|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | In vitro hydrolytic and enzymatic degradation of nestlike-patterned electrospun poly(D,L-lactide-co-glycolide) scaffolds. J Biomed Mater Res A. 2010 Aug 19; Authors: Zhou X, Cai Q, Yan N, Deng X, Yang X A common problem in applying electrospun biodegradable polyester matrixes as tissue-engineering scaffolds is their serious shrinkage with degradation to reduce the porosity drastically. To ameliorate this problem, a nestlike-patterned poly(D,L-lactide-co-glycolide) (PLGA) nanofibrous ( approximately 900 nm) matrix was proposed and fabricated by electropinning. Shrinkage studies demonstrated that the dimension change of nestlike-patterned fibrous membrane was much smaller than those of nonwoven and parallel-aligned fibrous membranes. And the robust framework of the patterned matrix helped to maintain its original nestlike topographical structure during degradation. Compared to hydrolytic-degraded specimens, the PLGA nanofibrous matrixes degraded in the presence of lysozyme showed larger weight loss but slower decrease in molecular weight. Besides, porous fibers with intact surface were detected by scanning electron microscopy after 20-week hydrolysis, and fibers with pores both inside and on surface were observed after enzymatic degradation for 12 weeks. Accordingly, the former presented a bimodal gel permeation chromatography (GPC) peak, while no bi or multimodal GPC peaks were found for the latter as degradation proceeded. These results indicated that an acid autocatalytic effect still existed in the hydrolysis of PLGA nanofibrous matrix. The presence of lysozyme could only accelerate the dissolution of degradation products with low molecular weight, but have no contribution to the chain scission. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20725988 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro evaluation of polyester-based scaffolds seeded with adipose derived stem cells for peripheral nerve regeneration. J Biomed Mater Res A. 2010 Aug 19; Authors: Tse KH, Sun M, Mantovani C, Terenghi G, Downes S, Kingham PJ To overcome the disadvantages of autografts for peripheral nerve repair, different methods such as artificial nerve conduits have been investigated for an alternative approach. This study demonstrated that solvent casting is a simple but efficient method to create thin polyester-based scaffolds for stem cell delivery. Using poly (epsilon-caprolactone) and poly (D,L-lactic acid), we produced scaffold films containing heterogenous depressions (pits) on the air surface with a size ranging from 0.5 to 30 mum(2). These scaffolds were moderately hydrophobic; however, they supported the differentiation of adipose derived stem cells (ADSC) into a Schwann cell-like phenotype. The differentiated ADSC (dADSC) expressed S100 protein and glial fibrillary acidic protein and readily adhered to the films and proliferated at a similar rate to those cultured on tissue culture polystyrene. Cells were also positive for proliferating cell nuclear antigen. Furthermore, dADSC retained functional activity and significantly enhanced neurite outgrowth from dorsal root ganglia neurons. This study suggests polymer scaffolds combined with dADSCs could be a promising therapy for peripheral nerve injuries. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20725987 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vivo evaluation of MMP sensitive high-molecular weight HA-based hydrogels for bone tissue engineering. J Biomed Mater Res A. 2010 Aug 19; Authors: Kim J, Kim IS, Cho TH, Kim HC, Yoon SJ, Choi J, Park Y, Sun K, Hwang SJ Hyaluronic acid (170 kDa)-based hydrogel was synthesized using acrylated hyaluronic acid (HA) and matrix metalloproteinase (MMP) sensitive HA-based hydrogels were then prepared by conjugation with two different peptides: cell adhesion peptides containing integrin-binding domains (Arg-Gly-Asp: RGD) and a cross-linker with MMP degradable peptides to mimic the remodeling characteristics of natural extracellular matrices by cell-derived MMPs. Mechanical properties of these hydrogels were evaluated with different weight percentages (2.5 and 3.5 wt %) by measuring elastic modulus, viscous modulus, and swelling ratio. Human mesenchymal stem cells (hMSCs) were then cultured in MMP-sensitive or insensitive HA-based hydrogels and/or immobilized cell adhesive RGD peptides in vitro. Actin staining and image analysis proved that cells cultured in the MMP-sensitive hydrogel with RGD peptides showed extensive cell spreading and sprouting. Gene expression analysis showed that bone specific genes such as alkaline phosphatase, osteocalcin, and osteopontin increased in MMP-sensitive hydrogels as biomolecules such as BMPs and cells were added in the gels. For in vivo calvarial defect regeneration, five different samples (MMP insensitive hydrogel, MMP sensitive hydrogel, MMP sensitive hydrogel with BMP-2, MMP sensitive hydrogel with hMSC, and MMP sensitive hydrogel with BMP-2 and hMSC) were prepared. After 4 weeks of implantation, the Masson-Trichrome staining and micro computed tomography scan results demonstrated that the MMP sensitive hydrogels with BMP-2 and hMSCs have the highest mature bone formation. The MMP sensitive HA-based hydrogel could become useful scaffolds in bone tissue engineering with improvements on tissue remodeling rates and regeneration activity. