|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Strategies for regeneration of the bone using porcine adult adipose-derived mesenchymal stem cells. Theriogenology. 2011 Feb 25; Authors: Monaco E, Bionaz M, Hollister SJ, Wheeler MB Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice, thus far, for stem cell therapy for bone regeneration. However, it has been shown that adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC. Moreover, ASC are much more abundant, more accessible and have lower donor morbidity, which combined may make ASC a better alternative to BMSC. ASC are also able to migrate to the site of injury and have immunosuppressive abilities similar to BMSC. Further, ASC have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species, greatly enhancing the healing of critical size defects. The use of scaffolds in combination with ASC and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Some critical elements include ASC-scaffold interactions and appropriate three-dimensional design of the porous osteoinductive structures. This review examines data that provides strong support for the clinical translation of ASC for bone regeneration. PMID: 21354606 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | REGENERATION OF INFARCTED MYOCARDIUM WITH RESVERATROL-MODIFIED CARDIAC STEM CELLS. J Cell Mol Med. 2011 Feb 25; Authors: Gorbunov N, Petrovski G, Gurusamy N, Ray D, Kim DH, Das DK The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells after transplantation. Indeed, the vast majority of host-transfused cells do not survive beyond 24 to 72 hours. In order to increase the survival and engraftment of implanted cardiac stem cells in the host, we developed a technique of treating these cells with resveratrol, and tested it in a rat model of LAD (left anterior descending) occlusion. Multipotent clonogenic cardiac stem cells isolated from rat heart and stably transfected with EGFP were pre-treated with 2.5 μM resveratrol for 60 minutes. Rats were anesthetized, hearts opened and the LAD occluded to induce heart attack. One week later, the cardiac reduced environment was confirmed in resveratrol treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). M-mode echocardiography after stem cell therapy, showed improvement in cardiac function (left ventricular ejection fraction, fractional shortening and cardiac output) in both, the treated and control group after 7 days, but only resveratrol-modified stem cell group revealed improvement in cardiac function at the end of one, two and four months time. The improvement of cardiac function was accompanied by enhanced stem cell survival and engrafment as evidenced by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as evidenced by the expression of EGFP up to four months after LAD occlusion in the resveratrol treated stem cell group. Expression of stromal cell-derived factor (SDF-1) and myosin conclusively demonstrated homing of stem cells in the infarcted myocardium, its regeneration leading to improvement of cardiac function. PMID: 21352470 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Strategies for regeneration of the bone using porcine adult adipose-derived mesenchymal stem cells. Theriogenology. 2011 Feb 25; Authors: Monaco E, Bionaz M, Hollister SJ, Wheeler MB Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice, thus far, for stem cell therapy for bone regeneration. However, it has been shown that adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC. Moreover, ASC are much more abundant, more accessible and have lower donor morbidity, which combined may make ASC a better alternative to BMSC. ASC are also able to migrate to the site of injury and have immunosuppressive abilities similar to BMSC. Further, ASC have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species, greatly enhancing the healing of critical size defects. The use of scaffolds in combination with ASC and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Some critical elements include ASC-scaffold interactions and appropriate three-dimensional design of the porous osteoinductive structures. This review examines data that provides strong support for the clinical translation of ASC for bone regeneration. PMID: 21354606 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | AMPK Mediates Adipose Stem Cell-Stimulated Neuritogenesis of PC12 Cells. Neuroscience. 