2 cell compartment rescues definitive hematopoietic stem cells and extends life of Runx1 knockout animals until birth. Stem Cells. 2009 Jul;27(7):1616-24 Authors: Liakhovitskaia A, Gribi R, Stamateris E, Villain G, Jaffredo T, Wilkie R, Gilchrist D, Yang J, Ure J, Medvinsky A Mice deficient in the runt homology domain transcription factor Runx1/AML1 fail to generate functional clonogenic hematopoietic cells and die in utero by embryonic day 12.5. We previously generated Runx1 reversible knockout mice, in which the Runx1 locus can be restored by Cre-mediated recombination. We show here that selective restoration of the Runx1 locus in the Tie2 cell compartment rescues clonogenic hematopoietic progenitors in early Runx1-null embryos and rescues lymphoid and myeloid lineages during fetal development. Furthermore, fetal liver cells isolated from reactivated Runx1 embryos are capable of long-term multilineage lymphomyeloid reconstitution of adult irradiated recipients, demonstrating the rescue of definitive hematopoietic stem cells. However, this rescue of the definitive hematopoietic hierarchy is not sufficient to rescue the viability of animals beyond birth, pointing to an essential role for Runx1 in other vital developmental processes. PMID: 19544462 [PubMed - indexed for MEDLINE] | | | 
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| Correction
October 30, 2009 at 6:06 pm
|
| | The "Loan" item on Oct. 29, 2009, misspelled the last name of Alex Lash as Kash. |
| Thermogenesis Corp. to Announce First Quarter Fiscal 2010 Results on November 5, 2009
October 30, 2009 at 5:03 pm
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| Immunotherapy demonstrates long-term success in treating lymphoma
October 30, 2009 at 4:03 pm
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| GREENBioPharma -- Dec. 2-3, 2009
October 30, 2009 at 12:00 pm
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| Reduction of Neu5GC Xenoantigen on Human ADSC/MSCs lead to Them as Safer and More Useful Cell Sources for Realizing Various Stem Cell Therapies.
October 30, 2009 at 11:08 am
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| | Reduction of Neu5GC Xenoantigen on Human ADSC/MSCs lead to Them as Safer and More Useful Cell Sources for Realizing Various Stem Cell Therapies. Tissue Eng Part A. 2009 Oct 28; Authors: Komoda H, Okura H, Lee CM, Sougawa N, Iwayama T, Hashikawa T, Saga A, Yamamoto A, Ichinose A, Murakami S, Sawa Y, Matsuyama A Adipose tissue is an attractive source for somatic stem cell therapy. Currently, human ADSC/MSCs are usually cultured with fetal bovine serum (FBS). Recently, however, not only human embryonic stem cell lines cultured on mouse feeder cells but also bone marrow derived hMSCs cultured with FBS were reported to express N-glycolylneuraminic acid (Neu5Gc) xenoantigen. Human serum contains high titers of natural preformed antibodies against Neu5Gc. We studied the presence of Neu5Gc on hADSC/MSCs cultured with FBS and human immune response mediated by Neu5Gc. Our data indicated that hADSC/MSCs cultured with FBS expressed Neu5Gc and human natural preformed antibodies could bind to hADSC/MSCs. However, hADSC/MSCs express complement regulatory proteins such as CD46, CD55, and CD59 and is largely resistant to complement-mediated cytotoxity (CMC). hADSC/MSCs cultured with FBS could be injured by antibody dependent cell-mediated cytotoxicity (ADCC) mechanism. Furthermore, human monocyte derived macrophages could phagocytose hADSC/MSCs cultured with FBS and this phagocytosis activity increased in the presence of human serum. Culturing the hADSC/MSCs with heat-inactivated human serum for a week could markedly reduce Neu5Gc on hADSC/MSCs and prevented immune responses mediated by Neu5Gc, such as human natural preformed antibodies binding, ADCC, and phagocytosis. Adipogenic and osteogenic differentiation potential of hADSC/MSCs cultured with heat-inactivated human serum was not less than those cultured with FBS. For stem cell therapies based on hADSC/MSCs to be realized, hADSC/MSCs that presented Neu5Gc on their cell surfaces after exposure to FBS should be clean up to be rescued from xenogenic rejection. PMID: 19863253 [PubMed - as supplied by publisher] |
| Regenerative medicine: Advances in new methods and technologies.
