|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Stem Cell Therapy for Myocardial Infarction: Are We Missing Time? Cardiology. 2010 Sep 29;117(1):1-10 Authors: Ter Horst KW The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by the acute inflammatory response on one hand and by scar formation on the other. In the meantime, microenvironmental factors must favor stem cell homing, survival, differentiation, and integration for stem cell therapy to be effective. Clinical data on the optimal timing of treatment are scarce. Experimental studies and clinical subgroup analyses can provide a clue and useful guidance for further research. In this review, the fundamental mechanisms as well as trial results important for the determination of the optimal timing of stem cell therapy following MI are summarized and discussed. We conclude that optimization of stem cell therapy requires further research on the fundamental mechanisms responsible for stem cell homing, survival, differentiation, and integration. Clinically, randomized trials with bone-marrow-derived stem cells should be conducted timing therapy at different points within the first month after MI, which seems to be the most promising period for this cell type. PMID: 20881387 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Optimization and scale-up of Wharton's jelly-derived mesenchymal stem cells for clinical applications. Stem Cell Res. 2010 Sep 27; Authors: Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S, Ta M MSCs are promising candidates for stem cell therapy and regenerative medicine. Umbilical cord is the easiest obtainable biological source of MSCs and the Wharton's jelly of the umbilical cord is a rich source of fetus-derived stem cells. However, the use of MSCs for therapeutic application is based on their subsequent large-scale in vitro expansion. A fast and efficient protocol for generation of large quantities of MSCs is required to meet the clinical demand and biomedical research needs. Here we have optimized conditions for scaling up of WJ-MSCs. Low seeding density along with basic fibroblast growth factor (bFGF) supplementation in the growth medium, which is DMEM-KO, resulted in propagation of more than 1x10(8) cells within a time period of 15days from a single umbilical cord. The upscaled WJ-MSCs retained their differentiation potential and immunosuppressive capacity. They expressed the typical hMSC surface antigens and the addition of bFGF in the culture medium did not affect the expression levels of HLA-DR and CD 44. A normal karyotype was confirmed in the large-scale expanded WJ-MSCs. Hence, in this study we attempted rapid clinical-scale expansion of WJ-MSCs which would allow these fetus-derived stem cells to be used for various allogeneic cell-based transplantations and tissue engineering. PMID: 20880767 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Intracoronary administration of autologous mesenchymal stem cells in a critically ill patient with dilated cardiomyopathy. Pediatr Transplant. 2010 Sep 29; Authors: Zeinaloo A, Zanjani KS, Bagheri MM, Mohyeddin-Bonab M, Monajemzadeh M, Arjmandnia MH Zeinaloo AA, Zanjani KS., Bagheri MM., Mohyeddin-Bonab M, Monajemzadeh M, Arjmandnia MH. Intracoronary administration of autologous mesenchymal stem cells in a critically ill patient with dilated cardiomyopathy.
Pediatr Transplantation 2010. © 2010 John Wiley & Sons A/S. Abstract:  Relatively high prevalence of dilated cardiomyopathy in children, unfavorable response to traditional drug therapy, and limitations in heart transplantation call for new therapeutic options. Stem cell therapy can be promising in children suffering from this disease. The presented case documents that intracoronary injection of autologous bone marrow-derived mesenchymal stem cells in a boy with progressive dilated cardiomyopathy is feasible and safe. Furthermore, it may positively influence functional class, quality of life, and echocardiographic indices of cardiac function. PMID: 20880092 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Advanced material strategies for tissue engineering scaffolds. Adv Mater. 2009 Sep 4;21(32-33):3410-8 Authors: Freed LE, Engelmayr GC, Borenstein JT, Moutos FT, Guilak F Tissue engineering seeks to restore the function of diseased or damaged tissues through the use of cells and biomaterial scaffolds. It is now apparent that the next generation of functional tissue replacements will require advanced material strategies to achieve many of the important requirements for long-term success. Here, we provide representative examples of engineered skeletal and myocardial tissue constructs in which scaffolds were explicitly designed to match native tissue mechanical properties as well as to promote cell alignment. We discuss recent progress in microfluidic devices that can potentially serve as tissue engineering scaffolds, since mass transport via microvascular-like structures will be essential in the development of tissue engineered constructs on the length scale of native tissues. Given the rapid evolution of the field of tissue engineering, it is important to consider the use of advanced materials in light of the emerging role of genetics, growth factors, bioreactors, and other technologies. PMID: 20882506 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering using laminar cellular assemblies. Adv Mater. 