2011 Feb 22; Authors: Tan B, Luan Z, Wei X, He Y, Wei G, Johnstone BH, Farlow M, Du Y Adipose tissue stroma contains a population of mesenchymal stem cells, which support repair of damaged tissues through the protective effects of secreted trophic factors. Neurotrophic factors, including nerve growth factor (NGF) have been identified in media collected from cultured adipose-derived stem cells (ASC). We previously demonstrated that administration of cell-free ASC conditioned medium (ASC-CM) at 24 hours after injury reduced lesion volume and promoted functional recovery in a rat model of neonatal brain hypoxic-ischemic (HI) injury. The timing of administration well after the peak in neural cell apoptosis in the affected region suggests that regeneration of lost neurons is promoted by factors in ASC-CM. In this study, we determined which of the factors in ASC-CM could induce neurogenesis by testing the ability of the mixture, either whole or after inactivating specific components, to stimulate neurite outgrowth in vitro using the neurogenic cell line PC12. Neuritogenesis in PC12 cells treated with ASC-CM was observed at a level comparable to that observed with purified recombinant NGF. It was observed that NGF in ASC-CM was mainly responsible for inducing PC12 cell neuritogenesis. Interestingly, both ASC-CM and NGF induced PC12 cell neuritogenesis through activation of the AMP-activated kinase (AMPK) pathway which is the central protein involved in controlling many critical functions in response to changes in the cellular energy status. Pharmacological and genetic inhibition of AMPK activity greatly reduced neuritogenesis in PC12 cells. These results suggest that, in addition to possessing neuroprotective properties, ASC-CM mediates repair of damaged tissues through inducing neuronal differentiation via NGF-induced AMPK activation. PMID: 21352901 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Improved cellular response on multiwalled carbon nanotube-incorporated electrospun polyvinyl alcohol/chitosan nanofibrous scaffolds. Colloids Surf B Biointerfaces. 2011 Feb 24; Authors: Liao H, Qi R, Shen M, Cao X, Guo R, Zhang Y, Shi X We report the fabrication of multiwalled carbon nanotube (MWCNT)-incorporated electrospun polyvinyl alcohol (PVA)/chitosan (CS) nanofibers with improved cellular response for potential tissue engineering applications. In this study, smooth and uniform PVA/CS and PVA/CS/MWCNTs nanofibers with water stability were formed by electrospinning, followed by crosslinking with glutaraldehyde vapor. The morphology, structure, and mechanical properties of the formed electrospun fibrous mats were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing, respectively. We showed that the incorporation of MWCNTs did not appreciably affect the morphology of the PVA/CS nanofibers; importantly the protein adsorption ability of the nanofibers was significantly improved. In vitro cell culture of mouse fibroblasts (L929) seeded onto the electrospun scaffolds showed that the incorporation of MWCNTs into the PVA/CS nanofibers significantly promoted cell proliferation. Results from this study hence suggest that MWCNT-incorporated PVA/CS nanofibrous scaffolds with small diameters (around 160nm) and high porosity can mimic the natural extracellular matrix well, and potentially provide many possibilities for applications in the fields of tissue engineering and regenerative medicine. PMID: 21353768 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cartilage regeneration by bone marrow cells-seeded scaffolds. J Biomed Mater Res A. 2010 Dec 1;95(3):735-40 Authors: Wegener B, Schrimpf FM, Bergschmidt P, Pietschmann MF, Utzschneider S, Milz S, Jansson V, Müller PE Different approaches exist for the treatment of small articular cartilage defects. Several studies show comparable results for autologous chondrocyte implantation (ACI) and microfracture. Unfortunately, the fibrocartilage resulting from microfracture has neither the structure nor the mechanical properties of hyaline cartilage, even though the adult mesenchymal stem cells, which immigrate into the defect, are supposed to differentiate into chondrocytes. This study was performed to examine the capacity of a resorbable implant made from polylactide-co-glycolide acid (PGLA)-fleece combined with autologous bone marrow cells fixed with a fibrin/thrombin-clot in the weight-bearing area of the femoral condyle of mature sheep. For this study, six defects were treated with either the PGLA-implant alone or with a combination of the implant with added fibrin glue or were left untreated to serve as controls. The animals were sacrificed after 12 weeks; the operated knees were removed and examined by measuring the covering of the defect with cartilaginous tissue and according to the score of O'Driscoll. Additional criteria such as immunolabeling for collagen II and aggrecan were included. Results showed that no improvement of the tissue quantity or quality could be achieved by increasing the cell load of the implant with cells fixed by fibrin glue. PMID: 20725984 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Embryonic body formation using the tapered soft stencil for cluster culture device. Biomaterials. 