| Osiris Therapeutics to Present at ThinkEquity and UBS Conferences
September 11, 2009 at 6:28 pm
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| When proteins change partners
September 11, 2009 at 1:28 pm
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| Stem Cell Therapeutics Corp. Announces Dr. V. Wee Yong's Presentation at the 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis
September 11, 2009 at 10:28 am
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| Hyaluronan benzyl ester as a scaffold for tissue engineering.
September 11, 2009 at 7:47 am
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| | Hyaluronan benzyl ester as a scaffold for tissue engineering. Int J Mol Sci. 2009 Jun;10(7):2972-85 Authors: Vindigni V, Cortivo R, Iacobellis L, Abatangelo G, Zavan B Tissue engineering is a multidisciplinary field focused on in vitro reconstruction of mammalian tissues. In order to allow a similar three-dimensional organization of in vitro cultured cells, biocompatible scaffolds are needed. This need has provided immense momentum for research on "smart scaffolds" for use in cell culture. One of the most promising materials for tissue engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester of hyaluronan (HYAFF((R))). HYAFF((R)) can be processed to obtain several types of devices such as tubes, membranes, non-woven fabrics, gauzes, and sponges. All these scaffolds are highly biocompatible. In the human body they do not elicit any adverse reactions and are resorbed by the host tissues. Human hepatocytes, dermal fibroblasts and keratinocytes, chondrocytes, Schwann cells, bone marrow derived mesenchymal stem cells and adipose tissue derived mesenchymal stem cells have been successfully cultured in these meshes. The same scaffolds, in tube meshes, has been applied for vascular tissue engineering that has emerged as a promising technology for the design of an ideal, responsive, living conduit with properties similar to that of native tissue. PMID: 19742179 [PubMed - in process] |
| PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.
September 11, 2009 at 7:47 am
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| | PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration. Gene Ther. 2009 Sep 10; Authors: Chang PC, Seol YJ, Cirelli JA, Pellegrini G, Jin Q, Franco LM, Goldstein SA, Chandler LA, Sosnowski B, Giannobile WV Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5 x 10(8) or 5.5 x 10(9) pfu ml(-1)), Ad encoding luciferase (Ad-Luc; 5.5 x 10(9) pfu ml(-1); control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg ml(-1)). Bone repair and osseointegration were measured through backscattered scanning electron microscopy, histomorphometry, micro-computed tomography and biomechanical assessments. Furthermore, a panel of local and systemic safety assessments was performed. Results indicated that bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared with Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B shows regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable with rhPDGF-BB protein delivery in vivo.Gene Therapy advance online publication, 10 September 2009; doi:10.1038/gt.2009.117. PMID: 19741730 [PubMed - as supplied by publisher] |
| Hyaluronic acid and chitosan-DNA complex multilayered thin film as surface-mediated nonviral gene delivery system.
September 11, 2009 at 7:47 am
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| | Hyaluronic acid and chitosan-DNA complex multilayered thin film as surface-mediated nonviral gene delivery system. Colloids Surf B Biointerfaces. 2009 Aug 3; Authors: Lin QK, Ren KF, Ji J Sustained release of DNA from the surface of materials represents a promising approach to combine the gene therapy and implantable biomaterials. The nonviral chitosan-DNA complexes were incorporated into the multilayer via layer-by-layer deposition with hyaluronic acid (HA). The UV-vis spectroscopy and atomic force microscopy (AFM) results showed the successful construction of the nonviral complex contained multilayers. The complexes were releasable in physiological condition and a sustained release manner was gained when the multilayer was crosslinked. The cell viability test and the gene transfection assay showed that the natural polyelectrolyte-based nonviral complex incorporated multilayer not only had good cytocompatibility, but also possessed the in vitro gene transfection ability. This kind of surface-mediated nonviral complex incorporated multilayer may have great potential in the localized and controlled delivery of DNA in biomedical implants and tissue engineering application. PMID: 19740634 [PubMed - as supplied by publisher] |
| Scalable Stirred-suspension Bioreactor Culture of Human Pluripotent Stem Cells.