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20725983 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mono-dispersed bioactive glass nanospheres: Preparation and effects on biomechanics of mammalian cells. J Biomed Mater Res A. 2010 Aug 19; Authors: Hong Z, Luz GM, Hampel PJ, Jin M, Liu A, Chen X, Mano JF Mono-dispersed SiO(2)-CaO bioactive glass nanospheres (BGNS) were prepared by a two step sol-gel method in the absence of surfactant. The size of BGNS ranged from 200 to 350 nm in diameter and exhibited a rough surface texture. In vitro biomineralization tests showed that BGNS could rapidly induce the deposition of an apatite layer in simulated body fluid (SBF). The effect of bioactive glass on the biomechanical properties of various mammalian cells was first reported in this paper. Atomic force microscopy (AFM) was used for measuring the biomechanical properties of mammalian cells. The result showed that BGNS-medium could significantly decrease the plasma membrane stiffness of bone marrow stem cells (BMSCs) by approximately 50% and stimulate BMSCs spreading. The effect of BGNS on biomechanical properties of bovine aortic endothelial cells (BAECs) was opposite to that on BMSCs. BGNS increased the BAECs' stiffness and stimulated the elongation of endothelial cells and the formation of endothelial networks, which might potentially facilitate the vascularization of implanted BGNS-based biomaterials in tissue engineering as a scaffold or as an injectable system. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20725980 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of dense polylactic acid/beta-tricalcium phosphate scaffolds for bone tissue engineering. J Biomed Mater Res A. 2010 Aug 19; Authors: Yanoso-Scholl L, Jacobson JA, Bradica G, Lerner AL, O'Keefe RJ, Schwarz EM, Zuscik MJ, Awad HA Advances in biomaterial fabrication have introduced numerous innovations in designing scaffolds for bone tissue engineering. Often, the focus has been on fabricating scaffolds with high and interconnected porosity that would allow for cellular seeding and tissue ingrowth. However, such scaffolds typically lack the mechanical strength to sustain in vivo ambulatory stresses in models of load bearing cortical bone reconstruction. In this study, we investigated the microstructural and mechanical properties of dense PLA and PLA/beta-TCP (85:15) scaffolds fabricated using a rapid volume expansion phase separation technique, which embeds uncoated beta-TCP particles within the porous polymer. PLA scaffolds had a volumetric porosity in the range of 30 to 40%. With the embedding of beta-TCP mineral particles, the porosity of the scaffolds was reduced in half, whereas the ultimate compressive and torsional strength were significantly increased. We also investigated the properties of the scaffolds as delivery vehicles for growth factors in vitro and in vivo. The low-surface porosity resulted in sub optimal retention efficiency of the growth factors, and burst release kinetics reflecting surface coating rather than volumetric entrapment, regardless of the scaffold used. When loaded with BMP2 and VEGF and implanted in the quadriceps muscle, PLA/beta-TCP scaffolds did not induce ectopic mineralization but induced a significant 1.8-fold increase in neo vessel formation. In conclusion, dense PLA/beta-TCP scaffolds can be engineered with enhanced mechanical properties and potentially be exploited for localized therapeutic factor delivery. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20725979 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Novel three-dimensional scaffolds of poly(L-lactic acid) microfibers using electrospinning and mechanical expansion: Fabrication and bone regeneration. J Biomed Mater Res B Appl Biomater. 2010 Aug 19; Authors: Shim IK, Jung MR, Kim KH, Seol YJ, Park YJ, Park WH, Lee SJ Poly(L-lactic acid) (PLLA) microfibrous scaffolds with three-dimensional (3D) structures were fabricated using an electrospinning technique with a subsequent mechanical expansion process. To achieve a 3D fibrous structure, the fusion at the contact points of the as-spun PLLA microfibers was avoided using an appropriate binary solvent system of methylene chloride and acetone. The solvent composition was optimized based on the solvent power, volatility, and viscosity (methylene chloride:acetone = 9:1 volume ratio). The final 3D structure of the electrospun scaffolds was obtained after mechanical expansion of the electrospun microfibrous mats. The pore sizes of the scaffolds were controlled by varying the degree of expansion of the nonbonded microfibrous mats, and they were in the range of several microns up to 400 mum. The 3D scaffolds were examined for their morphological properties and their potential use for the proliferation of osteoblasts. Generally recognized electrospun 2D nanofibrous membranes were also tested in order to compare the cell behaviors using different scaffold geometries. The 3D scaffolds demonstrated a high level of osteoblast proliferation (1.8-fold higher than nanofibrous membranes in a week). The osteoblasts actively penetrated the inside of the 3D scaffold and showed a spatial cell distribution, as confirmed by SEM and H&E staining, while a monolayer formed in the case of the 2D nanofibrous membranes with limited cell infiltration. In vivo results further showed that 3D electrospun microfibrous matrices were a favorable substrate for cell infiltration and bone formation after 2 and 4 weeks, using a rabbit calvarial defect model. In this study, the 3D microfibrous PLLA scaffolds fabricated using electrospinning techniques might be an innovative addition to tissue engineering applications. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20725960 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Silk hydrogel for cartilage tissue engineering. J Biomed Mater Res B Appl Biomater. 2010 Aug 19; Authors: Chao PH, Yodmuang S, Wang X, Sun L, Kaplan DL, Vunjak-Novakovic G Cartilage tissue engineering based on cultivation of immature chondrocytes in agarose hydrogel can yield tissue constructs with biomechanical properties comparable to native cartilage. However, agarose is immunogenic and nondegradable, and our capability to modify the structure, composition, and mechanical properties of this material is rather limited. In contrast, silk hydrogel is biocompatible and biodegradable, and it can be produced using a water-based method without organic solvents that enables precise control of structural and mechanical properties in a range of interest for cartilage tissue engineering. We observed that one particular preparation of silk hydrogel yielded cartilaginous constructs with biochemical content and mechanical properties matching constructs based on agarose. This finding and the possibility to vary the properties of silk hydrogel motivated this study of the factors underlying the suitability of hydrogels for cartilage tissue engineering. We present data resulting from a systematic variation of silk hydrogel properties, silk extraction method, gel concentration, and gel structure. Data suggest that silk hydrogel can be used as a tool for studies of the hydrogel-related factors and mechanisms involved in cartilage formation, as well as a tailorable and fully degradable scaffold for cartilage tissue engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20725950 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Prediction of osteoconductive activity of modified potassium fluorrichterite glass-ceramics by immersion in simulated body fluid. J Mater Sci Mater Med. 2010 Aug 20; Authors: Bhakta S, Pattanayak DK, Takadama H, Kokubo T, Miller CA, Mirsaneh M, Reaney IM, Brook I, van Noort R, Hatton PV Potassium fluorrichterite (KNaCaMg(5)Si(8)O(22)F(2)) glass-ceramics were modified by either increasing the concentration of calcium (GC5) or by the addition of P(2)O(5) (GP2). The stoichiometric composition (GST), GC5 and GP2 were soaked in simulated body fluid (SBF) along with 45S5-type bioglass as a control. After immersion, surface analyses were performed using thin-film X-ray diffraction (TF-XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared (reflection) spectroscopy (FT-IR). All compositions showed the formation of a calcium phosphate rich surface layer in SBF; GST, GP2 and the bioglass control within 7 days of immersion and GC5 after 14 days. It was concluded that all compositions were likely to be osteoconductive in vivo, with GP2 providing the best performance in terms of the combination of rapid formation of the surface layer and superior mechanical properties. This glass-ceramic system has potential as a load bearing bioceramic for fabrication of medical devices intended for skeletal tissue repair. PMID: 20725768 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Sacral neuromodulations for female lower urinary tract, pelvic floor, and bowel disorders. Curr Opin Obstet Gynecol. 2010 Aug 18; Authors: Wehbe SA, Whitmore K, Ho MH PURPOSE OF REVIEW: In recent years, sacral neuromodulation (SNM) has been investigated for the treatment of various types of lower urinary tract and bowel dysfunctions. This review discusses recently published data related to the therapeutic applications of SNM in female lower urinary tract, pelvic floor, and bowel disorders. RECENT FINDINGS: SNM has been employed initially in the treatment of refractory idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. Since then, several studies, including randomized and controlled trials, have confirmed the therapeutic effects of SNM in these disorders. The applications of SNM are now extended to the treatment of other female pelvic problems, such as fecal incontinence, chronic constipation, interstitial cystitis/painful bladder syndrome, sexual dysfunction, and neurogenic disorders, with similar promising results. SUMMARY: SNM is approved by the Food and Drug Administration for the treatment of idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. SNM is not yet an approved method for the treatment of other pelvic disorders, but data supporting its benefit are emerging. The major advantage of SNM lies in its potential to treat the bladder, urethral sphincter, anal sphincters, and pelvic floor muscles simultaneously, which might result in better therapeutic effects. PMID: 20724927 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Nanosilver as a new generation of nanoproduct in biomedical applications. Trends Biotechnol. 