2011 Feb 25; Authors: Yukawa H, Noguchi H, Hayashi S Induced pluripotent stem (iPS) cells are expected to provide a source of tissue, a renewable cell source for tissue engineering, and a method for in vitro drug screening for patient-specific or disease-specific treatment. A simple technology by which iPS cells can be differentiated effectively and in large quantities is strongly desired. In this paper, a new device (Tapered Soft Stencil for Cluster Culture: TASCL) is proposed for the easy and efficient formation of EBs which can be used in regenerative medicine. This device was compared with the two major methods currently being evaluated, namely the HD method and the Terasaki(®) plate (MWC substitution), in terms of the efficiency, morphology and acquired number of EB formation. Using the TASCL device, the shape of the EBs formed was almost a perfect sphere, and the formation was also faster than for the two other methods. There was little variability in the number of cells. Moreover, EBs formed using the TASCL device had the ability to differentiate into all three germ layers, and differentiation of EBs from the TASCL culture into hepatic cells was confirmed. In conclusion, it appears that the TASCL device can be utilized for EB formation to generate cells for regenerative medicine applications. PMID: 21354615 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell attachment and response to photo - cured, degradable bone adhesives containing tricalcium phosphate and purmorphamine. Acta Biomater. 2011 Feb 24; Authors: Gellynck K, Neel EA, Li H, Mardas N, Donos N, Buxton P, Young AM The study aim was to quantify and provide evidence as to how addition of β-TCP and the hedgehog agonist purmorphamine to a degradable bone adhesive affects cell attachment / proliferation and hedgehog pathway activation. FTIR demonstrated high levels (75 wt%) of tricalcium phosphate (β-TCP) addition reduced photo-cure rate of the chosen poly(propylene glycol-co-lactide) dimethacrylate bone adhesive (PPLM) but this problem was overcome through increased light exposure. In PBS, total surface mass loss of set, 15 mm diameter PPLM films, was ∼3.2 mg in12 weeks irrespective of thickness (200 or 400 μm) or β-TCP level (50 or 75 wt %). With 400 μm samples there was additional bulk material loss. Proliferation of pre-osteoblast cells (MC3T3-E1) on the set adhesive surfaces was enhanced by sample thickness decline or filler content increase. Degradation evidence suggested effects of both variables were due to reduced acidic polymeric degradation products. Activation of the hedgehog pathway was quantified by measuring Gli expression of Light II reporter cells. 0.01 and 0.1 wt% purmorphamine in composite discs (400 μm, 75 wt% β-TCP) enhanced Gli expression of attached cells 2 and 5 fold respectively without influencing their number. Pre - storage of the composite samples in culture medium had no detrimental effect on this response. Furthermore, sample storage mediums gave no enhanced Gli expression of cells on tissue culture plastic. This suggests drug release levels were very low. Purmorphamine and β-TCP incorporation in PPLM adhesives might therefore provide prolonged enhancement of in vivo bone repair without drug systemic side effects. PMID: 21354477 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of VEGF loading on scaffold-confined vascularization. J Biomed Mater Res A. 2010 Dec 1;95(3):783-92 Authors: Lindhorst D, Tavassol F, von See C, Schumann P, Laschke MW, Harder Y, Bormann KH, Essig H, Kokemüller H, Kampmann A, Voss A, Mülhaupt R, Menger MD, Gellrich NC, Rücker M Adequate vascularization of tissue-engineered constructs remains a major challenge in bone grafting. In view of this, we loaded ß-tricalcium-phosphate (ß-TCP) and porous poly(L-lactide-co-glycolide) (PLGA) scaffolds via collagen coating with vascular endothelial growth factor (VEGF) and studied whether the VEGF loading improves scaffold angiogenesis and vascularization. Dorsal skinfold chambers were implanted into 48 balb/c mice, which were assigned to 6 groups (n = 8 each). Uncoated (controls), collagen-coated, and additionally VEGF-loaded PLGA and ß-TCP scaffolds were inserted into the chambers. Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed repeatedly during a 14-day observation period using intravital fluorescence microscopy. Furthermore, VEGF release from PLGA und ß-TCP scaffolds was studied by ELISA. Micromorphology was studied from histological specimens. Unloaded ß-TCP scaffolds showed an accelerated and increased angiogenic response when compared with unloaded PLGA scaffolds. In vitro, PLGA released significantly higher amounts of VEGF compared with ß-TCP at the first two days resulting in a rapid drop of the released amount at the following days up to day 7 where the VEGF release was negligible. Nonetheless, in vivo VEGF loading increased neovascularization, especially in ß-TCP scaffolds. This increased vascularization was associated with a temporary leukocytic response with pronounced leukocyte-endothelial cell interaction at days 3 and 6. Histology revealed adequate host tissue response and engraftment of both ß-TCP and PLGA scaffolds. Our study demonstrates that ß-TCP scaffolds offer more suitable conditions for vascularization than PLGA scaffolds, in particular if they are loaded with VEGF. PMID: 20725981 