October 30, 2009 at 6:46 am
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| | Regenerative medicine: Advances in new methods and technologies. Med Sci Monit. 2009 Nov;15(11):RA233-251 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] |
| Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds.
October 30, 2009 at 6:46 am
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| | Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. J R Soc Interface. 2009 Oct 28; Authors: Mouriño V, Boccaccini AR This paper provides an extensive overview of published studies on the development and applications of three-dimensional bone tissue engineering (TE) scaffolds with potential capability for the controlled delivery of therapeutic drugs. Typical drugs considered include gentamicin and other antibiotics generally used to combat osteomyelitis, as well as anti-inflammatory drugs and bisphosphonates, but delivery of growth factors is not covered in this review. In each case reviewed, special attention has been given to the technology used for controlling the release of the loaded drugs. The possibility of designing multifunctional three-dimensional bone TE scaffolds for the emerging field of bone TE therapeutics is discussed. A detailed summary of drugs included in three-dimensional scaffolds and the several approaches developed to combine bioceramics with various polymeric biomaterials in composites for drug-delivery systems is included. The main results presented in the literature are discussed and the remaining challenges in the field are summarized with suggestions for future research directions. PMID: 19864265 [PubMed - as supplied by publisher] |
| Direct contribution of axial impact compressive load to anterior tibial load during simulated ski landing impact.
October 30, 2009 at 6:46 am
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| | Direct contribution of axial impact compressive load to anterior tibial load during simulated ski landing impact. J Biomech. 2009 Oct 26; Authors: Yeow CH, Lee PV, Goh JC Anterior tibial loading is a major factor involved in the anterior cruciate ligament (ACL) injury mechanism during ski impact landing. We sought to investigate the direct contribution of axial impact compressive load to anterior tibial load during simulated ski landing impact of intact knee joints without quadriceps activation. Twelve porcine knee specimens were procured. Four specimens were used as non-impact control while the remaining eight were mounted onto a material-testing system at 70 degrees flexion and subjected to simulated landing impact, which was successively repeated with incremental actuator displacement. Four specimens from the impacted group underwent pre-impact MRI for tibial plateau angle measurements while the other four were subjected to histology and microCT for cartilage morphology and volume assessment. The tibial plateau angles ranged from 29.4 to 38.8 degrees . There was a moderate linear relationship (Y=0.16X; R(2)=0.64; p<0.001) between peak axial impact compressive load (Y) and peak anterior tibial load (X). The anterior and posterior regions in the impacted group sustained surface cartilage fraying, superficial clefts and tidemark disruption, compared to the control group. MicroCT scans displayed visible cartilage deformation for both anterior and posterior regions in the impacted group. Due to the tibial plateau angle, increased axial impact compressive load can directly elevate anterior tibial load and hence contribute to ACL failure during simulated landing impact. Axial impact compressive load resulted in shear cartilage damage along anterior-posterior tibial plateau regions, due to its contribution to anterior tibial loading. This mechanism plays an important role in elevating ACL stress and cartilage deformation during impact landing. PMID: 19863961 [PubMed - as supplied by publisher] |
| Peyronie's Surgery: Graft Choices and Outcomes.