September 11, 2009 at 7:47 am
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| | Scalable Stirred-suspension Bioreactor Culture of Human Pluripotent Stem Cells. Tissue Eng Part A. 2009 Sep 9; Authors: Kehoe DE, Jing D, Lock LT, Tzanakakis EM Advances in stem cell biology have afforded promising results for the generation of various cell types for therapies against devastating diseases. However, a prerequisite for realizing the therapeutic potential of stem cells is the development of bioprocesses for the production of stem cell progeny in quantities that satisfy clinical demands. Recent reports on the expansion and directed differentiation of human embryonic stem cells (hESCs) in scalable stirred-suspension bioreactors (SSBs) demonstrate that large-scale production of therapeutically useful hESC progeny is feasible with current state-of-the-art culture technologies. Stem cells have been cultured in SSBs as aggregates, in microcarrier suspension and after encapsulation. The various modes in which SSBs can be employed for the cultivation of hESCs and human induced pluripotent stem cells (hiPSCs) are described. To that end, this is the first account of hiPSC cultivation in a microcarrier stirred-suspension system. Given that cultured stem cells and their differentiated progeny are the actual products used in tissue engineering and cell therapies, the impact of bioreactor operating conditions on stem cell self-renewal and commitment should be considered. The effects of variables specific to the SSB operation on stem cell physiology are discussed. Finally, major challenges are presented that remain to be addressed before the mainstream use of SSBs for the large-scale culture of hESCs and hiPSCs. PMID: 19739936 [PubMed - as supplied by publisher] |
| Mechanotransductive surfaces for reversible biocatalysis activation.
September 11, 2009 at 7:47 am
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| | Mechanotransductive surfaces for reversible biocatalysis activation. Nat Mater. 2009 Sep;8(9):731-5 Authors: Mertz D, Vogt C, Hemmerlé J, Mutterer J, Ball V, Voegel JC, Schaaf P, Lavalle P Fibronectin, like other proteins involved in mechanotransduction, has the ability to exhibit recognition sites under mechanical stretch. Such cryptic sites are buried inside the protein structure in the native fold and become exposed under an applied force, thereby activating specific signalling pathways. Here, we report the design of new active polymeric nanoassembled surfaces that show some similarities to these cryptic sites. These nanoassemblies consist of a first polyelectrolyte multilayer stratum loaded with enzymes and capped with a second polyelectrolyte multilayer acting as a mechanically sensitive nanobarrier. The biocatalytic activity of the film is switched on/off reversibly by mechanical stretching, which exposes enzymes through the capping barrier, similarly to mechanisms involved in proteins during mechanotransduction. This first example of a new class of biologically inspired surfaces should have great potential in the design of various devices aimed to trigger and modulate chemical reactions by mechanical action with applications in the field of microfluidic devices or mechanically controlled biopatches for example. PMID: 19668209 [PubMed - indexed for MEDLINE] |
| Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation.
September 11, 2009 at 7:47 am
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| | Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation. Nat Mater. 2009 Sep;8(9):763-70 Authors: Gentleman E, Swain RJ, Evans ND, Boonrungsiman S, Jell G, Ball MD, Shean TA, Oyen ML, Porter A, Stevens MM An important aim of regenerative medicine is to restore tissue function with implantable, laboratory-grown constructs that contain tissue-specific cells that replicate the function of their counterparts in the healthy native tissue. It remains unclear, however, whether cells used in bone regeneration applications produce a material that mimics the structural and compositional complexity of native bone. By applying multivariate analysis techniques to micro-Raman spectra of mineralized nodules formed in vitro, we reveal cell-source-dependent differences in interactions between multiple bone-like mineral environments. Although osteoblasts and adult stem cells exhibited bone-specific biological activities and created a material with many of the hallmarks of native bone, the 'bone nodules' formed from embryonic stem cells were an order of magnitude less stiff, and lacked the distinctive nanolevel architecture and complex biomolecular and mineral composition noted in the native tissue. Understanding the biological mechanisms of bone formation in vitro that contribute to cell-source-specific materials differences may facilitate the development of clinically successful engineered bone. PMID: 19633661 [PubMed - indexed for MEDLINE] |
| Regeneration: Recent advances, major puzzles, and biomedical opportunities.
September 11, 2009 at 7:47 am
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| | Regeneration: Recent advances, major puzzles, and biomedical opportunities. Semin Cell Dev Biol. 2009 Jul;20(5):515-6 Authors: Levin M PMID: 19398032 [PubMed - indexed for MEDLINE] |
| Engineered early embryonic cardiac tissue increases cardiomyocyte proliferation by cyclic mechanical stretch via p38-MAP kinase phosphorylation.
