|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Turning everything into brain? Neurosurgery. 2010 Aug;67(2):N16-7 Authors: Kundu B, Kuo JS, Dempsey RJ PMID: 20644402 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A case of local advanced penile cancer treated with multimodality therapy. Int J Clin Oncol. 2010 Oct;15(5):523-7 Authors: Kato M, Soga N, Arima K, Sugimura Y A 61-year-old man presented to our institution complaining of a putrescent left inguinal ulcerated tumor. Our diagnosis was penile cancer with bilateral inguinal lymph node metastasis and clinical staging T4N3M0. Here we report a case of local advanced penile cancer experimentally treated with a multimodal approach. PMID: 20396925 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Biomaterials for craniofacial reconstruction]. Laryngorhinootologie. 2009 May;88 Suppl 1:S48-63 Authors: Neumann A Biomaterials for reconstruction of bony defects of the skull comprise of osteosynthetic materials applied after osteotomies or traumatic fractures and materials to fill bony defects which result from malformations, traumata or tumor resections. Other applications concern functional augmentations for dental implants or asthetic augmentations in the region of the face. For ostheosynthesis, mini- and microplates from titanium alloys provide major advantages concerning biocompatibility, stability and individual fitting to the implant bed. The necessity of removal of asymptomatic plates and screws after fracture healing is still a controversial issue. Risks and costs of secondary surgery for removal face a low rate of complications (due to corrosion products) when the materials remains in situ. Resorbable osteosynthesis systems have similar mechanical stability and are especially useful in the growing skull. The huge variety of biomaterials for reconstruction of bony defects makes it difficult to decide which material is adequate for which indication and for which site. The optimal biomaterial that meets every requirement (e. g. biocompatibility, stability, intraoperative fitting, product safety, low costs etc.) does not exist. The different material types are (autogenous) bone and many alloplastics such as metals (mainly titanium), ceramics, plastics and composites. Future developments aim to improve physical and biological properties, especially concerning surface interactions. To date, tissue engineered bone is far from routine clinical application. PMID: 19353458 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The administration of BDNF and GDNF to the brain via PLGA microparticles patterned within a degradable PEG-based hydrogel: Protein distribution and the glial response. J Biomed Mater Res A. 2011 Mar;96(3):595-607 Authors: Lampe KJ, Kern DS, Mahoney MJ, Bjugstad KB Tailored delivery of neurotrophic factors (NFs) is a critical challenge that continues to inhibit strategies for guidance of axonal growth in vivo. Of particular importance is the ability to recreate innervation of distant brain regions by transplant tissue, for instance rebuilding the nigrostriatal track, one focus in Parkinson's disease research. Many strategies have utilized polymer drug delivery to target NF release in space and time, but combinatorial approaches are needed to deliver multiple NFs at relevant therapeutic times and locations without toxic side effects. Here we engineered a paradigm of PLGA microparticles entrapped within a degradable PEG-based hydrogel device to locally release two different types of NFs with two different release profiles. Hydrogel/microparticle devices were developed and analyzed for their ability to release GDNF in the caudal area of the brain, near the substantia nigra, or BDNF in the rostral area, near the striatum. The devices delivered their respective NFs in a region localized to within 100 μm of the bridge, but not exclusively to the targeted rostral or caudal ends. BDNF was slowly released over a 56-day period, whereas a bolus of GDNF was released around 28 days. The timed delivery of NFs from implanted devices significantly reduced the microglial response relative to sham surgeries. Given the coordinated drug delivery ability and reduced localized inflammatory response, this multifaceted PEG hydrogel/PLGA microparticle strategy may be a useful tool for further development in combining tissue engineering and drug delivery, and recreating the nigrostriatal track. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011. PMID: 21254391 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Controlling the porosity of fibrous scaffolds by modulating the fiber diameter and packing density. J Biomed Mater Res A. 2011 Mar;96(3):566-74 Authors: Soliman S, Sant S, Nichol JW, Khabiry M, Traversa E, Khademhosseini A Porosity has been shown to be a key determinant of the success of tissue engineered scaffolds. A high degree of porosity and an appropriate pore size are necessary to provide adequate space for cell spreading and migration as well as to allow for proper exchange of nutrients and waste between the scaffold and the surrounding environment. Electrospun scaffolds offer an attractive approach for mimicking the natural extracellular matrix (ECM) for tissue engineering applications. The efficacy of electrospinning is likely to depend on the interaction between cells and the geometric features and physicochemical composition of the scaffold. A major problem in electrospinning is the tendency of fibers to accumulate densely, resulting in poor porosity