2010 Aug 17; Authors: Chaloupka K, Malam Y, Seifalian AM Nanosilver (NS), comprising silver nanoparticles, is attracting interest for a range of biomedical applications owing to its potent antibacterial activity. It has recently been demonstrated that NS has useful anti-inflammatory effects and improves wound healing, which could be exploited in developing better dressings for wounds and burns. The key to its broad-acting and potent antibacterial activity is the multifaceted mechanism by which NS acts on microbes. This is utilized in antibacterial coatings on medical devices to reduce nosocomial infection rates. Many new synthesis methods have emerged and are being evaluated for NS production for medical applications. NS toxicity is also critically discussed to reflect on potential concerns before widespread application in the medical field. PMID: 20724010 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Visual Enhancement of Laparoscopic Partial Nephrectomy With 3-Charge Coupled Device Camera: Assessing Intraoperative Tissue Perfusion and Vascular Anatomy by Visible Hemoglobin Spectral Response. J Urol. 2010 Aug 17; Authors: Crane NJ, Gillern SM, Tajkarimi K, Levin IW, Pinto PA, Elster EA PURPOSE: We report the novel use of 3-charge coupled device camera technology to infer tissue oxygenation. The technique can aid surgeons to reliably differentiate vascular structures and noninvasively assess laparoscopic intraoperative changes in renal tissue perfusion during and after warm ischemia. MATERIALS AND METHODS: We analyzed select digital video images from 10 laparoscopic partial nephrectomies for their individual 3-charge coupled device response. We enhanced surgical images by subtracting the red charge coupled device response from the blue response and overlaying the calculated image on the original image. Mean intensity values for regions of interest were compared and used to differentiate arterial and venous vasculature, and ischemic and nonischemic renal parenchyma. RESULTS: The 3-charge coupled device enhanced images clearly delineated the vessels in all cases. Arteries were indicated by an intense red color while veins were shown in blue. Differences in mean regions of interest intensity values for arteries and veins were statistically significant (p >0.0001). Three-charge coupled device analysis of pre-clamp and post-clamp renal images revealed visible, dramatic color enhancement for ischemic vs nonischemic kidneys. Differences in the mean regions of interest intensity values were also significant (p <0.05). CONCLUSIONS: We present a simple use of conventional 3-charge coupled device camera technology in a way that may provide urological surgeons with the ability to reliably distinguish vascular structures during hilar dissection, and detect and monitor changes in renal tissue perfusion during and after warm ischemia. PMID: 20723937 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Vitamin D(3) metabolites induce osteogenic differentiation in human dental pulp and human dental follicle cells. J Steroid Biochem Mol Biol. 2010 Aug 16; Authors: Khanna-Jain R, Vuorinen A, Sándor GK, Suuronen R, Miettinen S Vitamin D(3) metabolites regulate the bone metabolism and 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) is known to play an important role in teeth mineralization. However, little is known about the potential of vitamin D as an osteogenic inducer in human dental pulp (hDPCs) and dental follicle cells (hDFCs) in vitro. Therefore, we investigated the effects of vitamin D(3) metabolites 1alpha,25(OH)(2)D(3) and 25-hydroxyvitamin D(3) (25OHD(3)) [10] G.E. Wise, S. Frazier-Bowers and R.N. D'Souza, Cellular, molecular, and genetic determinants of tooth eruption, Crit. Rev. Oral. Biol. Med. 13 (2002), pp. 323-334. View Record in Scopus | Cited By in Scopus (55on proliferation and osteogenic differentiation of hDPCs and hDFCs in vitro. We also examined whether vitamin D(3) metabolic enzymes were regulated in hDFCs and hDPCs. Cell proliferation was decreased by both metabolites in hDPCs and hDFCs. Vitamin D(3) metabolites increased ALP activity and induced mineralization when osteogenic supplements (OS; L-ascorbic acid-2-phosphate+beta- glycerophosphate) were added, though the expression of osteocalcin (OC) and osteopontin (OPN) were regulated without the addition of OS. CYP24 and CYP27B1 expressions were upregulated by vitamin D(3) metabolites and 25OHD(3) was converted into 1alpha,25(OH)(2)D(3) in the culture medium. These results confirm that 1alpha,25(OH)(2)D(3) (10nM, 100nM) and 25OHD(3) (500nM) can be used as osteogenic inducers synergistically with osteogenic supplements for differentiation of hDPCs and hDFCs. Furthermore, our findings strengthen our knowledge about the role of hDPCs and hDFCs as vitamin D(3) target cells. PMID: 20723601 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Strengthen researches on translational medicine and regenerative medicine in burns.] Zhonghua Shao Shang Za Zhi. 2010 Jun;26(3):167-9 Authors: Huang YS Translational medicine and regenerative medicine