September 11, 2009 at 7:47 am
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| | Engineered early embryonic cardiac tissue increases cardiomyocyte proliferation by cyclic mechanical stretch via p38-MAP kinase phosphorylation. Tissue Eng Part A. 2009 Jun;15(6):1373-80 Authors: Clause KC, Tinney JP, Liu LJ, Keller BB, Tobita K Cardiomyocyte (CM) transplantation is one therapeutic option for cardiac repair. Studies suggest that fetal CMs display the best cell type for cardiac repair, which can finitely proliferate, integrate with injured host myocardium, and restore cardiac function. We have recently developed an engineered early embryonic cardiac tissue (EEECT) using embryonic cardiac cells and have shown that EEECT contractile properties and cellular proliferative response to cyclic mechanical stretch stimulation mimic developing fetal myocardium. However, it remains unknown whether cyclic mechanical stretch-mediated high cellular proliferation activity within EEECT reflects CM or non-CM population. Studies have shown that p38-mitogen-activated protein kinase (p38MAPK) plays an important role in both cyclic mechanical stretch stimulation and cellular proliferation. Therefore, in the present study, we tested the hypothesis that cyclic mechanical stretch (0.5 Hz, 5% strain for 48 h) specifically increases EEECT CM proliferation mediated by p38MAPK activity. Cyclic mechanical stretch increased CM, but not non-CM, proliferation and increased p38MAPK phosphorylation. Treatment of EEECT with the p38MAPK inhibitor, SB202190, reduced CM proliferation. The negative CM proliferation effects of SB202190 were not reversed by concurrent stretch stimulation. Results suggest that immature CM proliferation within EEECT can be positively regulated by mechanical stretch and negatively regulated by p38MAPK inhibition. PMID: 19196150 [PubMed - indexed for MEDLINE] |
| Engineering retina from human retinal progenitors (cell lines).
September 11, 2009 at 7:47 am
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| | Engineering retina from human retinal progenitors (cell lines). Tissue Eng Part A. 2009 Jun;15(6):1401-13 Authors: Dutt K, Cao Y Retinal degeneration resulting in the loss of photoreceptors is the leading cause of blindness. Several therapeutic protocols are under consideration for treatment of this disease. Tissue replacement is one such strategy currently being explored. However, availability of tissues for transplant poses a major obstacle. Another strategy with great potential is the use of adult stem cells, which could be expanded in culture and then utilized to engineer retinal tissue. In this study, we have explored a spontaneously immortalized human retinal progenitor cell line for its potential in retinal engineering using rotary cultures to generate three-dimensional (3D) structures. Retinal progenitors cultured alone or cocultured with retinal pigment epithelial cells form aggregates. The aggregate size increases between days 1 and 10. The cells grown as a 3D culture rotary system, which promotes cell-cell interaction, retain a spectrum of differentiation capability. Photoreceptor differentiation in these cultures is confirmed by significant upregulation of rhodopsin and AaNat, an enzyme implicated in melatonin synthesis (immunohistochemistry and Western blot analysis). Photoreceptor induction and differentiation is further attested to by the upregulation of rod transcription factor Nrl, Nr(2)e(3), expression of interstitial retinal binding protein, and rhodopsin kinase by reverse transcription-polymerase chain reaction. Differentiation toward other cell lineages is confirmed by the expression of tyrosine hydroxylase in amacrine cells, thy 1.1 expression in ganglion cells and calbindin, and GNB3 expression in cone cells. The capability of retinal progenitors to give rise to several retinal cell types when grown as aggregated cells in rotary culture offers hope that progenitor stem cells under appropriate culture conditions will be valuable to engineer retinal constructs, which could be further tested for their transplant potential. The fidelity with which this multipotential cell line retains its capacity to differentiate into multiple cell types holds great promise for the use of tissue-specific adult stem cells for therapy. PMID: 19113950 [PubMed - indexed for MEDLINE] |
| Fabrication of the microgrooved/microporous polylactide substrates as peripheral nerve conduits and in vivo evaluation.