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Vascular prostheses: 50 years of advancement from synthetic towards tissue engineering and cell therapy]. Rozhl Chir. 2010 Jan;89(1):85-94 Authors: Chlupác J, Filová E, Bacáková L Since more than 50 years, the gold standard in synthetic vascular prostheses has been represented by polyethylene terephtalate (PET, Dacron) and expanded polytetrafluoroethylene (ePTFE). These polymers perform well as sustitutes of large-caliber vessels, however, their long-term patencies are disappointing in small-caliber applications (< 6 mm). Thus, patient's own artery or vein remains the material of choice in coronary, crural or microvessel bypass surgery. Synthetic materials fail due to thrombosis and insufficient healing process that consists in highly incomplete endothelial cells coverage and intimal hyperplasia caused by compliance mismatch and hemodynamic imbalance. To find better small-caliber vascular graft, surgical techniques have been modified, novel biomaterials have been investigated and cell and tissue culture technologies have been adopted. Partly or fully tissue-engineered vascular grafts have been produced and experimentally and clinically evaluated with some promising result. The aim of this review is to briefly list currently used and examined vascular graft materials with special attention to cell/biomaterial ineractions, tissue engineering and authors' own experience. PMID: 21351411 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Treatment and research progress of massive rotator cuff tears]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Jan;25(1):61-5 Authors: Liu G, Huang F, Qin T To review the progress in the treatment and research of massive rotator cuff tears. PMID: 21351612 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A novel tissue-engineered approach to problems of the postpneumonectomy space. Ann Thorac Surg. 2011 Mar;91(3):880-6 Authors: Tsunooka N, Hirayama S, Medin JA, Liles WC, Keshavjee S, Waddell TK Transfer of viable tissue flaps and thoracoplasty are effective against pleural space complications after pneumonectomy but highly disfiguring. The aim of this study was to explore the possibility of engineered tissue to treat space complications after pneumonectomy. PMID: 21353020 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Different effects of implanting vascular bundles and sensory nerve tracts on the expression of neuropeptide receptors in tissue-engineered bone in vivo. Biomed Mater. 2010 Oct;5(5):055002 Authors: Chen SY, Qin JJ, Wang L, Mu TW, Jin D, Jiang S, Zhao PR, Pei GX We investigated whether implantation of vascular bundles or sensory nerves affected the expression of calcitonin gene-related peptide type I receptor (CGRP1R) and neuropeptide Y1 receptor (NPY1R) in tissue-engineered bone. We implanted osteogenically induced bone marrow mesenchymal stem cells (BMSCs) with β-tricalcium phosphate (β-TCP) as the scaffold material either with sensory nerve tracts (group I, n = 18), vascular bundles (group II, n = 18) or alone (group III, n = 18) to repair a 1.2 cm femur defect in the rabbit. Better osteogenesis was observed by x-ray and histology in groups I and II than in group III at 4, 8 and 12 weeks. Within the new bone, the mRNA levels of the two neuropeptide receptors determined by real-time PCR increased through week 8, and then gradually decreased (P < 0.05). Expression of the neuropeptide receptors determined by immunohistochemistry was lowest at 4 weeks (P < 0.05) and was higher in group II than in group I (P < 0.05). Expression was significantly higher in groups I and II than in group III at all time points. We conclude that implanting vascular bundles into tissue-engineered bone can significantly improve the early expression of CGRP1R and NPY1R. In contrast, implantation of sensory nerves did not show the same dramatic effect as implantation of vascular bundles. PMID: 20826910 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis of Bio-functionalized Three-dimensional Titania Nanofibrous Structures Using Femtosecond Laser Ablation. Acta Biomater. 2011 Feb 24; Authors: Tavangar A, Tan B, Venkatakrishnan K The primary objective of current tissue regeneration research is to synthesize nano-based platforms that can induce guided, controlled, and rapid healing. Titanium nanotubes have been extensively considered as a new biomaterial for biosensors, implants, cell growth, tissue engineering, and drug delivery systems. However, cell adhesion to nanotube is poor due to their chemical inertness as well as one-dimensional structure and surface modification is required to enhance nanotube-cell interaction. While there are considerable studies on growing titanium nanotubes, synthesizing a threedimensional (3-D) nano-architecture which can act as a growth support platform for bone and stem cells has not been reported so far. Therefore, we present a novel technique to synthesize and grow 3-D titania interwoven nanofibrous structures on titanium