October 30, 2009 at 6:46 am
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| | Peyronie's Surgery: Graft Choices and Outcomes. Curr Urol Rep. 2009 Nov;10(6):460-7 Authors: Lentz AC, Carson Iii CC Peyronie's disease (PD), a localized fibrosis of the tunica albuginea surrounding the penile corpora, results in penile curvature and sexual dysfunction. Men with significant penile curvature and satisfactory erectile function are often treated with plaque incision or excision and grafting. The advantages and disadvantages of various grafting materials have long been debated. Graft materials can be divided into three categories: autologous tissue harvested from the patient's body, allograft or xenograft from another person or species, and synthetic grafts. Despite groundbreaking advances in physiology, synthetic materials, and tissue engineering, the ideal graft material has yet to be established. This review presents and discusses the variety of graft materials available for the surgical correction of PD. For this purpose, a MEDLINE search was conducted on PD until May 2009. PMID: 19863858 [PubMed - in process] |
| Histochemical analyses of tissue-engineered human menisci.
October 30, 2009 at 6:46 am
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| | Histochemical analyses of tissue-engineered human menisci. Connect Tissue Res. 2009;50(5):307-14 Authors: Schoenfeld AJ, Jacquet R, Lowder E, Doherty A, Leeson MC, Landis WJ The field of tissue engineering remains one of the least explored areas of current meniscal research but holds great promise. In this investigation, meniscal fibrochondrocytes were isolated from fresh human meniscal tissue and seeded onto synthetic polyglycolic acid (PGA) scaffolds. Constructs were implanted into the dorsal subcutaneous space of athymic nude mice. Control scaffolds, devoid of meniscal cells, were simultaneously implanted in additional mice. Constructs were harvested over 12 weeks and treated with a variety of histochemical stains to analyze general specimen morphology, cellular viability and proliferation, and collagen secretion. Results indicate that meniscal fibrochondrocyte proliferation increased over the time of implantation with cellular consolidation occurring as the PGA scaffolding was progressively hydrolyzed. Collagen production also increased over time. There were favorable similarities between constructs and human meniscal controls in terms of cellular morphology, phenotypic expression, and collagen production. These initial findings demonstrate procedures supporting proliferation of meniscal fibrochondrocytes, expression of fibrochondral phenotype, and the formation of putative meniscal tissue. PMID: 19863389 [PubMed - in process] |
| The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model.
October 30, 2009 at 6:46 am
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| | The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model. Tissue Eng Part A. 2009 Oct 28; Authors: Ho ST, Hutmacher DW, Ekaputra AK, Hitendra D, James HH Conventional clinical therapies are unable to resolve osteochondral defects adequately, hence tissue engineering solutions are sought to address the challenge. A biphasic implant which was seeded with Mesenchymal Stem Cells (MSC) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a Polycaprolactone (PCL) cartilage scaffold and a Polycaprolactone - Tri Calcium Phosphate (PCL - TCP) osseous matrix. Autologous MSC was seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL - collagen electrospun mesh that served as a substitute for periosteal flap in preventing cell leakage. Controls either without implanted MSC or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by the superior Glycosaminoglycan (GAG) maintenance. This positive morphological outcome was supported by a higher relative Young's modulus which indicated functional cartilage restoration. Bone in growth and remodeling occurred in all groups with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover healing was inferior at the patellar groove as compared to the medial condyle and this was attributed to the native biomechanical features. PMID: 19863255 [PubMed - as supplied by publisher] |
| Skin and bones (and cartilage): the dermal fibroblast connection.
October 30, 2009 at 6:46 am
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| | Skin and bones (and cartilage): the dermal fibroblast connection. Nat Rev Rheumatol. 2009 Sep;5(9):471-2 Authors: Tuan RS PMID: 19710666 [PubMed - indexed for MEDLINE] |
| The ideal graft of the future: a prospect of messianic proportions?
October 30, 2009 at 6:46 am
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| | The ideal graft of the future: a prospect of messianic proportions? Asian Cardiovasc Thorac Ann. 2009 Jun;17(3):238-9 Authors: Klima U, Kofidis T PMID: 19643845 [PubMed - indexed for MEDLINE] |
| Vitreous cryopreservation of tissue engineered bone composed of bone marrow mesenchymal stem cells and partially demineralized bone matrix.