September 11, 2009 at 7:47 am
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| | Fabrication of the microgrooved/microporous polylactide substrates as peripheral nerve conduits and in vivo evaluation. Tissue Eng Part A. 2009 Jun;15(6):1381-90 Authors: Hsu SH, Ni HC An innovative technique combining phase transition and microprinting in one step was applied to fabricate the nerve conduits used in peripheral nerve regeneration. The asymmetric microporosity served to generate asymmetric permeability, and the surface microgrooves were introduced to achieve cell alignment in vitro. The symmetric/asymmetric porous poly(D,L-lactide) (PLA) substrates with microgrooves on the surface were tested for their ability to repair 10 mm sciatic nerve transection defects in rats. The in vivo results showed that porous PLA conduits maintained a stable supporting structure during the entire regeneration process. The myelin sheaths of the regenerated nerve in asymmetric conduits were thicker than in symmetric groups at 4 weeks. Moreover, the regenerated nerves in the asymmetric conduits with surface microgrooves had the highest degree of myelination at 4 weeks and the most number of vessels at 6 weeks. The walking track analysis also implied that the asymmetric conduits with surface microgrooves had the highest degree of functional recovery. Based on the study, the combination of microgrooves and asymmetric microporous structure could be employed in the design of nerve conduits for peripheral nerve regeneration in the future. PMID: 19108680 [PubMed - indexed for MEDLINE] |
| Functional improvement of infarcted heart by co-injection of embryonic stem cells with temperature-responsive chitosan hydrogel.
September 11, 2009 at 7:47 am
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| | Functional improvement of infarcted heart by co-injection of embryonic stem cells with temperature-responsive chitosan hydrogel. Tissue Eng Part A. 2009 Jun;15(6):1437-47 Authors: Lu WN, Lü SH, Wang HB, Li DX, Duan CM, Liu ZQ, Hao T, He WJ, Xu B, Fu Q, Song YC, Xie XH, Wang CY Transplantation of embryonic stem cells (ESCs) can improve cardiac function in treatment of myocardial infarction. The low rate of cell retention and survival within the ischemic tissues makes the application of cell transplantation techniques difficult. In this study, we used a temperature-responsive chitosan hydrogel (as scaffold) combined with ESCs to maintain viable cells in the infarcted tissue. Temperature-responsive chitosan hydrogel was prepared and injected into the infarcted heart wall of rat infarction models alone or together with mouse ESCs. The result showed that the 24-h cell retention and 4 week graft size of both groups was significantly greater than with a phosphate buffered saline control. After 4 weeks of implantation, heart function, wall thickness, and microvessel densities within the infarct area improved in the chitosan + ESC, chitosan, and ESC group more than the PBS control. Of the three groups, the chitosan + ESC performed best. Results of this study indicate that temperature-responsive chitosan hydrogel is an injectable scaffold that can be used to deliver stem cells to infarcted myocardium. It can also increase cell retention and graft size. Cardiac function is well preserved, too. PMID: 19061432 [PubMed - indexed for MEDLINE] |
| Engineering the bone-ligament interface using polyethylene glycol diacrylate incorporated with hydroxyapatite.
September 11, 2009 at 7:47 am
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| | Engineering the bone-ligament interface using polyethylene glycol diacrylate incorporated with hydroxyapatite. Tissue Eng Part A. 2009 Jun;15(6):1201-9 Authors: Paxton JZ, Donnelly K, Keatch RP, Baar K Ligaments and tendons have previously been tissue engineered. However, without the bone attachment, implantation of a tissue-engineered ligament would require it to be sutured to the remnant of the injured native tissue. Due to slow repair and remodeling, this would result in a chronically weak tissue that may never return to preinjury function. In contrast, orthopaedic autograft reconstruction of the ligament often uses a bone-to-bone technique for optimal repair. Since bone-to-bone repairs heal better than other methods, implantation of an artificial ligament should also occur from bone-to-bone. The aim of this study was to investigate the use of a poly(ethylene glycol) diacrylate (PEGDA) hydrogel incorporated with hydroxyapatite (HA) and the cell-adhesion peptide RGD (Arg-Gly-Asp) as a material for creating an in vitro tissue interface to engineer intact ligaments (i.e., bone-ligament-bone). Incorporation of HA into PEG hydrogels reduced the swelling ratio but increased mechanical strength and stiffness of the hydrogels. Further, HA addition increased the capacity for cell growth and interface formation. RGD incorporation increased the swelling ratio but decreased mechanical strength and stiffness of the material. Optimum levels of cell attachment were met using a combination of both HA and RGD, but this material had no better mechanical properties than PEG alone. Although adherence of the hydrogels containing HA was achieved, failure occurs at about 4 days with 5% HA. Increasing the proportion of HA improved interface formation; however, with high levels of HA, the PEG HA composite became brittle. This data suggests that HA, by itself or with other materials, might be well suited for engineering the ligament-bone interface. PMID: 18991487 [PubMed - indexed for MEDLINE] |
| Hemodynamics and axial strain additively increase matrix remodeling and MMP-9, but not MMP-2, expression in arteries engineered by directed remodeling.