substrate using femtosecond laser in ambient conditions. This surface architecture incorporate the functions of 3D nano-scaled topography and modified chemical properties to improve osseointegration while at the same time leaving space for delivering other functional agents. The results indicate that laser pulse repetition can control the density and pore size of engineered nanofibrous structure. In vitro experiments reveal that the titania nanofibrous architecture possesses an excellent bioactivity and can induce rapid, uniform, and controllable bone-like apatite precipitation once immersed in simulated body fluids (SBF). This approach for synthesizing 3-D titania nanofibrous structures suggest considerable outlook for promoting Ti interfacial properties to develop new functional biomaterials for various biomedical applications. PMID: 21354476 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Strategies for regeneration of the bone using porcine adult adipose-derived mesenchymal stem cells. Theriogenology. 2011 Feb 25; Authors: Monaco E, Bionaz M, Hollister SJ, Wheeler MB Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice, thus far, for stem cell therapy for bone regeneration. However, it has been shown that adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC. Moreover, ASC are much more abundant, more accessible and have lower donor morbidity, which combined may make ASC a better alternative to BMSC. ASC are also able to migrate to the site of injury and have immunosuppressive abilities similar to BMSC. Further, ASC have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species, greatly enhancing the healing of critical size defects. The use of scaffolds in combination with ASC and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Some critical elements include ASC-scaffold interactions and appropriate three-dimensional design of the porous osteoinductive structures. This review examines data that provides strong support for the clinical translation of ASC for bone regeneration. PMID: 21354606 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Infection and tissue engineering in segmental bone defects-a mini review. Curr Opin Biotechnol. 2011 Feb 25; Authors: Nair MB, Kretlow JD, Mikos AG, Kasper FK As tissue engineering becomes more of a clinical reality through the ongoing bench to bedside transition, research in this field must focus on addressing relevant clinical situations. Although most in vivo work in the area of bone tissue engineering focuses on bone regeneration within sterile, surgically created defects, there is a growing need for the investigation of bone tissue engineering approaches within contaminated or scarred wound beds, such as those that may be encountered following traumatic injury or during delayed reconstruction/regeneration. Significant work has been performed in the area of local drug delivery via biomaterial carriers, but there is little intersection in the available literature between antibiotic delivery and tissue regeneration. In this review, we examine recent advances in segmental bone defect animal models, bone tissue engineering, and drug delivery with the goal of identifying promising approaches and areas needing further investigation towards developing both a better understanding of and new tissue engineering approaches for addressing infection control while simultaneously initiating bone regeneration. PMID: 21354782 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioorthogonal dual functionalization of self-assembling peptide fibers. Biomaterials. 2011 Feb 23; Authors: Mahmoud ZN, Gunnoo SB, Thomson AR, Fletcher JM, Woolfson DN The ability to modify peptide- and protein-based biomaterials selectively under mild conditions and in aqueous buffers is essential to the development of certain areas of bionanotechnology, tissue engineering and synthetic biology. Here we show that Self-Assembling peptide Fibers (SAFs) can incorporate multiple modified peptides non-covalently, stoichiometrically and without disrupting their structure or stability. The modified peptides contain groups suitable for post-assembly click reactions in water, namely azides and alkenes. Labeling of these groups is achieved using the orthogonal Cu(I)-catalyzed azide-alkyne and photoinitiated thiol-ene reactions, respectively. Functionalization is demonstrated through the conjugation of biotin followed by streptavidin-nanogold particles, or rhodamine, and visualized by electron and light microscopy, respectively. This has been shown for fibers harboring either or both of the modified peptides. Furthermore, the amounts of each modified peptide in the fibers can be varied with concomitant changes in decoration. This approach allows the design and assembly of fibers with multiple functional components, paving the way for the development of multi-component functionalized systems. PMID: 21353303 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Activin/Nodal signaling and pluripotency. Vitam Horm. 