2009 Sep 4;21(32-33):3404-9 Authors: Yang J, Yamato M, Sekine H, Sekiya S, Tsuda Y, Ohashi K, Shimizu T, Okano T As proposed in the late 1980s by Langer and Vacanti, the ultimate goal of tissue engineering is the development of structures that can be used to treat or replace damaged or diseased organs and tissues. For the regeneration of various organs such as the heart, liver, and kidney, the development of adequate vascular networks within the engineered tissues remains a significant obstacle in the formation of cell-dense structures that resemble the native parenchyma. While tissue engineering using biodegradable scaffolds has been successful in the re-creation of tissues where extracellular matrix is abundant, we have developed cell-sheet-based tissue engineering for the construction of tissues using laminar assemblies of cells harvested from temperature-responsive culture dishes. Using cell sheet engineering, we present new strategies for the development of organ-like tissue structures containing well-organized vascular networks. PMID: 20882505 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Progress in the field of electrospinning for tissue engineering applications. Adv Mater. 2009 Sep 4;21(32-33):3343-51 Authors: Agarwal S, Wendorff JH, Greiner A Electrospinning is an extremely promising method for the preparation of tissue engineering (TE) scaffolds. This technique provides nonwovens resembling in their fibrillar structures those of the extracellular matrix (ECM), and offering large surface areas, ease of functionalization for various purposes, and controllable mechanical properties. The recent developments toward large-scale productions combined with the simplicity of the process render this technique very attractive. Progress concerning the use of electrospinning for TE applications has advanced impressively. Different groups have tackled the problem of electrospinning for TE applications from different angles. Nowadays, electrospinning of the majority of biodegradable and biocompatible polymers, either synthetic or natural, for TE applications is straightforward. Different issues, such as cell penetration, incorporation of growth and differentiating factors, toxicity of solvents used, productivity, functional gradient, etc. are main points of current considerations. The progress in the use of electrospinning for TE applications is highlighted in this article with focus on major problems encountered and on various solutions available until now. PMID: 20882501 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Scaffold design and manufacturing: from concept to clinic. Adv Mater. 2009 Sep 4;21(32-33):3330-42 Authors: Hollister SJ Since Robert Langer and colleagues pioneered the concept of reconstructing tissue using cells transplanted on synthetic polymer matrices in the early 1990s, research in the field of tissue engineering and regenerative medicine has exploded. This is especially true in the development of new materials and structures that serve as scaffolds for tissue reconstruction. The basic tenet of the last two decades holds scaffolds as degradable materials providing temporary function while enhancing tissue regeneration through the delivery of biologics. Although a number of new scaffolding materials and structures have been developed in research laboratories, the application of such materials practice even has been extremely limited. This paper argues that better integration of all these factors is needed to bring scaffolds from "concept to clinic". It reviews current work in all these areas and suggests where future work and funding is needed. PMID: 20882500 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Hydrogels in regenerative medicine. Adv Mater. 2009 Sep 4;21(32-33):3307-29 Authors: Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field. PMID: 20882499 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Controlled growth factor delivery for tissue engineering. Adv Mater. 2009 Sep 4;21(32-33):3269-85 Authors: Tayalia P, Mooney DJ Growth factors play a crucial role in information transfer between cells and their microenvironment in tissue engineering and regeneration. They initiate their action by binding to specific receptors on the surface of target cells and the chemical identity, concentration, duration, and context of these growth factors contain information that dictates cell fate. Hence, the importance of exogenous delivery of these molecules in tissue engineering is unsurprising, considering their importance for tissue regeneration. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and their potential toxicity at high systemic levels, suggest that conventional routes of administration are unlikely to be effective. In this review, we provide an overview of the design criteria for growth factor delivery vehicles with respect to the growth factor itself and the microenvironment for delivery. We discuss various methodologies that could be adopted to achieve this localized delivery, and strategies using polymers as delivery vehicles in particular. PMID: 20882497 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Perspectives and challenges in tissue engineering and regenerative medicine. Adv Mater. 2009 Sep 4;21(32-33):3235-6 Authors: Langer R PMID: 20882493 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Coils Coated With the Cyclic Peptide SEK-1005 Accelerate Intra-aneurysmal Organization. Neurosurgery. 2010 Oct;67(4):984-92 Authors: Sano H, Toda M, Sugihara T, Uchiyama N, Hamada J, Iwata H BACKGROUND:: Although the treatment of intracranial aneurysms with detachable coils is now widely accepted, the problem of coil compaction and recanalization remains to be solved. OBJECTIVE:: To prevent recanalization by inducing intra-aneurysmal organization through prepared platinum coils coated with a novel cyclic peptide, SEK-1005, which can accelerate wound healing. METHODS:: Using a rat aneurysm model, we examined the tissue response to these coils. An SEK-1005-coated coil (SC) or unmodified coil was inserted into the ligated external carotid artery (ECA) sac of rats. The sacs were removed on day 14 or 42 after coil insertion and subjected to conventional and immunohistochemical examination. We evaluated the tissue response in the ECA sacs and compared the percentage of organized areas in the ECA sacs of rats with SCs and unmodified coils. RESULTS:: In SC rats, tissue organization was accelerated and the proliferation of α-smooth muscle actin- and vimentin-positive cells was promoted. On days 14 and 42, tissue organization was significantly greater in the ECA sacs of rats with SCs. CONCLUSION:: SCs accelerated intra-aneurysmal organization in our rat aneurysm model suggesting that platinum coils coated with the novel cyclic peptide SEK-1005 may prevent recanalization and improve the clinical outcome in patients treated by coil embolization. PMID: 20881563 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Special issue featuring articles from the International Symposium on Surface and Interface of Biomaterials (ISSIB-II). Biomed Mater. 2010 Oct;5(5):050201 Authors: Wang M The series of International Symposia on Surface and Interface of Biomaterials was conceived in 2005 and the first conference in this series (SIB2007) was successfully held in Chengdu, People's Republic of China, in October 2007. At SIB2007, after competitive bidding, Hong Kong was chosen to be the venue for the Second International Symposium on Surface and Interface of Biomaterials (ISSIB-II) and I took up the role of Chairman and hence the task of organizing the conference which ultimately took place in Hong Kong on 4-6 January 2010. ISSIB-II received nearly 200 abstracts (not including plenary and keynote lectures) from 17 countries around the world, and more than 150 registered delegates attended. After review, 166 papers were accepted by the ISSIB-II scientific committee. The papers presented at ISSIB-II covered the following areas: biomedical polymers and their surface modification, bioceramics, metallic biomaterials, biomedical composites, dental materials, nanoparticles and quantum dots in medicine, biosensors, materials and systems for the delivery of therapeutic agents, tissue engineering scaffolds and their applications, electrospinning of fibrous structures for medical applications, surface patterning and micro- and nano-fabrication, surface modification of Ti and Ti-based alloys, materials and their surface modification for blood-contacting medical devices, biomolecules and cells at the surface or interface and analysis of biomaterial surface and interface. The symposium aimed to provide an international forum for scientists, engineers, clinicians and medical device manufacturers to present and discuss the latest scientific findings and technological developments in areas concerning surface and interface of biomaterials. And it succeeded in achieving this goal. The Croucher Foundation, Hong Kong, and the Department of Mechanical Engineering of The University of Hong Kong generously provided sponsorship. In 2009, the Editors-in-Chief of Biomedical Materials, Professors F-Z Cui, I-S Lee and M Spector, kindly agreed to publish a special issue in the journal, featuring papers originating from ISSIB-II. All the articles submitted for this issue went through the normal peer-review process and only those that attained the high standards of publication of the journal were accepted. The papers in this special issue capture some of the most popular topics presented at ISSIB-II: the synthesis, characterization, testing, modeling, assessment, application, and other pertinent aspects of the