| Clemson University researcher regenerates brain tissue in traumatic injuries
September 2, 2009 at 6:07 pm
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| Study results promise faster recovery from life-threatening blood cell shortages
September 2, 2009 at 4:07 pm
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| Canadian research breakthrough holds promise for development of effective cancer therapies
September 2, 2009 at 2:07 pm
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| BioTime CEO Dr. Michael West to Present at 2009 World Stem Cell Summit
September 2, 2009 at 10:06 am
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| The effects of BMP6 overexpression on adipose stem cell chondrogenesis: Interactions with dexamethasone and exogenous growth factors.
September 2, 2009 at 6:52 am
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| | The effects of BMP6 overexpression on adipose stem cell chondrogenesis: Interactions with dexamethasone and exogenous growth factors. J Biomed Mater Res A. 2009 Aug 31; Authors: Diekman BO, Estes BT, Guilak F Adipose-derived stem cells (ASCs) are multipotent progenitors that can be chondrogenically induced by growth factors such as bone morphogenetic protein 6 (BMP-6). We hypothesized that nonviral transfection of a BMP-6 construct (pcDNA3-BMP6) would induce chondrogenic differentiation of ASCs encapsulated in alginate beads and that differentiation would be enhanced by the presence of the synthetic glucocorticoid dexamethasone (DEX) or the combination of epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), and transforming growth factor beta-1 (TGF-beta1), collectively termed expansion factors (EFs). Chondrogenesis was assessed using quantitative real-time polymerase chain reaction for types I, II, and X collagen, aggrecan, and BMP6. Immunohistochemistry was performed with antibodies for types I, II, and X collagen and chondroitin-4-sulfate. BMP6 overexpression alone induced a moderate chondrogenic response. The inclusion of EFs promoted robust type II collagen expression but also increased type I and X collagen deposition, consistent with a hypertrophic chondrocyte phenotype. Early gene expression data indicated that DEX was synergistic with BMP-6 for chondrogenesis, but immunohistochemistry at 28 days showed that DEX reduced glycosaminoglycan accumulation. These results suggest that chondrogenic differentiation of ASCs depends on complex interactions among various growth factors and media supplements, as well as the concentration and duration of growth factor exposure. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009. PMID: 19722282 [PubMed - as supplied by publisher] |
| Electrospun scaffolds from silk fibroin and their cellular compatibility.
September 2, 2009 at 6:44 am
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| | Electrospun scaffolds from silk fibroin and their cellular compatibility. J Biomed Mater Res A. 2009 Aug 31; Authors: Zhang K, Mo X, Huang C, He C, Wang H Electrospinning offers an attractive opportunity for producing silk fibroin (SF) nano/micro fibrous scaffolds with potential for tissue regeneration and repair. Electrospun scaffolds of silk fibroin were fabricated as a biomimetic scaffold for tissue engineering. The morphology of the electrospun scaffolds was investigated with SEM and AFM. The SEM images indicated that electrospun SF fibers were ribbon-shaped and the average width increased with increasing SF concentrations. The AFM images revealed that, after treated with methanol, there was a groove on the surface of fiber, which is conducive to cell attachment. The structure of electrospun SF fibers was characterized by NMR, WAXD, and DSC. The results displayed that SF in electrospun fibers was present in a random coil conformation, SF conformation transformed from random coil to beta-sheet when treated with methanol. Cell attachment and proliferation studies with pig iliac endothelial cells (PIECs) demonstrated that electrospun SF scaffolds significantly promoted cell attachment and proliferation in comparison with cast SF films. These results suggest electrospun SF scaffolds may be potential candidates for cardiovascular tissue engineering. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009. PMID: 19722283 [PubMed - as supplied by publisher] |
| Fabrication of silk fibroin blended P(LLA-CL) nanofibrous scaffolds for tissue engineering.