2011;85:39-58 Authors: Chng Z, Vallier L, Pedersen R Maintenance of a pluripotent cell population during mammalian embryogenesis is crucial for the proper generation of extraembryonic and embryonic tissues to ensure intrauterine survival and fetal development. Pluripotent stem cells derived from early stage mammalian embryos are known as "embryonic stem cells." Such embryo-derived stem cells can proliferate indefinitely in vitro and give rise to derivatives of all three primary germ layers. Their potential for clinical and commercial applications has sparked great excitement within scientific and lay communities. Identification of the signaling pathways controlling stem cell pluripotency and differentiation provides knowledge-based approaches to manipulate stem cells for regenerative medicine. One of the signaling cascades that has been identified in the control of stem cell pluripotency and differentiation is the Activin/Nodal pathway. Here, we describe the differences among pluripotent cell types and discuss the latest findings on the molecular mechanisms involving Activin/Nodal signaling in controlling their pluripotency and differentiation. PMID: 21353875 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The role of activin/nodal and wnt signaling in endoderm formation. Vitam Horm. 2011;85:207-16 Authors: Payne C, King J, Hay D Human embryonic stem cells (hESCs) are located within the inner cell mass of the preimplantation blastocysts. hESCs exhibit two important properties, the ability to generate exact copies of themselves, termed self-renewal, and pluripotency, the ability of stem cells to differentiate into every cell type of the embryo. This means that in theory it may be possible to generate an inexhaustible supply of primary human somatic cells in vitro which are suitable for application in regenerative medicine. Maintaining stem cell self-renewal and eliciting differentiation are dependent on the coordination of a number of signaling pathways which include members of the transforming growth factor beta (TGFβ) and Wnt families. The work in our laboratory has focused on the efficient generation of hepatocyte-like cells (HLCs) from hESCs and induced pluripotent stem cells (iPSCs). In order to mimic signaling during primitive streak and endoderm development, we have utilized TGFβ and Wnt signaling pathways in vitro. This has resulted in the generation of homogeneous populations of HLCs exhibiting liver specific function. This chapter will focus on TGFβ and Wnt signaling pathways and their role in primitive streak, endoderm, and HLC development. PMID: 21353882 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Removal of lactate dehydrogenase-elevating virus from human-in-mouse breast tumor xenografts by cell-sorting. J Virol Methods. 2011 Feb 24; Authors: Liu H, Bockhorn J, Dalton R, Chang YF, Qian D, Zitzow LA, Clarke MF, Greene GL Lactate dehydrogenase-elevating virus (LDV) can infect transplantable mouse tumors or xenograft tumors in mice through LDV-contaminated mouse biological materials, such as Matrigel, or through mice infected with LDV. LDV specifically infects mouse macrophages and alters immune system and tumor phenotype. The traditional approaches to remove LDV from tumor cells, by transplanting tumors into rats or culturing tumor cells in vitro, are inefficient, labor-intensive and time-consuming. Furthermore, these approaches are not feasible for primary tumor cells that cannot survive tissue culture conditions or that may change phenotype in rats. This study reports that fluorescence-activated cell sorting (FACS) is a simple and efficient approach for purifying living primary human breast tumor cells from LDV(+) mouse stromal cells, which can be completed in a few hours. When purified from Matrigel contaminated LDV(+) tumors, sorted human breast tumor cells, as well as tumors grown from sorted cells, were shown to be LDV-free, as tested by PCR. Our data demonstrate that cell sorting is effective, much faster and less likely to alter tumor cell phenotype than traditional methods for removing LDV from xenograft models. This approach may also be used to remove other rodent-specific viruses from models derived from distinct tissues or species with sortable markers, where virus does not replicate in the cells to be purified. PMID: 21354210 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Canonical WNT Signaling Enhances Stem Cell Expression in the Developing Heart without a Corresponding Inhibition of Cardiogenic Differentiation. Stem Cells Dev. 2011 Feb 25; Authors: Martin LK, Mezentseva NV, Bratoeva M, Ramsdell AF, Eisenberg CA, Eisenberg LM WNT signaling has been shown to influence the development of the heart. Although recent data suggested canonical WNTs promote the emergence and expansion of cardiac progenitors in the pregastrula embryo, it has long been accepted that once gastrulation begins, canonical WNT signaling needs to be suppressed for cardiac development to proceed. Yet, this latter