September 11, 2009 at 7:47 am
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| | Hemodynamics and axial strain additively increase matrix remodeling and MMP-9, but not MMP-2, expression in arteries engineered by directed remodeling. Tissue Eng Part A. 2009 Jun;15(6):1281-90 Authors: Nichol JW, Khan AR, Birbach M, Gaynor JW, Gooch KJ We previously demonstrated the ability to create engineered arteries by carefully controlling the mechanical environment of intact arteries perfused ex vivo, yielding engineered arteries with native appearance and vasoactive response. Increased axial strain was sufficient to increase length up to 20% in 9 days through a growth and remodeling response. The amount of the achievable length increase, however, was highly dependent on the hemodynamic conditions acting through unknown mechanisms. Because matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activity is increased, and often required, in mechanically induced remodeling in vivo, MMP-2 and MMP-9 expression was investigated to elucidate the hemodynamic mediation of artery length. Carotid arteries from 30 kg pigs were perfused for 9 days ex vivo at either in situ axial strain or with a gradual 50% increase in axial strain, under either arterial or reduced hemodynamics ( approximately 10% of arterial hemodynamics). MMP-2 protein expression increased roughly twofold, while MMP-9 expression increased threefold under either reduced hemodynamics or increased axial strain (p < 0.05). The combination of reduced hemodynamics with increased axial strain demonstrated an additive increase in MMP-9 protein (p < 0.05) with no further change in MMP-2 expression. To investigate the mechanism by which axial strain and hemodynamics could additively increase MMP-9 expression, the expression of nuclear factor kappa B (NF-kappaB) subunits p50 and p65 was evaluated. Axial strain stimulated p65 expression and localization, while hemodynamics increased p50 expression, with both molecules being expressed only when both mechanical stimuli were applied. These data suggest that MMP-9 expression can be simultaneously stimulated by separate mechanical stimuli mediated by p50 and p65 expression, and that by using conditions that maximize MMP-9 expression, we can create an optimal remodeling environment to better direct the growth of engineered arteries and other tissues. PMID: 18928401 [PubMed - indexed for MEDLINE] |
| Hyaluronan benzyl ester as a scaffold for tissue engineering.
September 11, 2009 at 7:44 am
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| | Hyaluronan benzyl ester as a scaffold for tissue engineering. Int J Mol Sci. 2009 Jun;10(7):2972-85 Authors: Vindigni V, Cortivo R, Iacobellis L, Abatangelo G, Zavan B Tissue engineering is a multidisciplinary field focused on in vitro reconstruction of mammalian tissues. In order to allow a similar three-dimensional organization of in vitro cultured cells, biocompatible scaffolds are needed. This need has provided immense momentum for research on "smart scaffolds" for use in cell culture. One of the most promising materials for tissue engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester of hyaluronan (HYAFF((R))). HYAFF((R)) can be processed to obtain several types of devices such as tubes, membranes, non-woven fabrics, gauzes, and sponges. All these scaffolds are highly biocompatible. In the human body they do not elicit any adverse reactions and are resorbed by the host tissues. Human hepatocytes, dermal fibroblasts and keratinocytes, chondrocytes, Schwann cells, bone marrow derived mesenchymal stem cells and adipose tissue derived mesenchymal stem cells have been successfully cultured in these meshes. The same scaffolds, in tube meshes, has been applied for vascular tissue engineering that has emerged as a promising technology for the design of an ideal, responsive, living conduit with properties similar to that of native tissue. PMID: 19742179 [PubMed - in process] |
| Gene transfer for erectile dysfunction: will this novel therapy be accepted by urologists?