and small pore size. The porosity and pore sizes in the electrospun scaffolds are mainly dependent on the fiber diameter and their packing density. Here we report a method of modulating porosity in three dimensional (3D) scaffolds by simultaneously tuning the fiber diameter and the fiber packing density. Nonwoven poly(ε-caprolactone) mats were formed by electrospinning under various conditions to generate sparse or highly dense micro- and nanofibrous scaffolds and characterized for their physicochemical and biological properties. We found that microfibers with low packing density resulted in improved cell viability, proliferation and infiltration compared to tightly packed scaffolds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21254388 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Angiogenesis and osteogenesis enhanced by bFGF ex vivo gene therapy for bone tissue engineering in reconstruction of calvarial defects. J Biomed Mater Res A. 2011 Mar;96(3):543-51 Authors: Qu D, Li J, Li Y, Gao Y, Zuo Y, Hsu Y, Hu J Reconstruction of bone defects by tissue engineered substitutes requires coordinated coupling between osteogenesis and angiogenesis. Basic fibroblast growth factor (bFGF or FGF-2) is a protein which acts actively in osteogenesis and angiogenesis during skeletal healing and development. It is hypothesized that BMSCs transfected with bFGF can directly stimulate regeneration of vascular tissue, and subsequently enhance osseous formation and remodeling after implantation of the tissue engineered bone. This study was designed to examine the impact of bFGF-BMSCs, seeded on nano-hydroxyapatite/polyamide66 (n-HA/PA66) composite scaffold, to enhance angiogenesis and osteogenesis in a calvarial critical-sized defect model in rats. To investigate the vascularization and bone formation of tissue engineered bone, the substrate was removed and processed for immunohistochemical, scanning electron microscopic examinations (SEM), reverse transcriptase-polymerase chain reaction (RT-PCR), dual energy X-ray absorptiometry (DEXA), microvessels counting, and new bone volume assay. The results demonstrate that bFGF mediated ex vivo gene transfer based on BMSCs can accelerate vascularization and bone regeneration on these composite scaffolds. The n-HA/PA66 scaffold combined with the bFGF-BMSCs may mimic the natural process of osteogenesis during repair of defect by tissue engineered bone. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21254386 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Influence of polysaccharide composition on the biocompatibility of pullulan/dextran-based hydrogels. J Biomed Mater Res A. 2011 Mar;96(3):535-42 Authors: Abed A, Assoul N, Ba M, Derkaoui SM, Portes P, Louedec L, Flaud P, Bataille I, Letourneur D, Meddahi-Pellé A The implantation of a biomaterial for tissue engineering requires the presence of a suitable scaffold on which the tissue repair and regeneration will take place. Polymers have been frequently used for that purpose because they show similar properties to that of the natural extracellular matrix. Scaffold properties and biocompatibility are modulated by the composition of the polymers used. In this work four polysaccharide-based hydrogels (PSH) made of dextran and pullulan were synthesized. Their in vitro properties were determined and then tested in vivo in a rat model. As pullulan concentration increased in dextran hydrogels, the glass transition temperature and the maximum modulus decreased. In vitro degradation studies for 30 days demonstrated no significant degradation of PSH except for 100% pullulan hydrogel. In vivo tissue response evaluated 30 days after PSH subcutaneous implantation in rats indicated that all PSH were surrounded by a fibrous capsule. Adding pullulan to dextran induced an increased inflammatory reaction compared to PSH-D (100% dextran) or PSH-D(75) P(25) (75% dextran)(.) This in vitro and in vivo data can be used in the design of hydrogels appropriate for tissue engineering applications © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21254385 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | PLGA-chitosan/PLGA-alginate nanoparticle blends as biodegradable colloidal gels for seeding human umbilical cord mesenchymal stem cells. J Biomed Mater Res A. 2011 Mar;96(3):520-7 Authors: Wang Q, Jamal S, Detamore MS, Berkland C The natural polymers chitosan and alginate represent an attractive material choice for biodegradable inplants. These were used as coating materials to make positively and negatively charged PLGA nanoparticles, respectively. After blending at total solids concentration >10% wt/vol, these oppositely charged nanoparticles yielded a cohesive colloidal gel. Electrostatic forces between oppositely charged nanoparticles produced a stable 3D porous network that may be extruded or molded to the desired shape. This high concentration colloidal system demonstrated shear-thinning behavior due to the disruption of interparticle interactions. Once the external force was removed, the cohesive property of the colloidal gel was recovered. Scanning electron micrographs of dried colloidal networks revealed an organized, 3D microporous structure. Rheological studies were employed to probe the differences in plasticity and shear sensitivity of colloidal gels. Viability tests of hUCMSCs seeded on the colloidal gels also demonstrated the negligible cytotoxicity of the materials. All the results indicated the potential application of the biodegradable colloidal gels as an injectable scaffold in tissue engineering and drug release. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21254383 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cooperation of biological and mechanical signals in cardiac progenitor cell differentiation. Adv Mater. 2011 Jan 25;23(4):514-8 Authors: Pagliari S, Vilela-Silva AC, Forte G, Pagliari F, Mandoli C, Vozzi G, Pietronave S, Prat M, Licoccia S, Ahluwalia A, Traversa E, Minieri M, Di Nardo P PMID: 21254254 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Comparison of beneficial effects of undifferentiated cultured bone marrow stromal cells and omental adipose-derived nucleated cell fractions on sciatic nerve regeneration. Muscle Nerve. 2011 Feb;43(2):157-63 Authors: Mohammadi R, Azizi S, Delirezh N, Hobbenaghi R, Amini K Adipose tissue is a good source for isolation of cells with stem-cell-like properties. The effects of undifferentiated cultured bone marrow stromal cells (BMSCs) and omental adipose-derived nucleated cells (OADNCs) on peripheral nerve regeneration were compared in a rat nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a vein graft. In one group, the vein was filled with BMSCs and in the other group with OADNCs. Functional study, morphometric indices, and immunohistochemistry indicated there was no significant difference (P > 0.05) between groups in recovery of regenerated axons at 4, 8, and 12 weeks after surgery. OADNCs enhanced regeneration similar to undifferentiated BMSCs. These observations suggest OADNCs represent an effective and cost-saving cell population due to the shortened time interval from tissue collection to cell injection as well as procedural simplicity. This approach is clinically translatable toward new methods for enhanced peripheral nerve repair without the limitations of BMSC. Muscle Nerve, 2011. PMID: 21254077 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation. Biomech Model Mechanobiol. 2011 Jan 21; Authors: Maul TM, Chew DW, Nieponice A, Vorp DA Mesenchymal stem cell (MSC) therapy has demonstrated applications in vascular regenerative medicine. Although blood vessels exist in a mechanically dynamic environment, there has been no rigorous, systematic analysis of mechanical stimulation on stem cell differentiation. We hypothesize that mechanical stimuli, relevant to the vasculature, can differentiate MSCs toward smooth muscle (SMCs) and endothelial cells (ECs). This was tested using a unique experimental platform to differentially apply various mechanical stimuli in parallel. Three forces, cyclic stretch, cyclic pressure, and laminar shear stress, were applied independently to mimic several vascular physiologic conditions. Experiments were conducted using subconfluent MSCs for 5 days and demonstrated significant effects on morphology and proliferation depending upon the type, magnitude, frequency, and duration of applied stimulation. We have defined thresholds of cyclic stretch that potentiate SMC protein expression, but did not find EC protein expression under any condition tested. However, a second set of experiments performed at confluence and aimed to elicit the temporal gene expression response of a select magnitude of each stimulus revealed that EC gene expression can be increased with cyclic pressure and shear stress in a cell-contact-dependent manner. Further, these MSCs also appear to express genes from multiple lineages simultaneously which may warrant further investigation into post-transcriptional mechanisms for controlling protein expression. To our knowledge, this is the first systematic examination of the effects of mechanical stimulation on MSCs and has implications for the understanding of stem cell biology, as well as potential bioreactor designs for tissue engineering and cell therapy applications. PMID: 21253809 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Reprogramming of Sheep Fibroblasts into Pluripotency under a Drug-Inducible Expression of Mouse-Derived Defined Factors. PLoS One. 2011;6(1):e15947 Authors: Li Y, Cang M, Lee AS, Zhang K, Liu D Animal embryonic stem cells (ESCs) provide powerful tool for studies of early embryonic development, gene targeting, cloning, and regenerative medicine. However, the majority of attempts to establish ESC lines from large animals, especially ungulate mammals have failed. Recently, another type of pluripotent stem cells, known as induced pluripotent stem cells (iPSCs), have been successfully generated from mouse, human, monkey, rat and pig. In this study we show sheep fibroblasts can be reprogrammed to pluripotency by defined factors using a drug-inducible system. Sheep iPSCs derived in this fashion have a normal karyotype, exhibit morphological features similar to those of human ESCs and express AP, Oct4, Sox2, Nanog and the cell surface marker SSEA-4. Pluripotency of these cells was further confirmed by embryoid body (EB) and teratoma formation assays which generated derivatives of all three germ layers. Our results also show that the substitution of knockout serum replacement (KSR) with fetal bovine serum in culture improves the reprogramming efficiency of sheep iPSCs. Generation of sheep iPSCs places sheep on the front lines of large animal preclinical trials and experiments involving modification of animal genomes. PMID: 21253598 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Development of bioartificial myocardium using stem cells and nanobiotechnology templates. Cardiol Res Pract. 