surface and interface of biomaterials. In the first paper of this issue, Saito et al (2010) report their work in preparing the surface of a phospholipid polymer with phenylboronic acid moiety (PMBV) to utilize a specific biomolecule-based interaction with cells. They demonstrate that fibronectin has a high affinity to the PMBV surface and that the surface significantly accelerates the differentiation of mesenchymal stem cells (C3H10T1/2), which they hope will be useful in cell and tissue engineering. Kaklamani et al (2010) conducted surface modification of UHMWPE using active screen plasma nitriding (ASPN) and investigated the biocompatibility. ASPN has the advantage of providing homogeneous treatment of any shape or surface at low temperature and the authors show that ASPN treatment also has a positive effect on the adhesion and proliferation of 3T3 fibroblasts. Using their organic acid derived sol-gel bioactive glasses, Lei et al (2010) demonstrate through their paper that the surface morphology, structure and apatite-forming ability of and cellular response to bioactive glass particles can be controlled by changing the acid species. The paper by Hertl et al (2010) reports their investigation into a two-step heat treatment for oxygen diffusion hardening which can produce hard surfaces with a transition zone between the surface oxide layer and the ductile Ti substrate. Through their paper, Dong et al (2010) show that an antibacterial surface created by the active screen plasma alloying technology on stainless steel can achieve an effective reduction of Escherichia coli within 3 hours. For particle or short-fiber reinforced polymer dental composites, with the support of their experiments, Zhang and Zhang (2010) point out in their paper that mechanical performance is affected by the bonding between the filler and the matrix and also the dispersion of the filler. For a new Ti-Zr-Nb-Sn alloy developed for dental applications, Hu et al (2010) find that its in vitro wear performance is better than Ti and that it does not cause mucous membrane irritation. In another investigation into surface modified Ti conducted by Joska et al (2010), it is shown that a TiN coating provides better corrosion resistance than a ZrN coating in the presence of fluoride ions. A paper by Xie et al (2010) deals with the {\it in vitro} degradation behaviour of icaritin-containing TCP/PLGA composite scaffolds which may be used for bone tissue engineering. There are three papers on electrospinning in this issue. The first, by Tong and Wang (2010), compares negative voltage electrospinning with positive voltage electrospinning using a PHBV copolymer in the experiments. Negative voltage electrospinning is rarely investigated for constructing tissue engineering scaffolds but may be very useful for solving technical problems and forming unique scaffolds. The second paper is by the same group, Tong et al (2010), and reports their work on the electrospinning of carbonated hydroxyapatite/PHBV nanocomposite fibers and {\it in vitro} biological evaluation of the fibrous scaffolds, showing that electrospun composite scaffolds have potential for bone tissue engineering. The third paper in this group is by Wang et al (2010b), who demonstrate that, using NIH 3T3 cells, RGD modification significantly improves cellular biocompatibility of chitosan nanofibers but the orientation of nanofibers has little effect on cell proliferation. The next three papers focus on the topic of `surface modification of Ti and Ti-based alloys'. They deal with liquid precursor plasma spraying to form nanostructured hydroxyapatite coatings (Huang et al 2010a), the effect of magnesium incorporation in fluoridated hydroxyapatite coatings on osteoblastic cell response (Cai et al 2010), and bioactivity of Ti surfaces ablated by femtosecond laser (Wang et al 2010a). For blood-contacting medical devices, the paper by Huang et al (2010b) reports their work on ZnO films fabricated by radio frequency sputtering, showing that the surface with lower surface energy exhibits less plasma protein adsorption. In the last paper of this collection, Hsiao et al (2010) present their method to quantify cell--substrate interaction using an atomic force microscope and reveal that there is a high adhesive force for osteoblasts on chitosan. As the Guest Editor of this special issue of Biomedical Materials, I thank all the authors for preparing and submitting their manuscripts for inclusion. I would also like to express sincere gratitude to all the reviewers. I am very grateful to Dr A Messaritaki, Publisher of Biomedical Materials at IOP Publishing, for her timely advice, generous help and great support. The assistance provided by all the staff of the journal is also greatly appreciated. The Third International Symposium on Surface and Interface of Biomaterials will be held in Sapporo, Hokkaido, Japan, in the summer of 2011. I hope that this third meeting will be another successful conference on biomaterials and tissue engineering for the international research community. References Cai Y L, Zhang J J, Zhang S, Venkatraman S S, Zeng X T, Du H J and Mondal D 2010 Osteoblastic cell response on fluoridated hydroxyapatite coatings: the effect of magnesium incorporation Biomed. Mater. 