| Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell-Cell Interactions : Sixth International Bio-Fluid Mechanics Symposium and Workshop March 28-30, 2008 Pasadena, California.
January 14, 2010 at 8:09 AM
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| | Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell-Cell Interactions : Sixth International Bio-Fluid Mechanics Symposium and Workshop March 28-30, 2008 Pasadena, California. Ann Biomed Eng. 2010 Jan 13; Authors: Chung S, Sudo R, Vickerman V, Zervantonakis IK, Kamm RD Recent advances in microfluidic technologies have opened the door for creating more realistic in vitro cell culture methods that replicate many aspects of the true in vivo microenvironment. These new designs (i) provide enormous flexibility in controlling the critical biochemical and biomechanical factors that influence cell behavior, (ii) allow for the introduction of multiple cell types in a single system, (iii) provide for the establishment of biochemical gradients in two- or three-dimensional geometries, and (iv) allow for high quality, time-lapse imaging. Here, some of the recent developments are reviewed, with a focus on studies from our own laboratory in three separate areas: angiogenesis, cell migration in the context of tumor cell-endothelial interactions, and liver tissue engineering. PMID: 20069368 [PubMed - as supplied by publisher] | | |
| Analysis of Collagen and Glucose Modulated Cell Growth within Tissue Engineered Scaffolds.
January 14, 2010 at 8:09 AM
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| | Analysis of Collagen and Glucose Modulated Cell Growth within Tissue Engineered Scaffolds. Ann Biomed Eng. 2010 Jan 13; Authors: Chung CA, Ho SY The strategy of tissue engineering includes seeding cells onto porous scaffolds. The cellular construct is cultured in vitro for a period of time before transplantation for the patient. Because of the intrinsic complexity of biological systems, it is valuable to have models of simulation that can assess the culture conditions and optimize experiments. This work presents a mathematical model to account for the effects of glucose and type II collagen on chondrocyte growth under static culture conditions. Dependence of cell growth on collagen was assumed as a biphasic function of collagen quantity, whereby the cell growth rate increases and then decreases with increasing collagen content. Results from simulation were compared with experimental data in literature. The model was then applied to investigate the effects of cell seeding area, demonstrating the spatiotemporal evolution of cell distribution in scaffolds. Results show that the conventional uniform seeding me! thod may not be a good way of gaining uniform and large cell number densities at the final stage of cultivation. A seeding mode that has cells reside initially in the middle area of scaffold was shown to be able to not only reduce the diffusion limitation of nutrients but also weaken the inhibiting impact of aggregated collagen on cell growth. Therefore the middle seeding mode may result in better cell amounts and uniformities for developing tissue engineered constructs. PMID: 20069364 [PubMed - as supplied by publisher] | | |
| Attenuation of TGFbeta Signaling Pathway in Chronic Venous Ulcers.
January 14, 2010 at 8:09 AM
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| | Attenuation of TGFbeta Signaling Pathway in Chronic Venous Ulcers. Mol Med. 2010 Jan 13; Authors: Pastar I, Stojadinovic O, Krzyzanowska A, Barrientos S, Stuelten C, Zimmerman K, Blumenberg M, Brem H, Tomic-Canic M TGFbeta is important in inflammation, angiogenesis, re-epithelialization and connective tissue regeneration during wound healing. We analyzed components of TGFbeta signaling pathway in biopsies from ten patients with non-healing venous ulcers (VUs). Using comparative genomics of transcriptional profiles of VUs and TGFbeta treated keratinocytes, we found deregulation of TGFbeta target genes in VUs. Using qPCR and immunohistochemistry, we found suppression of TGFbetaRI, RII and RIII and complete absence of phosphorylated Smad2 (pSmad2) in VUs epidermis. In contrast, pSmad2 was induced in the cells of migrating epithelial tongue of acute wounds. TGFbeta inducible transcription factors (GADD45beta, ATF3 and ZFP36L1) were suppressed in VUs. Likewise, genes suppressed by TGFbeta (FABP5, CSTA and S100A8) were induced in non-healing VUs. An inhibitor of Smad signaling, Smad7 was also down-regulated in VUs. We conclude that TGFbeta signaling is functionally blocked in VUs ! by down-regulation of TGFbeta receptors and attenuation of Smad signaling resulting in deregulation of TGFbeta target genes and consequent hyperproliferation. These data suggest that application of exogenous TGFbeta may not be beneficial treatment for VUs. PMID: 20069132 [PubMed - as supplied by publisher] | | |
| Return to Duty Rate of Amputee Soldiers in the Current Conflicts in Afghanistan and Iraq.