October 30, 2009 at 6:46 am
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| | Vitreous cryopreservation of tissue engineered bone composed of bone marrow mesenchymal stem cells and partially demineralized bone matrix. Cryobiology. 2009 Oct;59(2):180-7 Authors: Yin H, Cui L, Liu G, Cen L, Cao Y Cryopreservation of tissue engineered products by maintaining their structure and function is a prerequisite for large-scale clinical applications. In this study, we examined the feasibility of cryopreservation of tissue engineered bone (TEB) composed of osteo-induced canine bone marrow mesenchymal stem cells (cBMSCs) and partially demineralized bone matrix (pDBM) scaffold by vitrification. A novel vitreous solution named as VS442 containing 40% dimethyl-sulfoxide (DMSO), 40% EuroCollins (EC) solution and 20% basic culture medium (BCM) was developed. After being cultured in vitro for 8 days, cell/scaffold complex in VS442 was subjected to vitreous preservation for 7 days and 3 months, respectively. Cell viability, proliferation and osteogenic differentiation of cBMSCs in TEB after vitreous cryopreservation were examined with parallel comparisons being made with those cryopreserved in VS55 vitreous solution. Compared with that cryopreserved in VS55, cell viability and subsequent proliferative ability of TEB in VS442 after being rewarmed were significantly higher as detected by live/dead staining and DNA assay. The level of alkaline phosphatase (ALP) expression and osteocalcin (OCN) deposition in VS442 preserved TEB was also higher than those in the VS55 group since 3days post-rewarm. Both cell viability and osteogenic capability of the VS55 group were found to be declined to a negligible level within 15 days post-rewarm. Furthermore, it was observed that extending the preservation of TEB in VS442 to 3 months did not render any significant effect on its survival and osteogenic potential. Thus, the newly developed VS442 vitreous solution was demonstrated to be more efficient in maintaining cellular viability and osteogenic function for vitreous cryopreservation of TEB over VS55. PMID: 19576196 [PubMed - indexed for MEDLINE] |
| Ex vivo functional evaluation of isolated strips in BAMG tissue-engineered bladders.
October 30, 2009 at 6:46 am
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| | Ex vivo functional evaluation of isolated strips in BAMG tissue-engineered bladders. Int J Artif Organs. 2009 Mar;32(3):159-65 Authors: Chen BS, Zhang SL, Geng H, Pan J, Chen F Although gastrointestinal segments have been widely used for bladder augmentation, they are still not considered ideal sources due to the possibility of complications. In this study, with the aim of reducing complications, we performed bladder augmentation in pigs using bladder acellular matrix grafts (BAMG) as a scaffold. Three months after surgery, the BAMG tissue-engineered bladders revealed bladder reconstruction that morphologically resembled that of the normal bladder. Functional experiments were performed to evaluate the contractile characteristics of isolated strips from both normal and BAMG tissue-engineered bladders 3 months after augmentation. No significant differences between these two groups were found in spontaneous contraction and contraction after electric stimulation; in the relaxing effect of epinephrine on potassium chloride-induced twitch height; in the contracting effects of acetylcholin; or in the antagonistic effect of atropine on acetylcholine-induced contraction. These results demonstrate that not only can BAMG tissue-engineered bladders be histologically reconstructed, they also possess electrophysiological and pharmacological characteristics similar to normal bladders. This further confirms BAMG as an ideal scaffold for bladder augmentation. PMID: 19440991 [PubMed - indexed for MEDLINE] |