supposition appears to be odds with the expression of multiple canonical WNTs in the developing heart. The present study examining the effect of ectopic canonical WNT signaling on cardiogenesis in the developing frog was designed to test the hypothesis that heart formation is dependent on the inhibition of canonical WNT activity at the onset of gastrulation. Here we report that cardiac differentiation of explanted precardiac tissue from the dorsal marginal zone was not suppressed by exposure to WNT1 protein, although expression of Tbx5, Tbx20, and Nkx2.5 was selectively reduced. Pharmacological activation of WNT signaling in intact embryos using the GSK3 inhibitor SB415286 did not prevent the formation of an anatomically normal and functionally sound heart, with the only defect observed being lower levels of the cardiac transcription factor Nkx2.5. In both the explant and whole embryo studies, expression of muscle genes and proteins were unaffected by ectopic canonical WNT signaling. In contrast, canonical Wnt signaling upregulated expression of the cardiac stem cell marker c-kit and pluripotency genes Oct25 and Oct60. However, this regulatory stimulation of stem cells did not come at the expense of blocking cardiac progenitors from differentiating. PMID: 21351874 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Normal human epidermal keratinocytes react differently than HaCaT keratinocyte cell line on exposure to Propionibacterium acnes. J Dermatol. 2010 Sep 20; Authors: Akaza N, Akamatsu H, Kishi M, Mizutani H, Nakata S, Matsunaga K PMID: 21352277 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [First applications of matrix therapy in plastic and aesthetic surgery]. Ann Chir Plast Esthet. 2010 Oct;55(5):421-8 Authors: Zakine G, Le Louarn C A new medical device based on a concept of the reconstruction of the extracellular matrix by a molecule belonging to the family of the ReGeneraTing Agents (RGTA(®)) has just been available to treat skin lesions. RGTA(®) are biodegradable polymers engineered to mimic heparan-sulfate in the extracellular matrix of damaged tissue. RGTA(®) improves tissue healing in several animal models, by stabilizing and protecting heparin-binding growth factors (HBGFs) and matrix proteins. We have evaluated the effects of this device containing RGTA(®) on cutaneous cicatrisation in a group of patients treated by reduction mammoplasty and in a group operated by a centrofacial lifting. PMID: 20869155 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Altered distribution of M2 and M4 muscarinic receptor expression in vitiligo. J Dermatol. 2010 Sep 28; Authors: Chaichalotornkul S, Udompataikul M, Showpittapornchai U, Palungwachira P, Pradidarcheep W PMID: 21352345 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Embryonic body formation using the tapered soft stencil for cluster culture device. Biomaterials. 2011 Feb 25; Authors: Yukawa H, Noguchi H, Hayashi S Induced pluripotent stem (iPS) cells are expected to provide a source of tissue, a renewable cell source for tissue engineering, and a method for in vitro drug screening for patient-specific or disease-specific treatment. A simple technology by which iPS cells can be differentiated effectively and in large quantities is strongly desired. In this paper, a new device (Tapered Soft Stencil for Cluster Culture: TASCL) is proposed for the easy and efficient formation of EBs which can be used in regenerative medicine. This device was compared with the two major methods currently being evaluated, namely the HD method and the Terasaki(®) plate (MWC substitution), in terms of the efficiency, morphology and acquired number of EB formation. Using the TASCL device, the shape of the EBs formed was almost a perfect sphere, and the formation was also faster than for the two other methods. There was little variability in the number of cells. Moreover, EBs formed using the TASCL device had the ability to differentiate into all three germ layers, and differentiation of EBs from the TASCL culture into hepatic cells was confirmed. In conclusion, it appears that the TASCL device can be utilized for EB formation to generate cells for regenerative medicine applications. PMID: 21354615 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A novel tissue-engineered approach to problems of the postpneumonectomy space. Ann Thorac Surg. 2011 Mar;91(3):880-6 Authors: Tsunooka N, Hirayama S, Medin JA, Liles WC, Keshavjee S, Waddell TK Transfer of viable tissue flaps and thoracoplasty are effective against pleural space complications after pneumonectomy but highly disfiguring. The aim of this study was to explore the possibility of engineered tissue to treat space complications after pneumonectomy. PMID: 21353020 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Improved cellular response on multiwalled carbon nanotube-incorporated electrospun polyvinyl alcohol/chitosan nanofibrous scaffolds. Colloids Surf B Biointerfaces. 