January 14, 2010 at 8:09 AM
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| | Return to Duty Rate of Amputee Soldiers in the Current Conflicts in Afghanistan and Iraq. J Trauma. 2010 Jan 9; Authors: Stinner DJ, Burns TC, Kirk KL, Ficke JR BACKGROUND:: The purpose of this study was to determine the percentage of amputee soldiers who sustained their injury during the current conflicts in Afghanistan and Iraq and have returned to duty. In addition, the authors plan to identify the factors that influence the amputee's likelihood to return to duty. METHODS:: The computerized records of amputee soldiers who presented to the Physical Evaluation Board between October 1, 2001 and June 1, 2006 were reviewed. This data were crossreferenced with the Military Amputee Database. The following variables were extracted: age, gender, pay grade, amputation level, and final disposition. RESULTS:: During the period reviewed, there were 395 major limb amputees that met inclusion criteria. Of those, 65 returned to active duty (16.5%). The average age of amputees returning to duty was more than 4 years older than those who separated from the service (31.4 vs. 27.2), p < 0.0001. Officers and senior enlisted personnel re! turned to duty at a higher rate (35.3% and 25.5%, respectively) when compared with junior enlisted personnel (7.0%), p < 0.0001. Those with multiple extremity amputations have the lowest return to duty rate at 3%, when compared with the overall return to duty rate for single extremity amputees (20%), p < 0.0001. CONCLUSION:: During the 1980s, 11 of 469 amputees returned to active duty (2.3%). The number of amputees returning to duty has increased significantly, from 2.3% to 16.5%, due to advancements in combat casualty care and the establishment of centralized amputee centers. PMID: 20068483 [PubMed - as supplied by publisher] | | |
| The Chemical Defensive System in the Pathobiology of Idiopathic Environment-Associated Diseases.
January 14, 2010 at 8:09 AM
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| | The Chemical Defensive System in the Pathobiology of Idiopathic Environment-Associated Diseases. Curr Drug Metab. 2010 Jan 7; Authors: Korkina L, Scordo G, Deeva I, Cesareo E, De Luca C Chemical defensive system consisting of bio-sensoring, transmitting, and responsive elements has been evolved to protect multi-cellular organisms against environmental chemical insults (xenobiotics) and to maintain homeostasis of endogenous low molecular weight metabolites (endobiotics). Both genetic and epigenetic defects of the system in association with carcinogenesis and individual sensitivity to anti-tumor therapies have been intensely studied. Recently, several non-tumor human pathologies with evident environmental components such as rather rare functional syndromes (multiple chemical sensitivity, chronic fatigue, Persian Gulf, and fibromyalgia now collectively labeled as idiopathic environmental intolerances) and common diseases (vitiligo and systemic lupus erythematosus) have become subjects of the research on the impaired metabolism and detoxification of xenobiotics and endogenous toxins. Here, we collected and critically reviewed epidemiological, genetic! , and biochemical data on the involvement and possible role of cytochrome P450 super family enzymes, glutathione-S-transferase isozymes, catechol-O-methyl-transferase, UDP-glucuronosyl transferases, and proteins detoxifying inorganic and organic peroxides (catalase, glutathione peroxidase, and peroxiredoxin) in the above pathologies. Genetic predisposition assessed mainly by single nucleotide polymorphism and gene expression analyses revealed correlations between defects in genes encoding xenobiotic-metabolizing and/or detoxifying enzymes and risk/severity of these syndromes/diseases. Proteome analysis identified abnormal expression of the enzymes. Their functions were affected epigenetically leading to metabolic impairment and, as a consequence, to the negative health outcomes shared by some of these pathologies. Data obtained so far suggest that distinct components of the chemical defensive system could be suitable molecular targets for future pathogenic therapies. PMID: 20067442 [PubMed - as supplied by publisher] | | |
| Improving chondrogenesis - potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering.