are presently the hottest areas in medical research. Translational medicine is regarded as a two-way model of medical research, i.e. bench to bedside and bedside to bench. The purpose of translational research is to test novel therapeutic strategies developed through experimentation in human beings, and to facilitate the transformation of findings resulting from basic research to clinical practice. Regenerative medicine is to search for effective biotherapy methods to promote self repair and regeneration; or to construct new tissues and organs to improve or restore the function of the injured tissues and organs. To strengthen researches on translational medicine and regenerative medicine in burns may promote the application of new clinical therapeutic strategies, and supply effective therapeutic measures for treatment of severe burns. PMID: 20723416 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Erythropoietin gene-modified conditioned medium of human mesenchymal cells promotes hematopoietic development from human embryonic stem cells.] Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Jul;18(4):976-80 Authors: Yang C, Ji L, Yue W, Wang RY, Li YH, Xi JF, Xie XY, He LJ, Nan X, Pei XT The study was aimed to investigate the effect of deriving hematopoietic cells from human embryonic stem cells (hESCs) by the erythropoietin gene-modified conditioned medium of human mesenchymal cells. The mesenchymal stem cells (MSCs) steadily expressing EPO were established by lentiviral system. The expression of exogenous EPO was detected by RT-PCR and Western blot. After suspension culture, hESCs developed into embryonic bodies (EBs). Then the EB cells were cultured in conditional medium. The hESCs-derived hematopoietic cells were analyzed by immunofluorescence, CFU assay and RT-PCR. The results indicated that the exogenous EPO successfully expressed in the EPO transfected MSCs (EPO/MSCs). The supernatant from EPO/MSCs increased CD34(+) cell population and the expression of globin, and enhanced colony forming unit incidence. These effects were obviously higher than that of control. It is concluded that the EPO gene-modified conditioned medium of human mesenchymal cells can induce the hESCs to differentiate into hematopoietic cells. PMID: 20723312 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Unravelling the development of the visual cortex: implications for plasticity and repair. J Anat. 2010 Aug 16; Authors: Bourne JA Abstract The visual cortex comprises over 50 areas in the human, each with a specified role and distinct physiology, connectivity and cellular morphology. How these individual areas emerge during development still remains something of a mystery and, although much attention has been paid to the initial stages of the development of the visual cortex, especially its lamination, very little is known about the mechanisms responsible for the arealization and functional organization of this region of the brain. In recent years we have started to discover that it is the interplay of intrinsic (molecular) and extrinsic (afferent connections) cues that are responsible for the maturation of individual areas, and that there is a spatiotemporal sequence in the maturation of the primary visual cortex (striate cortex, V1) and the multiple extrastriate/association areas. Studies in both humans and non-human primates have started to highlight the specific neural underpinnings responsible for the maturation of the visual cortex, and how experience-dependent plasticity and perturbations to the visual system can impact upon its normal development. Furthermore, damage to specific nuclei of the visual cortex, such as the primary visual cortex (V1), is a common occurrence as a result of a stroke, neurotrauma, disease or hypoxia in both neonates and adults alike. However, the consequences of a focal injury differ between the immature and adult brain, with the immature brain demonstrating a higher level of functional resilience. With better techniques for examining specific molecular and connectional changes, we are now starting to uncover the mechanisms responsible for the increased neural plasticity that leads to significant recovery following injury during this early phase of life. Further advances in our understanding of postnatal development/maturation and plasticity observed during early life could offer new strategies to improve outcomes by recapitulating aspects of the developmental program in the adult brain. PMID: 20722872 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell-mediated neuroprotection in a mouse model of human tauopathy. J Neurosci. 