2011 Feb 24; Authors: Liao H, Qi R, Shen M, Cao X, Guo R, Zhang Y, Shi X We report the fabrication of multiwalled carbon nanotube (MWCNT)-incorporated electrospun polyvinyl alcohol (PVA)/chitosan (CS) nanofibers with improved cellular response for potential tissue engineering applications. In this study, smooth and uniform PVA/CS and PVA/CS/MWCNTs nanofibers with water stability were formed by electrospinning, followed by crosslinking with glutaraldehyde vapor. The morphology, structure, and mechanical properties of the formed electrospun fibrous mats were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing, respectively. We showed that the incorporation of MWCNTs did not appreciably affect the morphology of the PVA/CS nanofibers; importantly the protein adsorption ability of the nanofibers was significantly improved. In vitro cell culture of mouse fibroblasts (L929) seeded onto the electrospun scaffolds showed that the incorporation of MWCNTs into the PVA/CS nanofibers significantly promoted cell proliferation. Results from this study hence suggest that MWCNT-incorporated PVA/CS nanofibrous scaffolds with small diameters (around 160nm) and high porosity can mimic the natural extracellular matrix well, and potentially provide many possibilities for applications in the fields of tissue engineering and regenerative medicine. PMID: 21353768 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Treatment of recalcitrant ulcers with allogeneic platelet gel from pooled platelets in aged hypomobile patients. Biologicals. 2011 Feb 23; Authors: Greppi N, Mazzucco L, Galetti G, Bona F, Petrillo E, Smacchia C, Raspollini E, Cossovich P, Caprioli R, Borzini P, Rebulla P, Marconi M We evaluated growth factor contents and clinical efficacy of allogeneic platelet gel (PG) prepared with standard blood banking procedures from routine platelet concentrates (PCs) obtained from buffy coats. The PGs were used to treat 11 hypomobile very elderly patients unable to undergo autologous blood processing and previously ineffectively treated with expensive advanced medications for 8-275 weeks. PGs were prepared by platelet activation with human thrombin or commercial batroxobin. Median and range growth factor contents (ng/mL) were: platelet derived growth factor (PDGF-AB/-BB) 112 (31-157) and 20 (3.8-34); transforming growth factor (TGF-β1/-β2) 214 (48-289) and 0.087 (0.03-0.28); basic-fibroblast growth factor (b-FGF) 0.03 (0.006-0.214); vascular endothelial growth factor (VEGF) 1.15 (0.18-2.46); epidermal growth factor (EGF) 4.50 (0.87-6.64); insulin-like growth factor (IGF-l) 116 (72-156). In the clinical study, 222 PGs were used within 2 h of activation to treat 14 chronic skin ulcers in the 11 patients. No improvement was seen in 3 patients with 24, 27 and 30 cm(3) ulcers who could be treated for no more than 4, 7 and 8 weeks due to progressively worsening clinical conditions, while 11 ulcers with 3.2 cm(3) median size (range 0.2-3.6) in the remaining 8 patients showed 91 ± 14 % reduction after a median of 12 weeks (range 1-20). Cost of PG treatment (19,976 euro) amounted to about 10% of the ineffective advanced medication hospital reimbursement fees (191,236 euro). This study supports efficacy and feasibility of allogeneic PG to treat recalcitrant ulcers in very elderly hypomobile patients for whom autologous blood processing may be difficult. PMID: 21353597 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Calcium-mediated stress kinase activation by DMP1 promotes osteoblast differentiation. J Biol Chem. 2010 Nov 19;285(47):36339-51 Authors: Eapen A, Sundivakkam P, Song Y, Ravindran S, Ramachandran A, Tiruppathi C, George A Calcium signaling and calcium transport play a key role during osteoblast differentiation and bone formation. Here, we demonstrate that DMP1 mediated calcium signaling, and its downstream effectors play an essential role in the differentiation of preosteoblasts to fully functional osteoblasts. DMP1, a key regulatory bone matrix protein, can be endocytosed by preosteoblasts, triggering a rise in cytosolic levels of calcium that initiates a series of downstream events leading to cellular stress. These events include release of store-operated calcium that facilitates the activation of stress-induced p38 MAPK leading to osteoblast differentiation. However, chelation of intracellular calcium and inhibition of the p38 signaling pathway by specific pharmacological inhibitors and dominant negative plasmid suppressed this activation. Interestingly, activated p38 MAPK can translocate to the nucleus to phosphorylate transcription factors that coordinate the expression of downstream target genes such as Runx 2, a key modulator of osteoblast differentiation. These studies suggest a novel paradigm by which DMP1-mediated release of intracellular calcium activates p38 MAPK signaling cascade to regulate gene expression and osteoblast differentiation. PMID: 20841352 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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