| [Use of allogenic acellular dermal matrix combined with autologous epidermal cells for the repair of tissue defect]
October 30, 2009 at 6:46 am
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| | [Use of allogenic acellular dermal matrix combined with autologous epidermal cells for the repair of tissue defect] Zhonghua Kou Qiang Yi Xue Za Zhi. 2005 Sep;40(5):412-5 Authors: Zuo JH, Li JR, Li WX, Yang YC, Wu SH, Lü ZH OBJECTIVE: To investigate a method for the repair of tissue defect. METHODS: Allogenic acellular dermal matrixes (ADM) were implanted to full-thickness skin defects made on the dorsa of rats. Two weeks later, autologous suspended epidermal cells were transplanted on to the surface of vascularized ADM. Respectively, neoepidermis was macroscopically observed 2, 3, 5 weeks after grafting, and samples were taken to make routine paraffin sections for microscopical examination, and immunohistochemical staining for type IV collagen was also performed. RESULTS: The vascularized ADM could support proliferation and differentiation of epidermal cells, and also could promote the formation of dermal-epidermal junction. Suspended epidermal cells in an artificial culture system in vivo could develop into mature epidermis. The reconstructed skin not only looked like the normal one in appearance in which hair was removed, but also revealed a better function. CONCLUSIONS: Full-thickness skin defect can be repaired by transplanting autologous epidermal cell suspension on to vascularized ADM. PMID: 16255932 [PubMed - indexed for MEDLINE] |
| [Experimental study of tissue engineered bone loaded with osteointergrated dental implants]
October 30, 2009 at 6:46 am
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| | [Experimental study of tissue engineered bone loaded with osteointergrated dental implants] Zhonghua Kou Qiang Yi Xue Za Zhi. 2005 Jul;40(4):323-6 Authors: Fu SJ, Wang YX, Chen FL, Tao K, Zhang XD, Ge C OBJECTIVE: To investigate osteogenesis and integration of osteointergrated dental implants with marrow stromal osteoblast and cancellous bone matrix compound artificial bone (MCCAB) when embedded subcutaneously. METHODS: Osteointergrated dental implants (3 mm in diameter) were inserted into cancellous bone matrix (CBM) columns (5 mm in diameter). Marrow stromal osteoblast (MSO) were cultured and expanded in the column and on the surface. The osteointergrated dental implants loaded MSO-Alginate-CBM compound was formatted. This compound was then implanted subcutaneously in nude mice, and the osteointergrated dental implants loaded Alginate-CBM compounds were implanted as control. The compound was in the mice for 4 to 8 weeks and then harvested and assessed by means of gross observation, X-ray examination, histologic observation and computerized histomorphometry for evaluation of bone formation. RESULTS: The osteogenesis of the osteointergrated dental implants loaded MSO-Alginate-CBM compound was better than that of the the osteointergrated dental implants loaded Alginate-CBM compound. Both intramembranous and cartilaginous osteogenesis was seen but the former was predominant. A large amount of new bone formed around the implant and integrated well with the implant. In the control, only slight cartilage osteogenesis was seen and no integration was found. CONCLUSIONS: The results suggest that the new bone forms in the scaffolds and on the surface of the implant, and integration between the implant and artificial bone also occurs when they are implanted in the nude mice. PMID: 16191379 [PubMed - indexed for MEDLINE] |
| Reduction of Neu5GC Xenoantigen on Human ADSC/MSCs lead to Them as Safer and More Useful Cell Sources for Realizing Various Stem Cell Therapies.