5 054114 Dong Y, Li X, Bell T, Sammons R and Dong H 2010 Surface microstructure and antibacterial property of an active-screen plasma alloyed austenitic stainless steel surface with Cu and N Biomed. Mater. 5 054105 Hertl C, Werner E, Thull R and Gbureck U 2010 Oxygen diffusion hardening of cp-titanium for biomedical applications Biomed. Mater. 5 054104 Hsiao S-W, Thien D V H, Ho M-H, Hsieh H-J, Li C-H, Hung C-H and Li H-H 2010 Interactions between chitosan and cells measured by AFM Biomed. Mater. 5 054117 Hu X, Wei Q, Li C-Y, Deng J-Y, Liu S and Zhang L-Y 2010 Study of the surface wear resistance and biological properties of the Ti--Zr--Nb--Sn alloy for dental restoration Biomed. Mater. 5 054107 Huang Y, Song L, Huang T, Liu X, Xiao Y, Wu Y, Wu F and Gu Z 2010a Characterization and formation mechanism of nano-structured hydroxyapatite coatings deposited by the liquid precursor plasma spraying process Biomed. Mater. 5 054113 Huang Z-Y, Chen M, Pan S-R and Chen D-H 2010b Effect of surface microstructure and wettability on plasma protein adsorption to ZnO thin films prepared at different RF powers Biomed. Mater. 5 054116 Joska L, Fojt J, Hradilova M, Hnilica F and Cvrcek L 2010 Corrosion behaviour of TiN and ZrN in the environment containing fluoride ions Biomed. Mater. 5 054108 Kaklamani G, Mehrban N, Chen J, Bowen J, Dong H, Grover L and Stamboulis A 2010 Effect of plasma surface modification on the biocompatibility of UHMWPE Biomed. Mater. 5 054102 Lei B, Chen X, Wang Y, Zhao N, Du C and Fang L 2010 Fabrication, structure and biological properties of organic acid-derived sol--gel bioactive glasses Biomed. Mater. 5 054103 Saito A, Konno T, Ikake H, Kurita K and Ishihara K 2010 Control of cell function on a phospholipid polymer having phenylboronic acid moiety Biomed. Mater. 5 054101 Tong H-W and Wang M 2010 Electrospinning of fibrous polymer scaffolds using positive voltage or negative voltage: a comparative study Biomed. Mater. (ABSTRACT TRUNCATED) PMID: 20881323 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Tumorigenicity of pluripotent stem cells: biological insights from molecular imaging. J R Soc Interface. 2010 Sep 29; Authors: Kooreman NG, Wu JC Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the ability (i) to duplicate indefinitely while maintaining pluripotency and (ii) to differentiate into cell types of all three embryonic germ layers. These two properties of ESCs and iPSCs make them potentially suitable for tissue engineering and cell replacement therapy for many different diseases, including Parkinson's disease, diabetes and heart disease. However, one critical obstacle in the clinical application of ESCs or iPSCs is the risk of teratoma formation. The emerging field of molecular imaging is allowing researchers to track transplanted ESCs or iPSCs in vivo, enabling early detection of teratomas. PMID: 20880852 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Optimization and scale-up of Wharton's jelly-derived mesenchymal stem cells for clinical applications. Stem Cell Res. 2010 Sep 27; Authors: Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S, Ta M MSCs are promising candidates for stem cell therapy and regenerative medicine. Umbilical cord is the easiest obtainable biological source of MSCs and the Wharton's jelly of the umbilical cord is a rich source of fetus-derived stem cells. However, the use of MSCs for therapeutic application is based on their subsequent large-scale in vitro expansion. A fast and efficient protocol for generation of large quantities of MSCs is required to meet the clinical demand and biomedical research needs. Here we have optimized conditions for scaling up of WJ-MSCs. Low seeding density along with basic fibroblast growth factor (bFGF) supplementation in the growth medium, which is DMEM-KO, resulted in propagation of more than 1x10(8) cells within a time period of 15days from a single umbilical cord. The upscaled WJ-MSCs retained their differentiation potential and immunosuppressive capacity. They expressed the typical hMSC surface antigens and the addition of bFGF in the culture medium did not affect the expression levels of HLA-DR and CD 44. A normal karyotype was confirmed in the large-scale expanded WJ-MSCs. Hence, in this study we attempted rapid clinical-scale expansion of WJ-MSCs which would allow these fetus-derived stem cells to be used for various allogeneic cell-based transplantations and tissue engineering. PMID: 20880767 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The response of annulus fibrosus cell to fibronectin-coated nanofibrous polyurethane-anionic dihydroxyoligomer scaffolds. Biomaterials. 