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| Biocompatibility of KLD-12 peptide hydrogel as a scaffold in tissue engineering of intervertebral discs in rabbits.
April 22, 2010 at 8:17 AM
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| | Biocompatibility of KLD-12 peptide hydrogel as a scaffold in tissue engineering of intervertebral discs in rabbits. J Huazhong Univ Sci Technolog Med Sci. 2010 Apr;30(2):173-7 Authors: Sun J, Zheng Q, Wu Y, Liu Y, Guo X, Wu W KLD-12 peptide with a sequence of AcN-KLDLKLDLKLDL-CNH(2) was synthesized and its biocompatibility was assessed in animals. Rabbit MSCs were cultured in the hydrogel for 2 weeks. Live cells were counted by using Calcein-AM/PI fluorescence staining. MTT was employed to assess the viability of MSCs cultured in KLD-12 peptide solution of 0.01%, 0.03%, and 0.05%. Hemolysis test, skin irritation test and implantation test were conducted to evaluate its biocompatibility with host tissues. Our results demonstrated that the MSCs in hydrogel grew well and maintained round shape. Cell survival rate was 92.15% (mean: 92.15%+/-1.17%) at the 7th day and there was no difference in survival rate between day 7 and day 14. Cell proliferation test showed that the A value of the KLD-12 solutions was not significantly different from that of control groups (complete culture media) (P>0.05) at the 24th and 48th h. The hemolysis rate of KLD-12 solution was 0.112%. Skin irritation tes! t showed that the skin injected with KLD-12 solution remained normal and the score of skin irritation was 0. The histological examination with HE staining exhibited that the skin layers were clear and there was no infiltration with neutrophilic granulocytes and lymphocytes. It is concluded that KLD-12 peptide hydrogel had a good biocompatibility with host rabbit and MSCs, and KLD-12 peptide hydrogel can provide an appropriate microenvironment for MSCs. PMID: 20407868 [PubMed - in process] | | |
| Proteomic profiling of human bone marrow mesenchymal stem cells under shear stress.
April 22, 2010 at 8:17 AM
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| | Proteomic profiling of human bone marrow mesenchymal stem cells under shear stress. Mol Cell Biochem. 2010 Apr 21; Authors: Yi W, Sun Y, Wei X, Gu C, Dong X, Kang X, Guo S, Dou K Mesenchymal stem cells (MSCs) are promising seed cells for tissue engineering of blood vessels. As seed cells, MSCs must endure blood fluid shear stress after transplantation. It has been shown that fluid shear stress can regulate the proliferation and differentiation of MSCs. However, the effects of fluid shear stress on MSCs including the types of proteins modulated are still not well understood. In this study, we exposed human mesenchymal stem cells (HMSCs) to 3 dyn/cm(2) shear stress for 6 h and compared them to a control group using proteomic analysis. Thirteen specific proteins were affected by shear stress, 10 of which were up-regulated. Shear stress especially induced sustained increases in the expression of Annexin A2 and GAPDH, which have been specifically shown to affect HMSCs function. We present here the first comparative proteome analysis of effect of shear stress on HMSCs. PMID: 20407807 [PubMed - as supplied by publisher] | | |
| Characterisation and testing of biomaterials.
April 22, 2010 at 8:17 AM
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| | Characterisation and testing of biomaterials. Stud Health Technol Inform. 2010;152:231-46 Authors: Dendorfer S, Hammer J, Lenich A A proper knowledge of the mechanical and material properties of biomaterials is a necessity in all medical device technologies: from tissue engineering to prosthesis design. In many cases, the design of novel biomaterials is governed by the mechanical properties and their characterisation may become a crucial factor in determining the success of a product. This chapter discusses the basic concepts of the characterisation and testing of materials. Starting from the fundamental concepts of elastic, viscoelastic and plastic deformation, an introduction to experimental methods is given. The special limitations and requirements set by biomaterials are discussed. PMID: 20407198 [PubMed - in process] | | |
| Bioreactors in tissue engineering.