2010 Jul 28;30(30):9973-83 Authors: Hampton DW, Webber DJ, Bilican B, Goedert M, Spillantini MG, Chandran S Tau protein in a hyperphosphorylated state makes up the intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease and cases of frontotemporal dementia. Mutations in Tau cause familial forms of frontotemporal dementia, establishing that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. Transgenic mice expressing human mutant tau in neurons exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments composed of hyperphosphorylated tau. Here we show that a previously described mouse line transgenic for human P301S tau exhibits an age-related, layer-specific loss of superficial cortical neurons, similar to what has been observed in human frontotemporal dementias. We also show that focal neural precursor cell implantation, resulting in glial cell differentiation, leads to the sustained rescue of cortical neurons. Together with evidence indicating that astrocyte transplantation may be neuroprotective, our findings suggest a beneficial role for glial cell-based repair in neurodegenerative diseases. PMID: 20668182 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Histological and immunohistochemical characteristics of stimulated angiogenesis in transplantation of multipotent stem cells derived from the adipose tissue in patients with chronic ischemia of the extremities] Klin Khir. 2010 May;(5):40-3 Authors: Poliachenko IuV, Driuk MF, Dombrovs'kyÄ DB The cellular technologies application with the objective for the processes of angiogenesis stimulation, in the ischemia conditions, constitutes an actual task for modern stage of a science development, the discovery of a new sources of cells-stimulants for neoangiogenesis is in a progress. The investigation was performed with an objective of studying of histological and immunohistochemical changes in muscular tissue, occurring after autotransplantation of multipotent stromal cells from adipose tissue of the patients, suffering the extremity ischemia. Histological and immunohistochemical investigations (detection of antibodies expression towards Villebrand factor, collagen type IV and vimentin) of processes, occurring in muscular tissue after introduction of multipotent stromal cells from adipose tissue of this patient, were conducted. The reduction of myofibrils ischemic affection and rapid activation of the muscle regenerative potential were shown. There was established a vivid stimulation of the angiogenesis processes during already first month after cellular transplantation performance. PMID: 20623978 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The influence of bioreactor geometry and the mechanical environment on engineered tissues. J Biomech Eng. 2010 May;132(5):051006 Authors: Osborne JM, O'Dea RD, Whiteley JP, Byrne HM, Waters SL A three phase model for the growth of a tissue construct within a perfusion bioreactor is examined. The cell population (and attendant extracellular matrix), culture medium, and porous scaffold are treated as distinct phases. The bioreactor system is represented by a two-dimensional channel containing a cell-seeded rigid porous scaffold (tissue construct), which is perfused with a culture medium. Through the prescription of appropriate functional forms for cell proliferation and extracellular matrix deposition rates, the model is used to compare the influence of cell density-, pressure-, and culture medium shear stress-regulated growth on the composition of the engineered tissue. The governing equations are derived in O'Dea et al. "A Three Phase Model for Tissue Construct Growth in a Perfusion Bioreactor," Math. Med. Biol., in which the long-wavelength limit was exploited to aid analysis; here, finite element methods are used to construct two-dimensional solutions to the governing equations and to investigate thoroughly their behavior. Comparison of the total tissue yield and averaged pressures, velocities, and shear stress demonstrates that quantitative agreement between the two-dimensional and long-wavelength approximation solutions is obtained for channel aspect ratios of order 10(-2) and that much of the qualitative behavior of the model is captured in the long-wavelength limit, even for relatively large channel aspect ratios. However, we demonstrate that in order to capture accurately the effect of mechanotransduction mechanisms on tissue construct growth, spatial effects in at least two dimensions must be included due to the inherent spatial variation of mechanical stimuli relevant to perfusion bioreactors, most notably, fluid shear stress, a feature not captured in the long-wavelength limit. PMID: 20459207 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Immunohistochemical study of oral epithelial sheets cultured on amniotic membrane for oral mucosal reconstruction. Biomed Mater Eng. 2010 Jan;20(1):37-45 Authors: Amemiya T, Nakamura T, Yamamoto T, Kinoshita S, Kanamura N We immunohistochemically evaluated whether oral epithelial cells grown on amniotic membrane (AM) would be an effective biomaterial for reconstructing oral mucosal defects. Oral mucosal epithelial cells from albino rabbits were grown for 2-3 weeks on an AM carrier in a co-culture with 3T3 fibroblasts. The rabbits' oral mucosal defects were reconstructed by autologous transplantation of the oral epithelial sheets. The oral epithelial sheets and reconstructed tissues were then examined histologically and immunohistochemically. After 2-3 weeks of culture, the rabbit oral mucosal epithelial cells developed 5-7 layers of stratification on the AM. Immunohistochemistry revealed that they expressed keratins 4/13, integrin alpha 6, alpha 5 chain and collagen type III, but not keratins 1/10. The transplanted sheets attached to the mucosal defects, and AM fragments disappeared from the transplant area. Immunohistochemical patterns revealed properties of the mucous membrane and basement membrane components in the reconstructed epithelia. The results of this experiment showed that the AM-cultured oral epithelial sheets resulted in mucosa-like differentiation, and adhered to the mucosal defects. Therefore, AM-cultured oral epithelial sheets might be a useful biomaterial for oral mucosal reconstruction. PMID: 20448302 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Preparation and evaluation of microporous organogel scaffolds for cell viability and proliferation. Colloids Surf B Biointerfaces. 