2010;2011:806795 Authors: Chachques JC Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases. PMID: 21253535 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Bone marrow-derived mesenchymal stem cells: current and future applications in the urinary bladder. Stem Cells Int. 2011;2010:765167 Authors: Drzewiecki BA, Thomas JC, Tanaka ST Mesenchymal stem cells can be isolated from almost any adult tissue. In this paper we focus on bone marrow-derived mesenchymal stem cells which have captured the interest of researchers since their introduction because of the promising potential of tissue regeneration and repair. They are known for their ability to self-renew and differentiate into diverse lineages while maintaining low immunogenicity. The exact mechanisms behind how these cells work still remain unclear, and there is a continuing shift in the paradigms that support them. There has been extensive research in multiple organ systems; however, the genitorurinary system has been vastly underrepresented. This article discusses the background behind bone marrow-derived mesenchymal stem cells and they are currently being applied to the urinary bladder in the realm of tissue engineering. We also postulate on their future applications based on the current literature in other organ systems. PMID: 21253479 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nat Rev Mol Cell Biol. 2011 Feb;12(2):79-89 Authors: Jopling C, Boue S, Izpisua Belmonte JC The ultimate goal of regenerative medicine is to replace lost or damaged cells. This can potentially be accomplished using the processes of dedifferentiation, transdifferentiation or reprogramming. Recent advances have shown that the addition of a group of genes can not only restore pluripotency in a fully differentiated cell state (reprogramming) but can also induce the cell to proliferate (dedifferentiation) or even switch to another cell type (transdifferentiation). Current research aims to understand how these processes work and to eventually harness them for use in regenerative medicine. PMID: 21252997 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | INTESTINAL MYOFIBROBLASTS: TARGETS FOR STEM CELL THERAPY. Am J Physiol Gastrointest Liver Physiol. 2011 Jan 20; Authors: Mifflin RC, Pinchuk IV, Saada JI, Powell DW The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine, and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several alpha-smooth muscle actin-positive (α-SMA) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cell or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment following injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD). PMID: 21252048 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis and analysis of degradation, mechanical, and toxicity properties of Poly(β-amino ester) degradable hydrogels. Acta Biomater. 2011 Jan 17; Authors: Hawkins AM, Milbrandt TA, Puleo DA, Hilt JZ Biodegradable hydrogels have been studied extensively in recent years for biomedical applications, including tissue engineering and drug delivery, due to their tunable properties and similarities to natural soft tissue. In this work, two poly(β-amino ester) biodegradable hydrogel systems were synthesized and studied in vitro. Different degradation profiles were observed, ranging from 7 hours to 4 months, and the compressive modulus was shown to decrease as degradation proceeded. MTT cytotoxicity analysis was used to analyze the cellular response to the degradation products, and the hydrogel systems exhibited similar toxicity to PLGA degradation products. Finally, cell attachment was studied by seeding pluripotent mesenchymal cells directly onto the hydrogel surfaces followed by a live/dead assay and fluorescent imaging. Cells showed significant viability at 24 hours (98%) and slightly lower, but still substantial viability, at 48 hours (72%). These hydrogels exhibited a range of properties and favorable cellular responses, all which indicate that these materials could be viable materials for tissue regeneration and other biomedical applications. PMID: 21252001 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | We have got you 'covered': how the meninges control brain development. Curr Opin Genet Dev. 2011 Jan 18; Authors: Siegenthaler JA, Pleasure SJ The meninges have traditionally been viewed as specialized membranes surrounding and protecting the adult brain from injury. However, there is increasing evidence that the fetal meninges play important roles during brain development. Through the release of diffusible factors, the meninges influence the proliferative and migratory behaviors of neural progenitors and neurons in the forebrain and hindbrain. Meningeal cells also secrete and organize the pial basement membrane (BM), a critical anchor point for the radially oriented fibers of neuroepithelial stem cells. With its emerging role in brain development, the potential that defects in meningeal development may underlie certain congenital brain abnormalities in humans should be considered. In this review, we will discuss what is known about assembly of the fetal meninges and review the role of meningeal-derived proteins in mouse and human brain development. PMID: 21251809 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Silk fibroin in ocular tissue reconstruction. Biomaterials. 