January 14, 2010 at 8:09 AM
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| | Improving chondrogenesis - potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering. Tissue Eng Part A. 2010 Jan 12; Authors: Kupcsik L, Stoddart MJ, Li Z, Benneker LM, Alini M Articular cartilage injuries and degeneration affect a large proportion of the population in developed countries world wide. Stem cells can be differentiated into chondrocytes by adding transforming growth factor beta1 (TGF beta1) and dexamethasone to a pellet culture, which are unfeasible for tissue engineering purposes. We attempted to achieve stable chondrogenesis without any requirement for exogenous growth factors. Human mesenchymal stem cells were transduced with an adenoviral vector containing SRY-related HMG-box gene 9 (SOX9), and were cultured in a 3D hydrogel scaffold composite. As an additional treatment mechanical stimulation was applied in a custom-made bioreactor. SOX9 increased the expression of its known target genes, as well as its co-factors: the long form of SOX5 and SOX6. However, it was unable to increase the synthesis of sulfated glycosaminoglycans (GAG). Mechanical stimulation slightly enhanced collagen type X and increased lubricin expressi! on. The combination of SOX9 and mechanical load boosted GAG synthesis as shown by 35S incorporation. GAG production rate corresponded well to the amount of (endogenous) TGF beta1. Finally, cartilage oligomeric matrix protein expression was increased by both treatments. These findings provide insight into the mechano-transduction of MSCs and demonstrate the potential of a transcription factor in stem cell therapy. PMID: 20067399 [PubMed - as supplied by publisher] | | |
| A feasibility of useful cell-based therapy by bone regeneration with deciduous tooth stem cells, dental pulp stem cells, or bone marrow-derived mesenchymal stem cells for clinical study using tissue engineering technology.
January 14, 2010 at 8:09 AM
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| | A feasibility of useful cell-based therapy by bone regeneration with deciduous tooth stem cells, dental pulp stem cells, or bone marrow-derived mesenchymal stem cells for clinical study using tissue engineering technology. Tissue Eng Part A. 2010 Jan 12; Authors: Yamada Y, Nakamura S, Ito K, Sugito T, Yoshimi R, Nagasaka T, Ueda M This study investigated the effect on bone regeneration with dental pulp stem cells (DPSCs), deciduous tooth stem cells (DTSCs), or bone marrow-derived mesenchymal stem cells (BMMSCs) for clinical study, in hydroxyapatite (HA)-coated osseointegrated dental implants, using tissue engineering technology. In vitro, human DPSCs and DTSCs expressed STRO-1, CD13, CD29, CD 44, CD73, and osteogenic marker genes such as alkaline phosphatase (ALP), RUNX 2, osteocalcin (OCN). In vivo, prepared bone defect model was implanted by graft materials as follows: PRP, PRP and canine BMMSCs (cBMMSCs), PRP and canine DPSCs (cDPSCs), PRP and puppy DTSCs (pDTSCs), and control (defect only). After 8 weeks, the dental implants were installed, and 16 weeks later the sections were evaluated histologically and histometrically. The cBMMSCs/PRP, cDPSCs/PRP, and pDTSCs/PRP groups had well-formed mature bone and neovascularization. Histometrically, the bone implant contact (BIC) was significant ! differences between the cBMMSCs/PRP, cDPSCs/PRP, pDTSCs/PRP groups, and the control and PRP groups (p<0.01). These results demonstrated that these stem cells with PRP have the ability to form bone, and this bone formation activity might be useful for osseointegrated HA-coated dental implants with good levels of BIC. PMID: 20067397 [PubMed - as supplied by publisher] | | |
| High-Throughput Discovery of Synthetic Surfaces That Support Proliferation of Pluripotent Cells.