2010 Aug 1;79(1):105-12 Authors: Lukyanova L, Franceschi-Messant S, Vicendo P, Perez E, Rico-Lattes I, Weinkamer R Various porous scaffolds utilizing an organogel were prepared by particulate-leaching method. The porous organogels were made of biodegradable, non-toxic ingredients like soybean oil or caprylic/capric triglyceride as the organic liquids and 12-hydroxystearic acid as the gelator. The scaffolds possessed an effective porosity of 56-65%, and good pore interconnectivity with an average pore size from 220 to 290mum. The biodegradability of such materials was evaluated and lipases were able to totally degrade the scaffolds. The porosity of the material associated with high draining led to suitable scaffolds which were evaluated for CHO cell viability and proliferation using the MTT test. This evaluation was performed over a period of 3 weeks and showed a greater ability to promote cell proliferation for the soybean oil based scaffold than for the caprylic/capric triglyceride one. The histological investigations revealed that this scaffold was able to promote cell colonization and attachment and could induce the production of collagen. PMID: 20427161 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Molecular assembly and biological activity of a recombinant fragment of fibronectin (FNIII(7-10)) on poly(ethyl acrylate). Colloids Surf B Biointerfaces. 2010 Jul 1;78(2):310-6 Authors: Rico P, González-GarcÃa C, Petrie TA, GarcÃa AJ, Salmerón-Sánchez M Fibronectin (FN) fibrillogenesis is a cell-mediated process involving integrin activation that results in conformational changes of FN molecules and the organization of actin cytoskeleton. A similar process can be induced by some particular chemistries in the absence of cells, e.g., poly(ethyl acrylate) (PEA), which enhance FN-FN interactions leading to the formation of a biologically active network on the material surface. We have investigated the organization of a recombinant fragment of fibronectin (FNIII(7-10)) upon adsorption on this particular chemistry, PEA. Atomic force microscopy (AFM) was used to identify individual molecules of the fragment after adsorption, as well as the evolution of the distribution of adsorbed molecules on the surface of the material as the concentration of the adsorbing solution increased. Globular molecules that turn into small aggregates were found as a function of solution concentration. Above a threshold concentration of the adsorbing solution (50 microg/mL) an interconnected network of the FNIII(7-10) fragment is obtained on the material surface. The bioavailability of specific cell adhesion domains, including RGD, within the molecules was higher on PEA than on the control glass. The biological activity of the fragment was further investigated by evaluating focal adhesion formation and actin cytoskeleton for MC3T3-E1 osteoblast-like cells. Well-developed focal adhesion complexes and insertions of actin stress fibers were found on PEA in a similar way as it happens in the control SAM-OH. Moreover, increasing the hydrophilicity of the surface by incorporating -OH groups led to globular molecules of the fragment homogeneously distributed throughout the surface; and the cell-material interaction is reduced as depicted by the lack of well-developed focal plaques and actin cytoskeleton. PMID: 20409696 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Correlation of cell strain in single osteocytes with intracellular calcium, but not intracellular nitric oxide, in response to fluid flow. J Biomech. 2010 May 28;43(8):1560-4 Authors: Rath AL, Bonewald LF, Ling J, Jiang JX, Van Dyke ME, Nicolella DP Osteocytes compose 90-95% of all bone cells and are the mechanosensors of bone. In this study, the strain experienced by individual osteocytes resulting from an applied fluid flow shear stress was quantified and correlated to two biological responses measured in real-time within the same individual osteocytes: (1) the upregulation of intracellular calcium and (2) changes in intracellular nitric oxide. Osteocyte-like MLO-Y4 cells were loaded with Fluo-4 AM and DAR-4M and exposed to uniform laminar fluid flow shear stresses of 2, 8, or 16 dyn/cm(2). Intracellular calcium and nitric oxide changes were determined by measuring the difference in fluorescence intensity from the cell's basal level prior to fluid flow and the level immediately following exposure. Individual cell strains were calculated using digital image correlation. MLO-Y4 cells showed a linear increase in cell strain, intracellular calcium concentration, and nitric oxide concentration with an increase in applied fluid flow rate. The increase