April 22, 2010 at 8:17 AM
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| | Bioreactors in tissue engineering. Stud Health Technol Inform. 2010;152:214-30 Authors: Plunkett N, O'Brien FJ A bioreactor can be defined as a device that uses mechanical means to influence biological processes. In tissue engineering bioreactors can be used to aid in the in vitro development of new tissue by providing biochemical and physical regulatory signals to cells and encouraging them to undergo differentiation and/or to produce extracellular matrix prior to in vivo implantation. This chapter discusses the necessity for bioreactors in tissue engineering, the numerous types of bioreactor that exist, the means by which they stimulate cells and how their functionality is governed by the requirements of the specific tissue being engineered and the cell type undergoing stimulation. PMID: 20407197 [PubMed - in process] | | |
| Scaffolds & surfaces.
April 22, 2010 at 8:17 AM
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| | Scaffolds & surfaces. Stud Health Technol Inform. 2010;152:187-201 Authors: Partap S, Lyons F, O'Brien FJ As the field of regenerative medicine progresses, one of the key challenges is to try to mimic the structure and role of the natural extracellular matrix (ECM) more accurately in synthetic substitutes. In particular, the field of biomaterials has played a crucial role in the development of tissue engineered products. Scaffold design is central in the field of biomaterials, and involves investigating and controlling important characteristics such as biocompatibility, degradability, pore architecture and mechanical properties. Undoubtedly, we will move closer towards reducing the number of patients awaiting donor tissues, as more advanced biomaterials continue to be developed in this field. This chapter discusses scaffold requirements for tissue engineering applications and the current state of the art with a specific focus on collagen-based scaffolds. PMID: 20407195 [PubMed - in process] | | |
| Human embryonic stem cell-derived cardiomyocytes: demonstration of a portion of cardiac cells with fairly mature electrical phenotype.
April 22, 2010 at 8:17 AM
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| | Human embryonic stem cell-derived cardiomyocytes: demonstration of a portion of cardiac cells with fairly mature electrical phenotype. Exp Biol Med (Maywood). 2010 Apr 1;235(4):522-30 Authors: Pekkanen-Mattila M, Chapman H, Kerkelä E, Suuronen R, Skottman H, Koivisto AP, Aalto-Setälä K Cardiomyocytes (CMs) derived from human embryonic stem cells (hESC) provide a promising tool for the pharmaceutical industry. In this study the electrical properties and maturation of hESC-CM derived using two differentiation methods were compared and the suitability of hESC-CMs as a cell model for the assessment of drug-induced repolarization delay was evaluated. CMs were differentiated either in END-2 co-culture or by spontaneous differentiation. Action potentials (APs) were recorded from cells in spontaneously beating areas using the whole-cell patch-clamp technique. The hESC-CMs exhibited predominantly a ventricular-like phenotype with heterogeneous properties. Heterogeneity was indicative of the spectrum of hESC-CM maturation from embryonic-like with AP upstroke velocities <30 V/s and maximum diastolic potential (MDP) of close to -60 mV to more mature with values >150 V/s and -80 mV, respectively. The mean MDP was -70 mV and a significant difference was! observed between the two differentiation methods (-66 versus -75 mV, P < 0.001). The age of the CMs did not correlate with phenotype maturation. The addition of the hERG blocker E-4031 and the sodium channel modulator veratridine significantly prolonged the AP duration. Furthermore, proarrhythmic indices were induced. In conclusion, the main observation was the heterogeneity in electrical properties of the hESC-CMs and this was observed with both differentiation methods. One-third of the hESC-CMs exhibited fairly mature electrophysiological properties, suggesting that mature CMs could be obtained from hESCs. However, improved differentiation methods are needed to produce homogeneous mature human CMs for pharmaceutical and toxicological applications. PMID: 20407085 [PubMed - in process] | | |
| Direct Activation of Emmprin and Associated Pathogenesis by an Oncogenic Herpesvirus.