September 2, 2009 at 6:44 am
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| | Fabrication of silk fibroin blended P(LLA-CL) nanofibrous scaffolds for tissue engineering. J Biomed Mater Res A. 2009 Aug 31; Authors: Zhang K, Wang H, Huang C, Su Y, Mo X, Ikada Y Electrospinning using natural proteins and synthetic polymers offers an attractive technique for producing fibrous scaffolds with potential for tissue regeneration and repair. Nanofibrous scaffolds of silk fibroin (SF) and poly(L-lactic acid-co-epsilon-caprolactone) (P(LLA-CL)) blends were fabricated using 1,1,1,3,3,3-hexafluoro-2-propanol as a solvent via electrospinning. The average nanofibrous diameter increased with increasing polymer concentration and decreasing the blend ratio of SF to P(LLA-CL). Characterizations of XPS and (13)C NMR clarified the presence of SF on their surfaces and no obvious chemical bond reaction between SF with P(LLA-CL) and SF in SF/P(LLA-CL) nanofibers was present in a random coil conformation, SF conformation transformed from random coil to beta-sheet when treated with water vapor. Whereas water contact angle measurements conformed greater hydrophilicity than P(LLA-CL). Both the tensile strength and elongation at break increased with the content increasing of P(LLA-CL). Cell viability studies with pig iliac endothelial cells demonstrated that SF/P(LLA-CL) blended nanofibrous scaffolds significantly promoted cell growth in comparison with P(LLA-CL), especially when the weight ratio of SF to P(LLA-CL) was 25:75. These results suggested that SF/P(LLA-CL) blended nanofibrous scaffolds might be potential candidates for vascular tissue engineering. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009. PMID: 19722280 [PubMed - as supplied by publisher] |
| Effects of growth factors on equine synovial fibroblasts seeded on synthetic scaffolds for avascular meniscal tissue engineering.
September 2, 2009 at 6:44 am
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| | Effects of growth factors on equine synovial fibroblasts seeded on synthetic scaffolds for avascular meniscal tissue engineering. Res Vet Sci. 2009 Aug 29; Authors: Fox DB, Warnock JJ, Stoker AM, Luther JK, Cockrell M Across species, the avascular portion of the knee meniscus cannot heal spontaneously if severely injured. The most common treatment is meniscectomy which results in osteoarthritis. The objective of this study was to assess the fibrochondrogenic potential of equine fibroblast-like synoviocytes (FLS) seeded on scaffolds under the influence of growth factors in vitro to determine the potential of developing a novel cell-based repair strategy. Cultured FLS were seeded onto synthetic scaffolds in a rotating bioreactor under the influence of three growth factor regimens: none, basic fibroblast growth factor (bFGF) alone, and bFGF plus transforming growth factor (TGF-beta(1)) and insulin-like growth factor (IGF-1). Constructs were analyzed for mRNA expression and production of fibrochondroid extracellular matrix constituents. Type II collagen and aggrecan mRNA were significantly higher in growth factor-treated groups (p<0.05). Despite sub-optimal extracellular matrix production, FLS can exhibit fibrochondral characteristics and may have potential for cell-based tissue engineering for avascular meniscal regeneration. PMID: 19720387 [PubMed - as supplied by publisher] |
| Isolation of cancer specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter.
September 2, 2009 at 6:44 am
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| | Isolation of cancer specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter. Genomics. 2009 Aug 28; Authors: Cruickshanks HA, Tufarelli C The antisense promoter of human LINE-1 (L1) retroelements can direct transcription of adjacent unique genomic sequences generating chimeric RNAs, which can perturb transcription of neighbouring genes. As L1 elements constitute 17% of the human genome, chimeric transcription is potentially widespread, but the extent to which this occurs is largely unknown. Using a genome-wide screen we have isolated novel chimeric transcripts that are unique to breast cancer cell lines, primary tumours and colon cancer cells. Expression of the cancer specific chimeric transcripts can be induced in non-malignant breast epithelial cells by the demethylating drug 5-azacytidine. These findings indicate that loss of L1 methylation in cancer cells is linked to expression of L1-chimeric transcripts which may therefore constitute a useful set of markers of malignancy. PMID: 19720139 [PubMed - as supplied by publisher] |
| Factors influencing the oxygen consumption rate of aortic valve interstitial cells: application to tissue engineering.