October 30, 2009 at 6:17 am
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| | Reduction of Neu5GC Xenoantigen on Human ADSC/MSCs lead to Them as Safer and More Useful Cell Sources for Realizing Various Stem Cell Therapies. Tissue Eng Part A. 2009 Oct 28; Authors: Komoda H, Okura H, Lee CM, Sougawa N, Iwayama T, Hashikawa T, Saga A, Yamamoto A, Ichinose A, Murakami S, Sawa Y, Matsuyama A Adipose tissue is an attractive source for somatic stem cell therapy. Currently, human ADSC/MSCs are usually cultured with fetal bovine serum (FBS). Recently, however, not only human embryonic stem cell lines cultured on mouse feeder cells but also bone marrow derived hMSCs cultured with FBS were reported to express N-glycolylneuraminic acid (Neu5Gc) xenoantigen. Human serum contains high titers of natural preformed antibodies against Neu5Gc. We studied the presence of Neu5Gc on hADSC/MSCs cultured with FBS and human immune response mediated by Neu5Gc. Our data indicated that hADSC/MSCs cultured with FBS expressed Neu5Gc and human natural preformed antibodies could bind to hADSC/MSCs. However, hADSC/MSCs express complement regulatory proteins such as CD46, CD55, and CD59 and is largely resistant to complement-mediated cytotoxity (CMC). hADSC/MSCs cultured with FBS could be injured by antibody dependent cell-mediated cytotoxicity (ADCC) mechanism. Furthermore, human monocyte derived macrophages could phagocytose hADSC/MSCs cultured with FBS and this phagocytosis activity increased in the presence of human serum. Culturing the hADSC/MSCs with heat-inactivated human serum for a week could markedly reduce Neu5Gc on hADSC/MSCs and prevented immune responses mediated by Neu5Gc, such as human natural preformed antibodies binding, ADCC, and phagocytosis. Adipogenic and osteogenic differentiation potential of hADSC/MSCs cultured with heat-inactivated human serum was not less than those cultured with FBS. For stem cell therapies based on hADSC/MSCs to be realized, hADSC/MSCs that presented Neu5Gc on their cell surfaces after exposure to FBS should be clean up to be rescued from xenogenic rejection. PMID: 19863253 [PubMed - as supplied by publisher] |
| Lineage Enforcement by Inductive Mesenchyme on Adult Epithelial Stem Cells across Developmental Germ Layers.
October 30, 2009 at 5:07 am
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| | Lineage Enforcement by Inductive Mesenchyme on Adult Epithelial Stem Cells across Developmental Germ Layers. Stem Cells. 2009 Oct 27; Authors: Taylor RA, Wang H, Wilkinson SE, Richards MG, Britt K, Vaillant F, Lindeman GJ, Visvader JE, Cunha GR, St John J, Risbridger GP During development, cell differentiation is accompanied by the progressive loss of pluripotent gene expression and developmental potential, although de-differentiation in specialized cells can be induced by reprogramming strategies indicating that transdifferentiation potential is retained in adult cells. The stromal niche provides differentiating cues to epithelial stem cells (SCs), but current evidence is restricted to tissue types within the same developmental germ layer lineage. Anticipating the use of adult SCs for tissue regeneration, we examined if stroma can enforce lineage commitment across germ layer boundaries and promote transdifferentiation of adult epithelial SCs. Here, we report tissue-specific mesenchyme instructing epithelial cells from a different germ layer origin to express dual phenotypes. Prostatic stroma induced mammary epithelia (or enriched Lin(-)CD29(HI)CD24(+/MOD) mammary SCs) to generate glandular epithelia expressing both prostatic and mammary markers such as steroid hormone receptors and transcription factors including Foxa1, Nkx3.1 and GATA-3. Array data implicated Hh and Wnt pathways in mediating stromal-epithelial interactions (validated by increased Cyclin D1 expression). Other recombinants of prostatic mesenchyme and skin epithelia, or preputial gland mesenchyme and bladder or esophageal epithelia, showed foci expressing new markers adjacent to the original epithelial differentiation (e.g. sebaceous cells within bladder urothelium), confirming altered lineage specification induced by stroma and evidence of cross-germ layer transdifferentiation. Thus, stromal cell niche is critical in maintaining (or re-directing) differentiation in adult epithelia. In order to use adult epithelial SCs in regenerative medicine, we must additionally regulate their intrinsic properties to prevent (or enable) transdifferentiation in specified SC niches. PMID: 19862839 [PubMed - as supplied by publisher] |
| Down with the erythropoietin. Long live the erythropoietin!