2010 Sep 27; Authors: Attia M, Santerre JP, Kandel RA Tissue engineering of the annulus fibrosus(AF), a component of the intervertebral disc, has proven to be challenging due to its complex oriented lamellar structure. Previously it was demonstrated that polyurethane (PU) scaffolds containing an anionic dihydroxy oligomers (ADO) may be suitable to use in this application. The current study examines whether matrix protein(s) coatings (collagen type I, collagen type I and fibronectin, fibronectin, or vitronectin) would promote cell and collagen orientation that more closely mimics native AF. The greatest cell attachment occurred when scaffolds were pre-coated with Fn. Cells on Fn-coated scaffolds were aligned parallel to scaffold fibers, a process that involved α5β1 integrin, as determined by integrin-specific blocking antibodies, which in turn reduced AF cell spreading and alignment. Cell shape was regulated by the actin cytoskeleton as cells grown in the presence of cytochalasin D did not spread. Cells on Fn-coated PU scaffolds formed fibrillar Fn, synthesized significantly more collagen, and showed linear alignment of the secreted type I collagen when compared to cells grown on the other protein-coated scaffolds and the non-coated control. Thus Fn-coating of PU-ADO scaffolds appears to promote properly oriented AF cells and collagen, which should facilitate developing AF tissue that more closely mimics the native tissue. PMID: 20880584 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Towards a quantitative understanding of oxygen tension and cell density evolution in fibrin hydrogels. Biomaterials. 2010 Sep 27; Authors: Demol J, Lambrechts D, Geris L, Schrooten J, Van Oosterwyck H The in vitro culture of hydrogel-based constructs above a critical size is accompanied by problems of unequal cell distribution when diffusion is the primary mode of oxygen transfer. In this study, an experimentally-informed mathematical model was developed to relate cell proliferation and death inside fibrin hydrogels to the local oxygen tension in a quantitative manner. The predictive capacity of the resulting model was tested by comparing its outcomes to the density, distribution and viability of human periosteum derived cells (hPDCs) that were cultured inside fibrin hydrogels in vitro. The model was able to reproduce important experimental findings, such as the formation of a multilayered cell sheet at the hydrogel periphery and the occurrence of a cell density gradient throughout the hydrogel. In addition, the model demonstrated that cell culture in fibrin hydrogels can lead to complete anoxia in the centre of the hydrogel for realistic values of oxygen diffusion and consumption. A sensitivity analysis also identified these two parameters, together with the proliferation parameters of the encapsulated cells, as the governing parameters for the occurrence of anoxia. In conclusion, this study indicates that mathematical models can help to better understand oxygen transport limitations and its influence on cell behaviour during the in vitro culture of cell-seeded hydrogels. PMID: 20880579 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human endothelial cell growth on mussel-inspired nanofiber scaffold for vascular tissue engineering. Biomaterials. 2010 Sep 27; Authors: Ku SH, Park CB The endothelialization of prosthetic scaffolds is considered to be an effective strategy to improve the effectiveness of small-diameter vascular grafts. We report the development of a nanofibrous scaffold that has a polymeric core and a shell mimicking mussel adhesive for enhanced attachment, proliferation, and phenotypic maintenance of human endothelial cells. Polycaprolactone (PCL) was chosen as a core material because of its good biodegradability and mechanical properties suitable for tissue engineering. PCL was electrospun into nanofibers with a diameter of approximately 700 nm and then coated with poly(dopamine) (PDA) to functionalize the surface of PCL nanofibers with numerous catechol moieties similar to mussel adhesives in nature. The formation of a PDA ad-layer was analyzed using multiple techniques, including scanning electron microscopy, Raman spectroscopy, and water contact angle measurements. When PDA-coated PCL nanofibers were compared to unmodified and gelatin-coated nanofibers, human umbilical vein endothelial cells (HUVECs) exhibited highly enhanced adhesion and viability, increased stress fiber formation, and positive expression of endothelial cell markers (e.g., PECAM-1 and vWF). PMID: 20880578 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Homologous structure-function relationships between native fibrocartilage and tissue engineered from MSC-seeded nanofibrous scaffolds. Biomaterials. 