September 2, 2009 at 6:44 am
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| | Factors influencing the oxygen consumption rate of aortic valve interstitial cells: application to tissue engineering. Tissue Eng Part C Methods. 2009 Sep;15(3):355-63 Authors: Wang L, Wilshaw SP, Korossis S, Fisher J, Jin Z, Ingham E This study investigated the factors influencing the oxygen metabolism of aortic valve interstitial cells (VICs). Porcine VICs in cell suspension at different passages, and adhered to coverslips at different confluencies, as well as fresh porcine valve leaflets, were incubated in an oxygen respiration chamber at 37 degrees C in Dulbecco's modified Eagle's medium. The consumption rates at different oxygen concentrations were evaluated based on the Michaelis-Menten equation, and the corresponding maximum consumption rate (V(max)) and the Michaelis-Menten equation constant K(m) were determined. In all cases, the oxygen consumption rate was relatively constant until the concentration dropped to 5% (v/v). The metabolic activity of VICs in terms of oxygen consumption was dependent upon their in vitro passage number and proliferation status. These findings will provide valuable input to the selection of VICs with respect to their age and proliferation status for tissue engineering applications, as well as important input parameters for developing computational models of oxygen transport and optimization of the bioreactor conditions for heart valve tissue engineering. PMID: 19719392 [PubMed - in process] |
| Effect of platelet-rich plasma and latissimus dorsi muscle flap on osteogenesis and vascularization of tissue-engineered bone in dogs.
September 2, 2009 at 6:44 am
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| | Effect of platelet-rich plasma and latissimus dorsi muscle flap on osteogenesis and vascularization of tissue-engineered bone in dogs. J Oral Maxillofac Surg. 2009 Sep;67(9):1850-8 Authors: Li NY, Yuan RT, Chen T, Chen LQ, Jin XM PURPOSE: The present study evaluated the effects of platelet-rich plasma (PRP) and the latissimus dorsi muscle flap on osteogenesis and vascularization of tissue-engineered bone. MATERIALS AND METHODS: Bone marrow stromal cells (BMSCs) were subcultured, and PRP was obtained from the same dogs. Demineralized bone matrix (DBM) was prepared from homologous bone. The complexes of DBM/BMSCs/PRP were implanted into areas A and B on the left side of the dogs' backs; complexes of DBM/BMSCs without PRP were implanted in areas C and D on the right side of the same dog. The implants in areas A and C were wrapped with a latissimus dorsi muscle flap, and the implants in areas B and D were wrapped with inferior fascia. At 4, 8, and 12 weeks later, the implants were removed for evaluation. RESULTS: The radiographic evaluation, descriptive histologic analysis, and histologic quantitative analysis showed that the PRP/BMSCs/DBM complex was better than the BMSCs/DBM complex in both vascularization and osteogenesis of the ectopic tissue-engineered bones, and the complex wrapped with the latissimus dorsi muscle flap was better than that packed with superficial fascia without blood vessels. CONCLUSIONS: The PRP and blood vessels in the latissimus dorsi muscle could cooperatively promote osteogenesis and vascularization in tissue-engineered bone. PMID: 19686921 [PubMed - indexed for MEDLINE] |
| Control of the skin scarring response.
September 2, 2009 at 6:29 am
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| | Control of the skin scarring response. An Acad Bras Cienc. 2009 Sep;81(3):623-9 Authors: Ferreira LM, Gragnani A, Furtado F, Hochman B There comes a time when the understanding of the cutaneous healing process becomes essential due to the need for a precocious tissue repair to reduce the physical, social, and psychological morbidity. Advances in the knowledge on the control of interaction among cells, matrix and growth factors will provide more information on the Regenerative Medicine, an emerging area of research in medical bioengineering. However, considering the dynamism and complexity of the cutaneous healing response, it is fundamental to understand the control mechanism exerted by the interaction and synergism of both systems, cutaneous nervous and central nervous, via hypothalamus hypophysis-adrenal axis, a relevant subject, but hardly ever explored. The present study reviews the neuro-immune-endocrine physiology of the skin responsible for its multiple functions and the extreme disturbances of the healing process, like the excess and deficiency of the extracellular matrix deposition. PMID: 19722029 [PubMed - in process] |
| Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis.