September 11, 2009 at 7:44 am
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| | Gene transfer for erectile dysfunction: will this novel therapy be accepted by urologists? Curr Opin Urol. 2009 Sep 8; Authors: Melman A, Rojas L, Christ G PURPOSE OF REVIEW: The purpose of this review is to update the results of the only phase 1 erectile dysfunction gene transfer trial and based upon those results present the outcome of a web-based survey that studied whether or not knowledgeable in the field urologists would use gene transfer in their patients once approved for use by the US Food and Drug Administration. RECENT FINDINGS: The results of the clinical trials showed no transfer-related serious adverse events. The response to 10 questions of a web-based survey indicates that gene transfer as a first or second-line therapy for practicing urologists would be well accepted. SUMMARY: Practicing, experienced urologists, after the US Food and Drug Administration approval, are willing to employ gene transfer therapies in their patients, be it men who have failed or dissatisfied with other treatments or as shown in up to one-third of men as a first therapy. That outcome portends for rapid adaptation and active participation into the medical practice for maxi-K or other specific gene transfer, stem cell, or combinations that will be developed in the future. PMID: 19741539 [PubMed - as supplied by publisher] |
| Regeneration: Recent advances, major puzzles, and biomedical opportunities.
September 11, 2009 at 7:44 am
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| | Regeneration: Recent advances, major puzzles, and biomedical opportunities. Semin Cell Dev Biol. 2009 Jul;20(5):515-6 Authors: Levin M PMID: 19398032 [PubMed - indexed for MEDLINE] |
| Fabrication of the microgrooved/microporous polylactide substrates as peripheral nerve conduits and in vivo evaluation.
September 11, 2009 at 7:44 am
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| | Fabrication of the microgrooved/microporous polylactide substrates as peripheral nerve conduits and in vivo evaluation. Tissue Eng Part A. 2009 Jun;15(6):1381-90 Authors: Hsu SH, Ni HC An innovative technique combining phase transition and microprinting in one step was applied to fabricate the nerve conduits used in peripheral nerve regeneration. The asymmetric microporosity served to generate asymmetric permeability, and the surface microgrooves were introduced to achieve cell alignment in vitro. The symmetric/asymmetric porous poly(D,L-lactide) (PLA) substrates with microgrooves on the surface were tested for their ability to repair 10 mm sciatic nerve transection defects in rats. The in vivo results showed that porous PLA conduits maintained a stable supporting structure during the entire regeneration process. The myelin sheaths of the regenerated nerve in asymmetric conduits were thicker than in symmetric groups at 4 weeks. Moreover, the regenerated nerves in the asymmetric conduits with surface microgrooves had the highest degree of myelination at 4 weeks and the most number of vessels at 6 weeks. The walking track analysis also implied that the asymmetric conduits with surface microgrooves had the highest degree of functional recovery. Based on the study, the combination of microgrooves and asymmetric microporous structure could be employed in the design of nerve conduits for peripheral nerve regeneration in the future. PMID: 19108680 [PubMed - indexed for MEDLINE] |
| Autologous stem cell therapy for peripheral arterial disease Meta-analysis and systematic review of the literature.
September 11, 2009 at 7:12 am
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| | Autologous stem cell therapy for peripheral arterial disease Meta-analysis and systematic review of the literature. Atherosclerosis. 2009 Aug 21; Authors: Fadini GP, Agostini C, Avogaro A BACKGROUND: Peripheral arterial disease (PAD) is a common cause of disability and mortality. Up to one third of patients are not susceptible to traditional revascularization and may benefit from stem cell therapies. OBJECTIVE: In this meta-analysis, we sought to determine whether autologous cell therapy is effective in the treatment of PAD. METHODS: We searched the English literature in Medline, Excerpta Medica and the Cochrane database for trials of autologous cell therapy in patients with PAD published before 31 January 2009. We included controlled and non-controlled, randomized and non-randomized trials using autologous bone marrow or granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood cells to treat PAD. We also collected data from trials of G-CSF monotherapy, as a control treatment. RESULTS: In a meta-analysis of 37 trials, autologous cell therapy was effective in improving surrogate indexes of ischemia, subjective symptoms and hard endpoints (ulcer healing and amputation). On the contrary, G-CSF monotherapy was not associated with significant improvement in the same endpoints. Patients with thromboangiitis obliterans showed some larger benefits than patients with atherosclerotic PAD. The intramuscular route of administration and the use of bone marrow cells seemed somehow more effective than intrarterial administration and the use of mobilized peripheral blood cells. The procedures were well tolerated and generally safe. CONCLUSION: This meta-analysis indicates that intramuscular autologous bone marrow cell therapy is a feasible, relatively safe and potentially effective therapeutic strategy for PAD patients, who are not candidate for traditional revascularization. Larger, placebo-controlled, randomized multicenter trials need to be planned and conducted to confirm these findings. PMID: 19740466 [PubMed - as supplied by publisher] | | | 
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