October 30, 2009 at 5:07 am
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| | Down with the erythropoietin. Long live the erythropoietin! Curr Drug Targets. 2009 Oct;10(10):1028-32 Authors: Buemi M, Lacquaniti A, Bolignano D, Cernaro V, Campo S, Grasso G, Buemi A, Donato V, Sturiale A In recent years the use of erythropoietin has exploded, and the anaemia of patients with chronic renal failure has been practically resolved with the administration of rHuEpo (recombinant human, Erythropoietin). However, as a result of an intense commercial campaign, strong therapies with this growth hormone, prescribed to achieve surprising sporting performances, got athletes to run the risk of thrombosis and vascular accidents because of red blood cells increase. Erythropoietin represents a significant subject of research. In fact, besides the ability of stimulating erythrocyte production, it has many pleiotropic effects. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on central nervous system and cardiovascular system through various mechanisms, among which a key role seems to be held by the ability to stimulate angiogenesis. The consequent problem is that anaemia therapy with rHuEpo in patients with cancer may accelerate the progression of neoplastic disease by promoting tumour angiogenesis and, thus, metastasization. The study of angiogenic process in tumours led to the synthesis of drugs that, blocking VEGF, exert an anti-angiogenic action, contrasting cancer spread. However, benefits are relatively modest. Is erythropoietin perhaps the further angiogenic hormone to block in tumour pathology? Therefore, Epo plays a role in Regenerative Medicine since it intervenes in a persistent natural regenerative activity of humans: angiogenesis. The understanding of the regeneration mechanisms of complex structures in the adult salamander has opened original lines of research. Regenerative Medicine tries to develop therapeutic pathways through the stimulation of natural regenerative processes in humans. PMID: 19860645 [PubMed - in process] |
| Periodontal Tissue Engineering and Regeneration: Current Approaches and Expanding Opportunities.
October 30, 2009 at 5:07 am
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| | Periodontal Tissue Engineering and Regeneration: Current Approaches and Expanding Opportunities. Tissue Eng Part B Rev. 2009 Oct 27; Authors: Chen FM, Jin Y The management of periodontal tissue defects that result from periodontitis represents a medical and socioeconomic challenge. Concerted efforts have been and still are being made to accelerate and augment periodontal tissue and bone regeneration, including a range of regenerative surgical procedures, the development of a variety of grafting materials and the use of recombinant growth factors. More recently, tissue-engineering strategies including new cell- and/or matrix-based dimensions are also being developed, analysed and employed for periodontal regenerative therapies. Tissue engineering in periodontology applies the principles of engineering and life sciences toward the development of biological techniques that can restore lost alveolar bone, periodontal ligament and root cementum. It is based on an understanding of the role of periodontal formation and aims to grow new functional tissues rather than to build new replacements of periodontium. Whilst tissue engineering has merged to create more opportunities for predictable and optimal periodontal tissue regeneration, the technique and design for pre-clinical and clinical studies remain in their early stages. To date, the reconstruction of small- to moderate-sized periodontal bone defects using engineered cell-scaffold constructs is technically feasible, and some of the currently developed concepts may represent alternatives for certain ideal clinical scenarios. However, the predictable reconstruction of the normal structure and functionality of a tooth-supporting apparatus remains challenging. This review summarises current regenerative procedures for periodontal healing and regeneration and explores their progress and difficulties in clinical practice, with particular emphasis placed upon current challenges and future possibilities associated with tissue engineering strategies in periodontal regenerative medicine. PMID: 19860551 [PubMed - as supplied by publisher] |
| Generation of functional eyes from pluripotent cells.
October 30, 2009 at 5:07 am
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| | Generation of functional eyes from pluripotent cells. PLoS Biol. 2009 Aug;7(8):e1000174 Authors: Viczian AS, Solessio EC, Lyou Y, Zuber ME Pluripotent cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision. PMID: 19688031 [PubMed - indexed for MEDLINE] | | | 
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