September 2, 2009 at 6:29 am
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| | Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis. J Reprod Dev. 2009 Aug;55(4):351-5 Authors: Suzuki M, Lee HC, Kayasuga Y, Chiba S, Nedachi T, Matsuwaki T, Yamanouchi K, Nishihara M Progranulin (PGRN) is a growth modulating factor released by a variety of cells. This molecule has gained the attention of the neuroscience community with recent discoveries of multifunctional roles of PGRN in normal brain and neurodegenerative disorders. We focus on novel roles of PGRN as a sex steroid-responsible gene in the developing and adult rodent brain. While the developing brain is feminine by default, hormone exposure, including androgen and estrogen, induces masculinization during the critical period. We have shown that PGRN is a sex steroid-responsible gene that may be involved in masculinization of the perinatal rat brain. We also found that in adult rats PGRN gene expression was up-regulated by estrogen in the hippocampus, suggesting that PGRN may mediate the mitogenic effects of estrogen in the active area of neurogenesis. Since it has been recently reported that mutations in PGRN gene are responsible for a type of frontotemporal lobar degeneration in humans, PGRN appears to be also involved in modulating neurodegeneration. Together, PGRN gene expression is induced by estrogen in both developing and adult brains, and it may play multifunctional roles in the organization of functional masculinization in the developing brain and the maintenance of adult brain function. PMID: 19721334 [PubMed - in process] |
| Drag reducing polymers improve tissue perfusion via modification of the RBC traffic in microvessels.
September 2, 2009 at 6:29 am
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| | Drag reducing polymers improve tissue perfusion via modification of the RBC traffic in microvessels. Biorheology. 2009;46(4):281-92 Authors: Marhefka JN, Zhao R, Wu ZJ, Velankar SS, Antaki JF, Kameneva MV This paper reports a novel, physiologically significant, microfluidic phenomenon generated by nanomolar concentrations of drag-reducing polymers (DRP) dissolved in flowing blood, which may explain previously demonstrated beneficial effects of DRP on tissue perfusion. In microfluidic systems used in this study, DRP additives were found to significantly modify traffic of red blood cells (RBC) into microchannel branches as well as reduce the near-wall cell-free layer, which normally is found in microvessels with a diameter smaller than 0.3 mm. The reduction in plasma layer size led to attenuation of the so-called "plasma skimming" effect at microchannel bifurcations, increasing the number of RBC entering branches. In vivo, these changes in RBC traffic may facilitate gas transport by increasing the near vessel wall concentration of RBC and capillary hematocrit. In addition, an increase in near-wall viscosity due to the redirection of RBC in this region may potentially decrease vascular resistance as a result of increased wall shear stress, which promotes endothelium mediated vasodilation. These microcirculatory phenomena can explain the previously reported beneficial effects of DRP on hemodynamics in vivo observed in many animal studies. We also report here our finding that DRP additives reduce flow separations at microchannel expansions, deflecting RBC closer to the wall and eliminating the plasma recirculation zone. Although the exact mechanism of the DRP effects on RBC traffic in microchannels is yet to be elucidated, these findings may further DRP progress toward clinical use. PMID: 19721190 [PubMed - in process] |
| Regenerative pharmacology for diabetes mellitus.
September 2, 2009 at 6:29 am
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| | Regenerative pharmacology for diabetes mellitus. Mol Interv. 2009 Aug;9(4):171-4 Authors: Furth ME, Christ GJ PMID: 19720749 [PubMed - in process] |
| Influence of ethanol on the release of growth factors in human blood-derived platelet gels.
September 2, 2009 at 6:29 am
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| | Influence of ethanol on the release of growth factors in human blood-derived platelet gels. Biologicals. 2009 Aug 29; Authors: Kuo YP, Lee YL, Tseng YH, Su CH, Burnouf T, Su CY Platelet gels (PG) are new topical single-donor blood products which are attracting great interest in regenerative medicine. They are obtained by mixing a platelet-rich plasma fraction with thrombin to generate a fibrin gel enriched in platelet growth factors (GF). The type of thrombin preparation may affect PG reproducibility. We have determined the impact of 14.6% (v/v) ethanol-stabilized thrombin (EHT) on the release of GF by platelets. Various ratios of EHT and platelet concentrates were mixed to obtain from 2.43 to 7.96% ethanol concentration. Platelet-derived growth factor-AB (PDGF-AB), transforming growth factor-ss1 (TGF-ss1), vascular endothelium growth factor (VEGF), epidermal growth factor (EGF), and insulin-like growth factor-1 (IGF-1) were assessed at 5, 120, and 300min after PG formation. Protein profiles of thrombin and PG releasates were analyzed by SDS-PAGE. The amount of PDGF-AB, TGF-ss1, and VEGF released per platelet decreased significantly (p<0.05) with increasing ethanol concentrations but, however, not that of EGF. IGF-1 content was stable, consistent with its presence mostly in plasma. SDS-PAGE indicated that ethanol did not affect fibrin formation. In conclusion, ethanol has a significant impact on the amount of GF released by platelets and should be strictly controlled to standardize PG and optimize clinical benefits. PMID: 19720546 [PubMed - as supplied by publisher] |
| Differential cytotoxic effects of mono-(2-ethylhexyl) phthalate on blastomere-derived embryonic stem cells and differentiating neurons.