2011 Jan 18; Authors: Harkin DG, George KA, Madden PW, Schwab IR, Hutmacher DW, Chirila TV The silk structural protein fibroin displays potential for use in tissue engineering. We present here our opinion of its value as a biomaterial for reconstructing tissues of clinical significance within the human eye. We review the strengths and weaknesses of using fibroin in those parts of the eye that we believe are most amenable to cellular reconstruction, namely the corneoscleral limbus, corneal stroma, corneal endothelium and outer blood-retinal barrier (Ruysch's complex). In these areas we find that by employing the range of manufacturing products afforded by fibroin, relevant structural assemblies can be made for cells expanded ex vivo. Significant questions now need to be answered concerning the effect of this biomaterial on the phenotype of key cell types and the biocompatibility of fibroin within the eye. We conclude that fibroin's strength, structural versatility and potential for modification, combined with the relative simplicity of associated manufacturing processes, make fibroin a worthy candidate for further exploration. PMID: 21251709 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cultivation and recovery of vascular endothelial cells in microchannels of a separable micro-chemical chip. Biomaterials. 2011 Jan 18; Authors: Yamashita T, Tanaka Y, Idota N, Sato K, Mawatari K, Kitamori T Various micro cell culture systems have recently been developed. However, it is extremely difficult to recover cultured cells from a microchannel because the upper and lower substrates of a microchip are permanently combined. Therefore, we developed a cell culture and recovery system that uses a separable microchip with reversible combining that allows separation between closed and open channels. To realize this system, two problems related to microfluidic control-prevention of leakage and non-invasive recovery of cultured cells from the substrate-must be overcome. In the present study, we used surface chemistry modification to solve both problems. First, octadecyltrimethoxysilane (ODTMS) was utilized to control the Laplace pressure at the liquid/vapor phase interface, such that it was directed toward the microchannels, which suppressed leakage from the slight gap between two substrates. Second, a thermoresponsive polymer poly(N-isopropyl acrylamide) (PNIPAAm) was used to coat the surface of the ODTMS-modified microchannel by UV-mediated photopolymerization. PNIPAAm substrates are well known for controlled cell adhesion/detachment by alteration of temperature. Finally, the ODTMS- and PNIPAAm-modified separable microchips were subjected to patterning, and human arterial endothelial cells (HAECs) were cultured in the resulting microchannels with no leakage. After 96 h of the culture, the HAECs were detached from the microchips by decreasing the temperature and were then recovered from the microchannels. This study is the first to demonstrate the recovery of living cells cultured in a microchannel, and may be useful as a fundamental technique for vascular tissue engineering. PMID: 21251708 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human Acute Myelogenous Leukemia Stem Cells Revisited: There's More Than Meets the Eye. Cancer Cell. 2011 Jan 18;19(1):9-10 Authors: Majeti R, Weissman IL In this issue of Cancer Cell, Goardon et al. revise earlier conclusions regarding acute myelogenous leukemia (AML) stem cells by demonstrating that in the majority of patients, they reside in two hierarchically related populations most similar to normal hematopoietic progenitors. These findings have implications for therapeutic targeting of these cells. PMID: 21251611 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | BONE REGENERATION: STEM CELL THERAPIES AND CLINICAL STUDIES IN ORTHOPAEDICS AND TRAUMATOLOGY. J Cell Mol Med. 2011 Jan 20; Authors: Gómez-Barrena E, Rosset P, Müller I, Giordano R, Bunu C, Layrolle P, Konttinen YT, Luyten FP Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells (MSC), good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products (ATMP), the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. PMID: 21251219 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cyclic ADP ribose is a novel regulator of intracellular Ca(2+) oscillations in human bone marrow mesenchymal stem cells. J Cell Mol Med. 2011 Jan 20; Authors: Tao R, Sun HY, Lau CP, Tse HF, Lee HC, Li GR Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for regenerative medicine. However, the cellular biology of these cells is not fully understood. The present study characterizes the cyclic ADP-ribose (cADPR)-mediated Ca(2+) signals in human MSCs and finds that externally applied cADPR can increase the frequency of spontaneous intracellular Ca(2+) (Ca(2+) (i) ) oscillations. The increase was abrogated by a specific cADPR antagonist or an IP3Rs inhibitor, but not by ryanodine. In addition, the cADPR-induced increase of Ca(2+) (i) oscillation frequency was prevented by inhibitors of nucleoside transporter or by inhibitors of the TRPM2 channel. RT-PCR revealed mRNAs for the nucleoside transporters, CNT1/2 and ENT1/3, IP3R1/2/3, and the TRPM2 channel, but not those for RyRs and CD38 in human MSCs. Knock-down of the TRPM2 channel by specific siRNA abolished the effect of cADPR on the Ca(2+) (i) oscillation frequency, and prevented the stimulation of proliferation by cADPR. Moreover, cADPR remarkably increased phosphorylated ERK1/2, but not Akt or p38 MAPK. However, cADPR had no effect on adipogenesis or osteogenesis in human MSCs. Our results indicate that cADPR is a novel regulator of Ca(2+) (i) oscillations in human MSCs. It permeates the cell