January 14, 2010 at 8:09 AM
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| | High-Throughput Discovery of Synthetic Surfaces That Support Proliferation of Pluripotent Cells. J Am Chem Soc. 2010 Jan 12; Authors: Derda R, Musah S, Orner BP, Klim JR, Li L, Kiessling LL Synthetic materials that promote the growth or differentiation of cells have advanced the fields of tissue engineering and regenerative medicine. Most functional biomaterials are based on a handful of peptide sequences derived from protein ligands for cell surface receptors. Because few proteins possess short peptide sequences that alone can engage cell surface receptors, the repertoire of receptors that can be targeted with this approach is limited. Materials that bind diverse classes of receptors, however, may be needed to guide cell growth and differentiation. To provide access to such new materials, we utilized phage display to identify novel peptides that bind to the surface of pluripotent cells. Using human embryonal carcinoma (EC) cells as bait, approximately 3 x 10(4) potential cell-binding phage clones were isolated. The pool was narrowed using an enzyme-linked immunoassay: 370 clones were tested, and seven cell-binding peptides were identified. Of these,! six sequences possess EC cell-binding ability. Specifically, when displayed by self-assembled monolayers (SAMs) of alkanethiols on gold, they mediate cell adhesion. The corresponding soluble peptides block this adhesion, indicating that the identified peptide sequences are specific. They also are functional. Synthetic surfaces displaying phage-derived peptides support growth of undifferentiated human embryonic stem (ES) cells. When these cells were cultured on SAMs presenting the sequence TVKHRPDALHPQ or LTTAPKLPKVTR in a chemically defined medium (mTeSR), they expressed markers of pluripotency at levels similar to those of cells cultured on Matrigel. Our results indicate that this screening strategy is a productive avenue for the generation of materials that control the growth and differentiation of cells. PMID: 20067240 [PubMed - as supplied by publisher] | | |
| [Bone marrow mesenchymal stem cell therapy on diabetic nephropathy in rats]
January 14, 2010 at 8:09 AM
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| | [Bone marrow mesenchymal stem cell therapy on diabetic nephropathy in rats] Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Nov;40(6):1024-8 Authors: Zhou H, Gao Y, Tian HM OBJECTIVE: To test the effectiveness of bone marrow mesenchymal stem cell (MSC) transplantation on diabetic nephropathy in rats. METHODS: A single intraperitoneal injection of STZ (60 mg/kg) was given to Sprague-Dawley (SD) rats. Four weeks after the occurrence of diabetes, the rats with diabetic nephropathy were randomly divided into two groups: diabetic nephropathy control group (DN, n = 12) and MSCs transplantation group (MSC, n = 12). Six rats served as normal controls. MSCs were cultured, identified and labeled by 5-bromo-2'-deoxyuridine (BrdU) in vitro, which were then transplanted to the rats in the MSC group via introcardiac infusion(2 x 10(6) MSCs/200 microL). The same procedure was repeated one week later. The blood glucose, body weight (BW), kidney weight (KW), urine protein, endogenous creatinine clearance rate (Ccr) and profile of kidney hypertrophy (KW/BW) were tested and the renal morphology and labeled cells were examined in the kidney, one, two, a! nd eight weeks after the second transplantation. RESULTS: Mesenchymal cell phenotype was expressed by the cultured MSCs, which could be multidifferentiated into osteogenic and adipogenic cells. The labeled MSCs were detected in the kidney of nephropathic rats, but no proliferation of the stem cells was found. The rats in the MSC and DN groups had higher blood glucose, urine protein, Ccr and KW/BW and lower BW than the normal controls (P < 0.05). One week after the transplantation, the rats in the MSC group showed lower blood glucose than the rats in the DN group [(26.7 +/- 2.8) vs (29.9 +/- 1.6) mmol/L, P < 0.05], but was still higher than the normal controls (6.0 +/- 0.7 mmol/L). The urine protein appeared similar in the MSC and DN groups two weeks and eight weeks after transplantation. After two weeks of transplantation, the rats in the MSC group showed lower Ccr (8.6 +/- 1.9) and KW/BW (5.5 +/- 0.1) than the rats in the DN group (17.1 +/- 1.6 for Ccr and 6.2 +/- 0.! 3 for KW/BW respectively, P < 0.05). CONCLUSION: Cardiac in! jected b one marrow mesenchymal stem cells can track to the kidney of rats with diabetic nephropathy, which attenuates diabetic nephropathy temporarily. PMID: 20067112 [PubMed - in process] | | |
| Designing materials to direct stem-cell fate.