September 2, 2009 at 6:29 am
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| | Differential cytotoxic effects of mono-(2-ethylhexyl) phthalate on blastomere-derived embryonic stem cells and differentiating neurons. Toxicology. 2009 Aug 28; Authors: Lim CK, Kim SK, Ko DS, Cho JW, Jun JH, An SY, Han JH, Kim JH, Yoon YD Potential applications of embryonic stem (ES) cells are not limited to regenerative medicine but can also include in vitro screening of various toxicants. In this study, we established mouse ES cell lines from isolated blastomeres of two-cell stage embryos and examined their potential use as an in vitro system for the study of developmental toxicity. Two ES cell lines were established from 69 blastomere-derived blastocysts (2.9%). The blastomere-derived ES (bm-ES) cells were treated with mono-(2-ethylhexyl) phthalate (MEHP) in an undifferentiated state or after directed differentiation into early neural cell types. We observed significantly decreased cell viability when undifferentiated bm-ES cells were exposed to a high dose of MEHP (1,000muM). The cytotoxic effects of MEHP were accompanied by increased DNA fragmentation, nuclear condensation, and activation of Caspase-3, which are biochemical and morphological features of apoptosis. Compared to undifferentiated bm-ES cells, considerably lower doses of MEHP (50 and 100muM) were sufficient to induce cell death in early neurons differentiated from bm-ES cells. At the lower doses, the number of neural cells positive for the active form of Caspase-3 was greater than that for undifferentiated bm-ES cells. Thus, our data indicate that differentiating neurons are more sensitive to MEHP than undifferentiated ES cells, and that undifferentiated ES cells may have more efficient defense systems against cytotoxic stresses. These findings might contribute to the development of a new predictive screening method for assessment of hazards for developmental toxicity. PMID: 19720108 [PubMed - as supplied by publisher] |
| Generation of functional neural artificial tissue from human umbilical cord blood stem cells.
September 2, 2009 at 6:29 am
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| | Generation of functional neural artificial tissue from human umbilical cord blood stem cells. Tissue Eng Part C Methods. 2009 Sep;15(3):365-72 Authors: Jurga M, Lipkowski AW, Lukomska B, Buzanska L, Kurzepa K, Sobanski T, Habich A, Coecke S, Gajkowska B, Domanska-Janik K Stem cell-based regenerative neurology is an emerging concept for treatment of diseases of central nervous system. Among variety of proposed procedures, one of the most promising is refilling of cystic cavities of injured brain parenchyma with artificial neural tissue. Recent studies revealed that after allogenic transplantation in rodents these tissue-engineered entities were shown efficient in repair of hypoxic/ischemic brain injury. Human umbilical cord blood (HUCB) was recognized to be an efficient and noncontroversial source of neural stem cells (NSC). The main purpose of this study was to generate HUCB-derived neural artificial tissue and investigate their functional properties. Neural organoids formed on human-originated biodegradable scaffolds within 3 weeks and resembled niche structure where immature stem cells (Oct4+ and Sox2+) and proliferating neuroblasts (Nestin+, GFAP+, and Ki67+) were present. Such aggregates were placed on multi-electrode chips and differentiated toward mature neurons (TUJ1+ and MAP2+). These three-dimensional aggregates in contrast to two-dimensional cultures formed functional circuits and generated spontaneous field/action potentials. Our results indicate that three-dimensional environment facilitates maturation of HUCB-derived NSC what should be considered regarding regenerative medicine application. PMID: 19719393 [PubMed - in process] | 
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