membrane through the nucleoside transporters and increases Ca(2+) oscillation via activation of the TRPM2 channel, resulting in enhanced phosphorylation of ERK1/2 and, thereby, stimulation of hMSC proliferation. This study delineates an alternate signaling pathway of cADPR that is distinct from its well established role of serving as a Ca(2+) messenger for mobilizing the internal Ca(2+) stores. Whether cADPR can be used clinically for stimulating marrow function in patients with marrow disorders remains further studied. PMID: 21251217 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of Exon-Skipping Strategies for Duchenne Muscular Dystrophy Utilizing Dystrophin-deficient Zebrafish. J Cell Mol Med. 2011 Jan 20; Authors: Berger J, Berger S, Jacoby AS, Wilton SD, Currie PD Duchenne Muscular Dystrophy is a severe muscle wasting disease caused by mutations in the dystrophin gene. By utilising antisense oligonucleotides, splicing of the dystrophin transcript can be altered so that exons harbouring a mutation are excluded from the mature mRNA. While this approach has been shown to be effective to restore partially functional dystrophin protein, the level of dystrophin protein that is necessary to rescue a severe muscle pathology has not been addressed. As zebrafish dystrophin mutants (dmd) resemble the severe muscle pathology of human patients, we have utilised this model to evaluate exon-skipping. Novel dmd mutations were identified to enable the design of phenotype rescue studies via morpholino administration. Correlation of induced exon-skipping efficiency and the level of phenotype rescue suggests that relatively robust levels of exon-skipping are required to achieve significant therapeutic ameliorations and that pre-screening analysis of exon-skipping drugs in zebrafish may help to more accurately predict clinical trials for therapies of Duchenne Muscular Dystrophy. PMID: 21251213 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Recombinant human HGF, but not rat HGF, elicits glomerular injury and albuminuria in normal rats via an immune complex-dependent mechanism. Clin Exp Pharmacol Physiol. 2011 Jan 20; Authors: Mizuno S, Ikebuchi F, Fukuta K, Kato T, Matsumoto K, Adachi K, Nakamura T Hepatocyte growth factor (HGF) has the therapeutic potential to improve renal fibrosis and proteinuria in rodents with chronic kidney disease. By contrast, long-term administration of human HGF to normal rats reportedly elicits proteinuria. Thus, the role of HGF during proteinuria remains controversial. The aim of the present study is to demonstrate that human HGF is antigenic to rodents and that immune complex formation causes proteinuria. We administered either human HGF or rat HGF to normal rats for 28 days. Albuminuria was evaluated by SDS-PAGE. The renal phenotypes of the two HGF treatments were examined using histological techniques. Administration of human HGF (1 mg/kg/day, i.v.) to rats led to severe albuminuria and glomerular hypertrophy in association with increased blood levels of anti-human HGF IgG and IgG deposition in mesangial areas. Furthermore, an immune complex between human HGF and anti-human HGF IgG stimulated the production of proteinuric cytokines (including transforming growth factor-β) in rat cultured mesangial cells. By contrast, treatment of healthy rats with rat HGF for 4 weeks caused neither mesangial IgG deposition nor elevated anti-HGF IgG in blood. Overall, rat HGF did not provoke albuminuria. We conclude that human HGF produces pseudo-toxic effects in normal rat kidneys via an immune complex-mediated pathway, while syngenic HGF is safe due to less deposition of glomerular IgG. Our results affirm the safety of the repeated use of syngenic HGF for the treatment of chronic organ diseases, such as renal fibrosis and liver cirrhosis. PMID: 21251050 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Global transcriptome analysis of human bone marrow stromal cells (BMSC) reveals proliferative, mobile and interactive cells that produce abundant extracellular matrix proteins, some of which may affect BMSC potency. Cytotherapy. 2011 Jan 20; Authors: Ren J, Jin P, Sabatino M, Balakumaran A, Feng J, Kuznetsov SA, Klein HG, Robey PG, Stroncek DF Abstract Background aims. Bone marrow stromal cells (BMSC) are being used for immune modulatory, anti-inflammatory and tissue engineering applications, but the properties responsible for these effects are not completely understood. Human BMSC were characterized to identify factors that might be responsible for their clinical effects and biomarkers for assessing their quality. Methods. Early passage BMSC prepared from marrow aspirates of seven healthy subjects were compared with three human embryonic stem cell (hESC) samples, CD34(+) cells from three healthy subjects and three fibroblast cell lines. The cells were analyzed with oligonucleotide expression microarrays with more than 35 000 probes. Results. BMSC gene expression signatures of BMSC differed from those of hematopoietic stem cells (HSC), hESC and fibroblasts. Genes upregulated in BMSC were involved with cell movement, cell-to-cell signaling and interaction and proliferation. The upregulated genes most probably belonged to pathways for integrin signaling, integrin-linked kinase (ILK) signaling, NF-E2-related factor-2 (NFR2)-mediated oxidative stress response, regulation of actin-based motility by Rho, actin cytoskeletal signaling, caveolar-mediated endocytosis, clathrin-mediated endocytosis and Wingless-type MMTV