January 14, 2010 at 8:09 AM
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| | Designing materials to direct stem-cell fate. Nature. 2009 Nov 26;462(7272):433-41 Authors: Lutolf MP, Gilbert PM, Blau HM Proper tissue function and regeneration rely on robust spatial and temporal control of biophysical and biochemical microenvironmental cues through mechanisms that remain poorly understood. Biomaterials are rapidly being developed to display and deliver stem-cell-regulatory signals in a precise and near-physiological fashion, and serve as powerful artificial microenvironments in which to study and instruct stem-cell fate both in culture and in vivo. Further synergism of cell biological and biomaterials technologies promises to have a profound impact on stem-cell biology and provide insights that will advance stem-cell-based clinical approaches to tissue regeneration. PMID: 19940913 [PubMed - indexed for MEDLINE] | | |
| Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells.
January 14, 2010 at 8:09 AM
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| | Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells. Stem Cells. 2009 Aug;27(8):1869-78 Authors: Tran TH, Wang X, Browne C, Zhang Y, Schinke M, Izumo S, Burcin M In vitro differentiation of human embryonic stem cells (hESCs) into pure human cardiomyocytes (hESCMs) would present a powerful tool to further the creation of cell models designed to advance preclinical drug development. Here, we report a novel differentiation method to substantially increase hESCM yield. Upon early and transient treatment of hESCs with Wnt3a, embryoid body and mesendoderm formation is enhanced, leading to greater differentiation toward cardiomyocytes. Moreover, the generated beating clusters are highly enriched with cardiomyocytes (50%) and express genes characteristic of cardiac cells, providing evidence that these hESCMs are competent to develop in vitro into functional and physiologically relevant cardiomyocytes. In summary, this protocol not only has the potential to guarantee a renewable supply of enriched cardiomyocyte populations for developing novel and more predictive cell models, but it also should provide valuable insights into pathwa! ys critical for cardiac regeneration. PMID: 19544447 [PubMed - indexed for MEDLINE] | | |
| The effect of implantation on scaffoldless three-dimensional engineered bone constructs.
January 14, 2010 at 8:09 AM
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| | The effect of implantation on scaffoldless three-dimensional engineered bone constructs. In Vitro Cell Dev Biol Anim. 2009 Oct;45(9):512-22 Authors: Smietana MJ, Syed-Picard FN, Ma J, Kostrominova T, Arruda EM, Larkin LM Our laboratory has previously developed scaffoldless engineered bone constructs (EBC). Bone marrow stromal cells (BMSC) were harvested from rat femur and cultured in medium that induced osteogenic differentiation. After reaching confluence, the monolayer of cells contracted around two constraint points forming a cylinder. EBCs were placed in small diameter (0.5905 x 0.0625 in.) or large diameter (0.5905 x 0.125 in.) silicone tubing and implanted intramuscularly in the hind limb of a rat. Bone mineral content (BMC) of the EBC was analyzed before implantation and at 1 and 2 mo following implantation and compared to that of native femur bone at different stages of development. Negligible BMC was observed in E-20 femur or EBCs prior to implantation. One-month implantation in both small and large tubing increased BMC in the EBC. BMC of EBC from large tubing was greater than in 14 d rat neonatal femurs, but was 2% and 3% of BMC content in adult bone after 1 and 2 mo of ! implantation, respectively. Alizarine Red and osteopontin staining of the EBCs before and after implantation confirmed increased bone mineralization in the implanted EBCs. Implanted EBCs also had extensive vascularization. Our data suggest that BMSC can be successfully used for the generation of scaffoldless EBC, and this model can be potentially used for the generation of autologous bone transplants in humans. PMID: 19533254 [PubMed - indexed for MEDLINE] | | | |
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