April 22, 2010 at 8:17 AM
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| | Direct Activation of Emmprin and Associated Pathogenesis by an Oncogenic Herpesvirus. Cancer Res. 2010 Apr 20; Authors: Qin Z, Dai L, Slomiany MG, Toole BP, Parsons C Emmprin (extracellular matrix metalloproteinase inducer) is a multifunctional glycoprotein expressed by cancer cells and stromal cells in the tumor microenvironment. Through both direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin induces tumor cell invasiveness and regional angiogenesis. The Kaposi's sarcoma-associated herpesvirus (KSHV) is a common etiology for cancers arising in the setting of immune suppression, including Kaposi's sarcoma and primary effusion lymphoma. However, whether emmprin expression and function are regulated by KSHV or other oncogenic viruses in the tumor microenvironment to promote viral cancer pathogenesis remains unknown. Fibroblasts and endothelial cells support latent KSHV infection and represent cellular components of Kaposi's sarcoma lesions. Therefore, we used primary human fibroblasts and endothelial cells to determine whether KSHV itself regulates emmprin expression, and whether KSHV-emmprin in! teractions mediate cell invasiveness. We found that KSHV promotes fibroblast and endothelial cell invasiveness following de novo infection through the upregulation of emmprin, and that this effect is mediated by the KSHV-encoded latency-associated nuclear antigen. We also found that emmprin promotes invasiveness, as well as colony formation, by primary effusion lymphoma cells derived from human tumors. Collectively, these data implicate KSHV activation of emmprin as an important mechanism for cancer progression and support the potential utility of targeting emmprin as a novel therapeutic approach for KSHV-associated tumors. Cancer Res; 70(10); OF1-6. (c)2010 AACR. PMID: 20406987 [PubMed - as supplied by publisher] | | |
| Disruption of a Quorum Sensing mechanism triggers tumorigenesis: a simple discrete model corroborated by experiments in mammary cancer stem cells.
April 22, 2010 at 8:17 AM
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| | Disruption of a Quorum Sensing mechanism triggers tumorigenesis: a simple discrete model corroborated by experiments in mammary cancer stem cells. Biol Direct. 2010 Apr 20;5(1):20 Authors: Agur Z, Kogan Y, Levi L, Harrison H, Lamb R, Kirnasovsky OU, Clarke RB ABSTRACT: BACKGROUND: The balance between self-renewal and differentiation of stem cells is expected to be tightly controlled in order to maintain tissue homeostasis throughout life, also in the face of environmental hazards. Theory, predicting that homeostasis is maintained by a negative feedback on stem cell proliferation, implies a Quorum Sensing (QS) mechanism in higher vertebrates. RESULTS: Application of this theory to a cellular automata model of stem cell development in disrupted environments shows a sharply dichotomous growth dynamics: maturation within 50-400 cell-cycles, or immortalization. This dichotomy is mainly driven by intercellular communication, low values of which cause perpetual proliferation. Another driving force is the cells' kinetic parameters. Reduced tissue life-span of differentiated cells results in uncontrolled proliferation. Model's analysis, showing that under the QS control, stem cell fraction within a steady state population is fi! xed, is corroborated by experiments in breast carcinoma cells. Experimental results show that the plating densities of CD44+ cells and of CD44+/24lo/ESA+ cells do not affect SC fraction near confluence. CONCLUSIONS: This study suggests that stem cell immortalization may be triggered by reduced intercellular communication, rather than exclusively result from somatic evolution, and implies that stem cell proliferation can be attenuated by signal manipulation, or enhanced by cytotoxics targeted to differentiated cells. In vivo verification and identification of the QS mediating molecules will pave the way to a higher level control of stem cell proliferation in cancer and in tissue engineering. Reviewers: This article was reviewed by Glenn Webb and Marek Kimmel. PMID: 20406437 [PubMed - as supplied by publisher] | | |
| Moving towards in situ tracheal regeneration: the bionic tissue engineered transplantation approach.