integration site (Wnt/β catenin signaling. Among the most highly upregulated genes were structural extracellular matrix (ECM) proteins (α5 and β5 integrin chains, fibronectin and collagen type IIIα1 and Vα1) and functional EMC proteins [connective tissue growth factor (CTGF), transforming growth factor beta-induced protein (TGFBI) and A disintegrin and metalloproteinase (ADAM12)]. Conclusions. Global analysis of human BMSC suggests that they are mobile, metabolically active, proliferative and interactive cells that make use of integrins and integrin signaling. They produce abundant ECM proteins that may contribute to their clinical immune modulatory and anti-inflammatory effects. PMID: 21250865 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Successful periodontal ligament regeneration by periodontal progenitor pre-seeding on natural tooth root surfaces. Stem Cells Dev. 2011 Jan 21; Authors: Dangaria SJ, Ito Y, Luan X, Diekwisch TG The regeneration of lost periodontal ligament and alveolar bone is the purpose of periodontal tissue engineering. The goal of the present study was to assess the suitability of three odontogenic progenitor populations from dental pulp (DP), periodontal ligament (PDL), and dental follicle (DF) for periodontal regeneration when exposed to natural and synthetic apatite surface topographies. We demonstrated that PDL progenitors featured higher levels of periostin and scleraxis expression, increased adipogenic and osteogenic differentiation potential, and pronounced elongated cell shapes on barren root chips when compared to DP and DF cells. When evaluating the effect of surface characteristics on PDL progenitors, natural root surfaces resulted in elongated PDL cell shapes, while PDL progenitors on synthetic apatite surfaces were rounded or polygonal. In addition, surface coatings affected PDL progenitor gene expression profiles: collagen I coatings enhanced alkaline phosphatase and osteocalcin expression levels and laminin-1 coatings increased EGF, nestin, cadherin 1, and keratin 8 expression. PDL progenitors seeded on natural tooth root surfaces in organ culture formed new periodontal fibers after three weeks culture. Finally, replantation of PDL progenitor-seeded tooth roots into rat alveolar bone sockets resulted in the complete formation of a new periodontal ligament and stable re-attachment of teeth over a six month period. Together, these findings indicate that periodontal progenitor cell type as well as mineral surface topography and molecular environment play crucial roles in the regeneration of true periodontal anchorage. PMID: 21250830 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Molecular and cellular characterization of expanded and cryopreserved human limbal epithelial stem cells reveal unique immunological properties. Exp Eye Res. 2011 Jan;92(1):47-56 Authors: Vasania VS, Prasad P, Gill RK, Mehta A, Viswanathan C, Sarang S, Majumdar AS Transplantation of ex vivo expanded autologous limbal stem cells into the diseased eye of patients with limbal stem cell deficiency (LSCD) has been in practice worldwide. However, isolation of limbal tissue from the normal eye of the patient with unilateral LSCD still remains a major concern for the donor. More importantly, autologous cell transplantation is not a viable option for patients with bilateral LSCD. The objective of the current study was to determine the expansion potential of human limbal epithelial stem cells (hLESCs) for their possible use in allo-transplantation. A total of six limbal biopsy samples were cultured and expanded in vitro up to passage level 1 (P-1), at which point the hLESCs were cryopreserved. Semi-quantitative RT-PCR and immunophenotypic analysis revealed that hLESCs obtained before and after cryopreservation retained the expression of major limbal epithelial stem cell markers such as p63, SSEA-4, ABCG2, cytokeratin 19 (CK19), integrin β1 and vimentin. One notable difference was that while P-0 hLESCs expressed HLA-DR mRNA, no HLA-DR gene expression was observed with the expanded and cryopreserved samples. Human LESCs did not express costimulatory proteins CD80 or B7-DC but expressed significant levels of CD86, B7-H1 and HLA-ABC molecules on the cell surface. Treatment of hLESCs with IFN-γ induced the expression of HLA-DR, indoleamine 2,3-dioxygenase (IDO) and HLA-G on these cells. Cultured hLESCs were unable to stimulate allogeneic T cell proliferation in vitro even in the presence of pro-inflammatory cytokine, IFN-γ. These results indicate that cryopreserved hLESCs are non-immunogenic in nature and express negative immunoregulatory molecules which may be critical for their survival in an allogeneic environment. PMID: 21093433 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Bioreactors for development of tissue engineered heart valves. Ann Biomed Eng. 2010 Nov;38(11):3272-9 Authors: Berry JL, Steen JA, Koudy Williams J, Jordan JE, Atala A, Yoo JJ Millions of people worldwide are diagnosed each year with valvular heart disease, resulting in hundreds of thousands of valve replacement operations. Prosthetic valve replacements are designed to correct narrowing or backflow through the valvular orifice. Although commonly used, these therapies have serious disadvantages including morbidity associated with long-term anticoagulation and limited durability necessitating repeat operations. The ideal substitute would be widely available and technically implantable for most cardiac surgeons, have normal hemodynamic performance, low risk for structural degeneration, thrombo-embolism and endocarditis, and growth potential for pediatric patients. Tissue engineered heart valves hold promise as a viable substitute to outperform existing valve replacements. An essential component to the development of tissue engineered heart valves is a bioreactor. It is inside the bioreactor that the scaffold and cells are gradually conditioned to the biochemical and mechanical environment of the valve to be replaced. PMID: 20820920 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Enhancement of the ALP activity of C3H10T1/2 cells by the combination of an oxysterol and apatite. Biomed Mater. 