2010 Sep 27; Authors: Nerurkar NL, Han W, Mauck RL, Elliott DM Understanding the interplay of composition, organization and mechanical function in load-bearing tissues is a prerequisite in the successful engineering of replacement tissues to replace diseased ones. Mesenchymal stem cells (MSCs) seeded on electrospun scaffolds have been successfully used to generate organized tissues that mimic fibrocartilages such as the knee meniscus and the annulus fibrosus of the intervertebral disc. While matrix deposition has been observed in parallel with improved mechanical properties, how composition, organization, and mechanical function are related is not known. Moreover, how this relationship compares to that of native fibrocartilage is unclear. Therefore, in the present work, functional fibrocartilage constructs were formed from MSC-seeded nanofibrous scaffolds, and the roles of collagen and glycosaminoglycan (GAG) in compressive and tensile properties were determined. MSCs deposited abundant collagen and GAG over 120 days of culture, and these extracellular molecules were organized in such a way that they performed similar mechanical functions to their native roles: collagen dominated the tensile response while GAG was important for compressive properties. GAG removal resulted in significant stiffening in tension. A similar stiffening response was observed when GAG was removed from native inner annulus fibrosus, suggesting an interaction between collagen fibers and their surrounding extrafibrillar matrix that is shared by both engineered and native fibrocartilages. These findings strongly support the use of electrospun scaffolds and MSCs for fibrocartilage tissue engineering, and provide insight on the structure-function relations of both engineered and native biomaterials. PMID: 20880577 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Endothelial Differentiation of Adipose-Derived Stem Cells from Elderly Patients with Cardiovascular Disease. Stem Cells Dev. 2010 Sep 29; Authors: Zhang P, Moudgill N, Hager E, Tarola N, Dimatteo C, McIlhenny S, Tulenko TN, Dimuzio P Adipose-derived stem cells (ASC) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASC isolated from elderly patients. Isolation of ASC from 53 patients (50-89 years) revealed that advanced age or co-morbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) compared to younger. ASC cultured in Endothelial Growth Medium-2 (EGM2) for up to three weeks formed cords upon Matrigel and demonstrated acLDL and lectin uptake. Further stimulation with VEGF and shear stress up-regulated EC-specific markers (CD31, von Willebrand factor, eNOS, and VE-cadherin). Inhibition of the PI3K but not MAPK pathway blocked the observed endothelial differentiation. Shear stress promoted an anti-thrombogenic phenotype as demonstrated by production of tissue-Plasminogen Activator (tPA) and nitric oxide, and inhibition of Plasminogen Activator Inhibitor-1. Shear stress augmented integrin α5β1 expression and subsequently increased attachment of differentiated ASC to basement membrane components. Finally, ASC seeded onto a decellularized vein graft resisted detachment despite application of shear force up to 9 dynes. These results suggest: 1) advanced age and co-morbidity do not negatively impact isolation of ASC, and 2) these stem cells retain significant capacity to acquire key endothelial cell traits throughout life. As such, adipose tissue is a practical source of autologous stem cells for vascular tissue engineering. PMID: 20879833 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineered heart tissue: a novel tool to study the ischemic changes of the heart in vitro. PLoS One. 2010;5(2):e9275 Authors: Katare RG, Ando M, Kakinuma Y, Sato T BACKGROUND: Understanding the basic mechanisms and prevention of any disease pattern lies mainly on development of a successful experimental model. Recently, engineered heart tissue (EHT) has been demonstrated to be a useful tool in experimental transplantation. Here, we demonstrate a novel function for the spontaneously contracting EHT as an experimental model in studying the acute ischemia-induced changes in vitro. METHODOLOGY/PRINCIPAL FINDINGS: EHT was constructed by mixing cardiomyocytes isolated from the neonatal rats and cultured in a ring-shaped scaffold for five days. This was followed by mechanical stretching of the EHT for another one week under incubation. Fully developed EHT was subjected to hypoxia with 1% O(2) for 6 hours after treating them with cell protective agents such as cyclosporine A (CsA) and acetylcholine (ACh). During culture, EHT started to show spontaneous contractions that became more synchronous following mechanical stretching. This was confirmed by the increased expression of gap junctional protein connexin 43 and improved action potential recordings using an optical mapping system after mechanical stretching. When subjected to hypoxia, EHT demonstrated conduction defects, dephosphorylation of connexin-43, and down-regulation of cell survival proteins identical to the adult heart. These effects were inhibited by treating the EHT with cell protective agents. CONCLUSIONS/SIGNIFICANCE: Under hypoxic conditions, the EHT responds similarly to the adult myocardium, thus making EHT a promising material for the study of cardiac functions in vitro. PMID: 20174664 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Engineered heart tissue: high throughput platform for dissection of complex diseases. J Cardiovasc Transl Res. 2008 Sep;1(3):232-5 Authors: Lazar J, Jacob HJ, Wakatsuki T The polygenic nature of resistance/sensitivity of the heart to ischemia is generally accepted. Unfortunately, little is known about gene(s) involved in response to this insult. The goal of present study is to introduce new tool, engineered heart tissue (EHT), for accelerating positional cloning and for providing novel functional assays. PMID: 20559925 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The elusive path to cartilage regeneration. Adv Mater. 