April 22, 2010 at 8:17 AM
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| | Moving towards in situ tracheal regeneration: the bionic tissue engineered transplantation approach. J Cell Mol Med. 2010 Apr 19; Authors: Bader A, Macchiarini P Abstract On June 2008, the world's first whole tissue-engineered organ - the windpipe - was successfully transplanted into a 31 years old lady, and about 18 months following surgery she is leading a near normal life without immunosuppression. This outcome has been achieved by employing three groundbreaking technologies of regenerative medicine: a) a donor trachea first decellularized using a detergent (without denaturing the collagenous matrix), b) the two main autologous tracheal cells, namely mesenchymal stem cell-derived cartilage-like cells and epithelial respiratory cells, c) a specifically designed bioreactor that reseed, before implantation, the in vitro preexpanded and predifferentiated cells the autologous cells on the desired surfaces of the decellularized matrix. Given the long-term safety, efficacy and efforts using such a conventional approach and the potential advantages of regenerative implants to make them available for anyone, we have investigated! a novel alternative concept how to fully avoid in vitro cell replication, expansion and differentiation, use the human native site as micro-niche, potentiate the human body's site-specific response by adding boosting, permissive and recruitment impulses in full respect of sociological and regulatory prerequisites. This tissue engineered approach and ongoing research in airway transplantation is reviewed and presented here. PMID: 20406329 [PubMed - as supplied by publisher] | | |
| The Pleotrophic Effects of IGF-I on Human Spinal Cord Neural Progenitor Cells.
April 22, 2010 at 8:17 AM
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| | The Pleotrophic Effects of IGF-I on Human Spinal Cord Neural Progenitor Cells. Stem Cells Dev. 2010 Apr 20; Authors: Lunn JS, Pacut C, Backus C, Hong Y, Johe K, Hefferan M, Feldman EL, Marsala M Most stem cell therapies involve direct, intraparachymal placement of neural progenitor cells. These cells provide physical support to the endogenous neuronal population and may be engineered to provide in situ growth factor support. Insulin-like growth factor-I (IGF-I) has potent neurotrophic and neuroprotective properties and is expressed by human neural stem cells (hNSCs). IGF-I is implicated in multiple aspects of cell behavior including proliferation, differentiation and survival. Enhancing hNSC function through IGF-I over-expression may increase the benefits of stem cell therapy. As a first step to that goal, we examined the direct effects of IGF-I on hNSC behavior in vitro. We demonstrate that IGF-I treatment enhances both the number and length of hNSC neurites. This is correlated with a decrease in proliferation, suggesting that IGF-I promotes neurite outgrowth but not proliferation. While IGF-I activates both AKT and MAPK signaling in hNSCs, we demonstrat! e that IGF-I-mediated neurite outgrowth is dependent only on AKT signaling. Finally, we demonstrate that IGF-I is neuroprotective following glutamate exposure in a model of excitotoxic cell death. PMID: 20406098 [PubMed - as supplied by publisher] | | |
| Systematic evaluation of a tissue-engineered bone for maxillary sinus augmentation in large animal canine model.
April 22, 2010 at 8:17 AM
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| | Systematic evaluation of a tissue-engineered bone for maxillary sinus augmentation in large animal canine model. Bone. 2010 Jan;46(1):91-100 Authors: Wang S, Zhang Z, Xia L, Zhao J, Sun X, Zhang X, Ye D, UludaÄŸ H, Jiang X The objective of this study is to systematically evaluate the effects of a tissue-engineered bone complex for maxillary sinus augmentation in a canine model. Twelve sinus floor augmentation surgeries in 6 animals were performed bilaterally and randomly repaired with the following 3 groups of grafts: group A consisted of tissue-engineered osteoblasts/beta-TCP complex (n=4); group B consisted of beta-TCP alone (n=4); group C consisted of autogenous bone obtained from iliac crest as a positive control (n=4). All dogs had uneventful healings following the surgery. Sequential polychrome fluorescent labeling, maxillofacial CT, microhardness tests, as well as histological and histomorphometric analyses indicated that the tissue-engineered osteoblasts/beta-TCP complex dramatically promoted bone formation and mineralization and maximally maintained the height and volume of elevated maxillary sinus. By comparison, both control groups of beta-TCP or autologous iliac bone sho! wed considerable resorption and replacement by fibrous or fatty tissue. We thus conclude that beta-TCP alone could barely maintain the height and volume of the elevated sinus floor, and that the transplantation of autogenous osteoblasts on beta-TCP could promote earlier bone formation and mineralization, maximally maintain height, volume and increase the compressive strength of augmented maxillary sinus. This tissue engineered bone complex might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation. PMID: 19761881 [PubMed - indexed for MEDLINE] | | | | 
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