2010 Aug;5(4):044107 Authors: Son KM, Park HC, Kim NR, Lee IS, Yang HC Biomimetic apatite coating has been used to load osteogenic biomolecules onto the surface of titanium implants. Apatite on the surface of biomaterials is thought to function as a reservoir of biomolecules as well as enhancing osteoconductivity. In this study, 20alpha-hydroxycholesterol (20alpha-HC), an osteogenic oxysterol, was used to induce differentiation of a mouse embryo fibroblast cell line (C3H10T1/2) by loading the oxysterol on biomimetically coated apatite of titanium discs. We found that the phosphatase (alkaline phosphatase (ALP)) activity of 20alpha-HC was significantly higher with ascorbic acid than alone, suggesting a need for ascorbic acid as a co-factor. When 20alpha-HC was added into the apatite coating solution, the ALP activity of the C3H10T1/2 cells did not increase on the apatite surface, even in the presence of ascorbic acid. However, ALP activity increased dramatically when 20alpha-HC was loaded by volatilization of EtOH from the apatite coat after dipping discs in 20alpha-HC-dissolved EtOH. Interestingly, ascorbic acid was not needed for this increase in ALP activity, suggesting a synergistic effect of 20alpha-HC and apatite. The concentration of calcium ions, a major component of apatite, affected the osteogenic effect of 20alpha-HC, and the increase in ALP activity was attenuated by L-type calcium channel inhibitors, verapamil and nifedipine. These results demonstrate that calcium ions released from apatite are important in the synergistic effect of 20alpha-HC and apatite. PMID: 20683129 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The biological activities of (1,3)-(1,6)-beta-d-glucan and porous electrospun PLGA membranes containing beta-glucan in human dermal fibroblasts and adipose tissue-derived stem cells. Biomed Mater. 2010 Aug;5(4):044109 Authors: Woo YI, Park BJ, Kim HL, Lee MH, Kim J, Yang YI, Kim JK, Tsubaki K, Han DW, Park JC In this study, we investigated the possible roles of (1,3)-(1,6)-beta-d-glucan (beta-glucan) and porous electrospun poly-lactide-co-glycolide (PLGA) membranes containing beta-glucan for skin wound healing, especially their effect on adult human dermal fibroblast (aHDF) and adipose tissue-derived stem cell (ADSC) activation, proliferation, migration, collagen gel contraction and biological safety tests of the prepared membrane. This study demonstrated that beta-glucan and porous PLGA membranes containing beta-glucan have enhanced the cellular responses, proliferation and migration, of aHDFs and ADSCs and the result of a collagen gel contraction assay also revealed that collagen gels contract strongly after 4 h post-gelation incubation with beta-glucan. Furthermore, we confirmed that porous PLGA membranes containing beta-glucan are biologically safe for wound healing study. These results indicate that the porous PLGA membranes containing beta-glucan interacted favorably with the membrane and the topical administration of beta-glucan was useful in promoting wound healing. Therefore, our study suggests that beta-glucan and porous PLGA membranes containing beta-glucan may be useful as a material for enhancing wound healing. PMID: 20683126 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Investigation of the cytotoxicity mechanism of silver nanoparticles in vitro. Biomed Mater. 2010 Aug;5(4):044103 Authors: Wei L, Tang J, Zhang Z, Chen Y, Zhou G, Xi T Nowadays, more and more nanotechnology products and nanomaterials are being applied in our lives. Silver nanoparticles (SNPs) are used in infection prevention and treatment due to their antimicrobial activity. However, as a kind of nanomaterial, the toxicology of SNPs has not been completely studied. The mechanism of cytotoxicity of SNPs in vitro to mouse's fibroblast cells (L929) was investigated in this study. As a contrast, silver microparticles (SMPs) were also studied. Propidium iodide (PI) single staining and Annexin-V/PI staining were carried out to unveil the influence of SNPs and SMPs on the cells. A transmission electron microscope (TEM) was used to observe SNPs' distribution in the cells. The results of cell cycle analysis indicated that the cells treated with SNPs were arrested in the G2M phase. Meanwhile, SNPs lead to apoptosis of more cells compared to SMPs at the same dose as a result of apoptosis analysis. Analysis of the cells' ultrastructure showed that SNPs could be phagocytized into the cells while SMPs could not. The mechanism of cytotoxicity of SNPs in vitro to L929 cells may be that SNPs are phagocytized into the cells and they interact with mitochondria or other organelles, even nuclei, which results in cells' apoptosis or necrosis. PMID: 20683123 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |  | |  | |  |
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