in intracellular calcium was well correlated to the strain that each cell experienced. This study shows that osteocytes exposed to the same fluid flow experienced a range of individual strains and changes in intracellular calcium and nitric oxide concentrations, and the changes in intracellular calcium were correlated with cell strain. These results are among the first to establish a relationship between the strain experienced by osteocytes in response to fluid flow shear and a biological response at the single cell level. Mechanosensing and chemical signaling in osteocytes has been hypothesized to occur at the single cell level, making it imperative to understand the biological response of the individual cell. PMID: 20189178 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects. J Orthop Res. 2010 Sep;28(9):1193-9 Authors: Oliveira JT, Gardel LS, Rada T, Martins L, Gomes ME, Reis RL In this work, the ability of gellan gum hydrogels coupled with autologous cells to regenerate rabbit full-thickness articular cartilage defects was tested. Five study groups were defined: (a) gellan gum with encapsulated chondrogenic predifferentiated rabbit adipose stem cells (ASC + GF); (b) gellan gum with encapsulated nonchondrogenic predifferentiated rabbit adipose stem cells (ASC); (c) gellan gum with encapsulated rabbit articular chondrocytes (AC) (standard control); (d) gellan gum alone (control); (e) empty defect (control). Full-thickness articular cartilage defects were created and the gellan gum constructs were injected and left for 8 weeks. The macroscopic aspect of the explants showed a progressive increase of similarity with the lateral native cartilage, stable integration at the defect site, more pronouncedly in the cell-loaded constructs. Tissue scoring showed that ASC + GF exhibited the best results regarding tissue quality progression. Alcian blue retrieved similar results with a better outcome for the cell-loaded constructs. Regarding real-time PCR analyses, ASC + GF had the best progression with an upregulation of collagen type II and aggrecan, and a downregulation of collagen type I. Gellan gum hydrogels combined with autologous cells constitute a promising approach for the treatment of articular cartilage defects, and adipose derived cells may constitute a valid alternative to currently used articular chondrocytes. PMID: 20187118 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cell therapy for diabetes: stem cells, progenitors or beta-cell replication? Mol Cell Endocrinol. 2010 Jul 8;323(1):55-61 Authors: Gonez LJ, Knight KR The cure for type 1 diabetes (T1D) will require either the replacement or regeneration of insulin-producing cells, together with measures that prevent their immune-mediated destruction. Experiments in rodent models have found that pancreatic stem cells, committed progenitors and replicating beta-cells can all contribute to insulin-producing cell regeneration. The cellular and molecular mechanisms of these cells, both in vitro and in vivo, have been investigated by us and by others. Furthermore, our surgical research laboratory has developed a unique in vivo chamber model of T1D, allowing the assessment of the behaviour of different sources of insulin-producing cells with a view to their potential use in cell-based therapies. PMID: 20026173 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A Quality Risk Management Model Approach for Cell Therapy Manufacturing. Risk Anal. 2010 Aug 17; Authors: Lopez F, Bartolo CD, Piazza T, Passannanti A, Gerlach JC, Gridelli B, Triolo F International regulatory authorities view risk management as an essential production need for the development of innovative, somatic cell-based therapies in regenerative medicine. The available risk management guidelines, however, provide little guidance on specific risk analysis approaches and procedures applicable in clinical cell therapy manufacturing. This raises a number of problems. Cell manufacturing is a poorly automated process, prone to operator-introduced variations, and affected by heterogeneity of the processed organs/tissues and lot-dependent variability of reagent (e.g., collagenase) efficiency. In this study, the principal challenges faced in a cell-based product manufacturing context (i.e., high dependence on human intervention and absence of reference standards for acceptable risk levels) are identified and addressed, and a risk management model approach applicable to manufacturing of cells for clinical use is described for the first time. The use of the heuristic and pseudo-quantitative failure mode and effect analysis/failure mode and critical effect analysis risk analysis technique associated with direct estimation of severity, occurrence, and detection is, in this specific context, as effective as, but more efficient than, the analytic hierarchy process. Moreover, a severity/occurrence matrix and Pareto analysis can be successfully adopted to identify priority failure modes on which to act to mitigate risks. The application of this approach to clinical cell therapy manufacturing in regenerative medicine is also discussed. PMID: 20723148 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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