2009 Sep 4;21(32-33):3419-24 Authors: Hunziker EB Numerous attempts have been made to develop an efficacious strategy for the repair of articular cartilage. These endeavors have been undaunted, if not spurred, by the challenge of the task and by the largely disappointing outcomes in animal models. Of the strategies that have been lately applied in a clinical setting, the autologous-chondrocyte-transplantation technique is the most notorious example. This methodology, which was prematurely launched on the clinical scene, was greeted with enthusiasm and has been widely adopted. However, a recent prospective and randomized clinical trial has revealed the approach to confer no advantage over conventional microfracturing. Why is the repair of articular cartilage such a seemingly intractable problem? The root of the evil undoubtedly lies in the tissue's poor intrinsic healing capacity. But the failure of investigators to tackle the biological stumbling blocks systematically rather than empirically is hardly a less inauspicious circumstance. Moreover, it is a common misbelief that the formation of hyaline cartilage per se suffices, whereas to be durable and functionally competent, the tissue must be fully mature. An appreciation of this necessity, coupled with a thorough understanding of the postnatal development of articular cartilage, would help to steer investigators clear of biological cul-de-sacs. PMID: 20882507 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Scaffold design and manufacturing: from concept to clinic. Adv Mater. 2009 Sep 4;21(32-33):3330-42 Authors: Hollister SJ Since Robert Langer and colleagues pioneered the concept of reconstructing tissue using cells transplanted on synthetic polymer matrices in the early 1990s, research in the field of tissue engineering and regenerative medicine has exploded. This is especially true in the development of new materials and structures that serve as scaffolds for tissue reconstruction. The basic tenet of the last two decades holds scaffolds as degradable materials providing temporary function while enhancing tissue regeneration through the delivery of biologics. Although a number of new scaffolding materials and structures have been developed in research laboratories, the application of such materials practice even has been extremely limited. This paper argues that better integration of all these factors is needed to bring scaffolds from "concept to clinic". It reviews current work in all these areas and suggests where future work and funding is needed. PMID: 20882500 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Endothelial Differentiation of Adipose-Derived Stem Cells from Elderly Patients with Cardiovascular Disease. Stem Cells Dev. 2010 Sep 29; Authors: Zhang P, Moudgill N, Hager E, Tarola N, Dimatteo C, McIlhenny S, Tulenko TN, Dimuzio P Adipose-derived stem cells (ASC) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASC isolated from elderly patients. Isolation of ASC from 53 patients (50-89 years) revealed that advanced age or co-morbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) compared to younger. ASC cultured in Endothelial Growth Medium-2 (EGM2) for up to three weeks formed cords upon Matrigel and demonstrated acLDL and lectin uptake. Further stimulation with VEGF and shear stress up-regulated EC-specific markers (CD31, von Willebrand factor, eNOS, and VE-cadherin). Inhibition of the PI3K but not MAPK pathway blocked the observed endothelial differentiation. Shear stress promoted an anti-thrombogenic phenotype as demonstrated by production of tissue-Plasminogen Activator (tPA) and nitric oxide, and inhibition of Plasminogen Activator Inhibitor-1. Shear stress augmented integrin α5β1 expression and subsequently increased attachment of differentiated ASC to basement membrane components. Finally, ASC seeded onto a decellularized vein graft resisted detachment despite application of shear force up to 9 dynes. These results suggest: 1) advanced age and co-morbidity do not negatively impact isolation of ASC, and 2) these stem cells retain significant capacity to acquire key endothelial cell traits throughout life. As such, adipose tissue is a practical source of autologous stem cells for vascular tissue engineering. PMID: 20879833 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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