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| Stem Cell Agency Calls Off Budget Session: No Public Info Available
June 9, 2010 at 7:30 PM
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| The California stem cell agency today cancelled its Thursday review of its proposed budget for the next fiscal year after it failed to supply any information to the public on the spending plan.
The agency did not offer any explanation for the postponement of the meeting of the directors' Finance Subcommittee. Don Gibbons, CIRM's chief communications officer, also did not respond to a query early | | |
| Automated Info from CIRM
June 9, 2010 at 9:39 AM
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| For those of you who want information directly from the California stem cell agency, here is a link to a list of the RSS feeds that CIRM provides.
Using the RSS process will send press releases, announcements(which sometimes are news worthy) and meeting agendas automatically to your computer. | | |
| Endogenous lung stem cells: what is their potential for use in regenerative medicine?
June 9, 2010 at 7:24 AM
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| | Endogenous lung stem cells: what is their potential for use in regenerative medicine? Expert Rev Respir Med. 2010 Jun;4(3):349-62 Authors: Bertoncello I, McQualter JL Advances in stem cell technologies in recent years have generated considerable interest in harnessing the potential of adult and embryonic stem cells in regenerative medicine. Stem cell-based therapies are a particularly attractive option for the treatment of intractable lung diseases for which current therapies are essentially palliative. Proof-of-principle experiments in animal models demonstrate the efficacy of exogenous stem cells in mediating lung repair by attenuating fibrotic responses to injury, but also suggest that their ability to contribute to lung epithelial regeneration and repair is limited. Consequently, attention has turned to endogenous lung stem cells as targets or vehicles for the delivery of lung regenerative therapies. In this article, we discuss the potential and promise of endogenous lung stem cells in regenerative medicine, and the problems and challenges faced by researchers and clinicians in harnessing their potential to repair the lung. PMID: 20524918 [PubMed - in process] | | |
| Advances in biomimetic and nanostructured biohybrid materials.
June 9, 2010 at 7:24 AM
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| | Advances in biomimetic and nanostructured biohybrid materials. Adv Mater. 2010 Jan 19;22(3):323-36 Authors: Ruiz-Hitzky E, Darder M, Aranda P, Ariga K The rapid increase of interest in the field of biohybrid and biomimetic materials that exhibit improved structural and functional properties is attracting more and more researchers from life science, materials science, and nanoscience. Concomitant results offer valuable opportunities for applications that involve disciplines dealing with engineering, biotechnology, medicine and pharmacy, agriculture, nanotechnology, and others. In the current contribution we collect recent illustrative examples of assemblies between materials of biological origin and inorganic solids of different characteristics (texture, structure, and particle size). We introduce here a general overview on strategies for the preparation and conformation of biohybrids, the synergistic effects that determine the final properties of these materials, and their diverse applications, which cover areas as different as tissue engineering, drug delivery systems, biosensing devices, biocatalysis, green nanocomposites, etc. PMID: 20217713 [PubMed - indexed for MEDLINE] | | |
| Clinical impact of suicide gene therapy in allogeneic hematopoietic stem cell transplantation.
June 9, 2010 at 7:24 AM
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| | Clinical impact of suicide gene therapy in allogeneic hematopoietic stem cell transplantation. Hum Gene Ther. 2010 Mar;21(3):241-50 Authors: Lupo-Stanghellini MT, Provasi E, Bondanza A, Ciceri F, Bordignon C, Bonini C Allogeneic hematopoietic stem cell transplantation (allo-SCT) from an HLA-matched related or unrelated donor is a curative option for patients with high-risk hematological diseases. In the absence of a matched donor, patients have been offered investigational transplantation strategies such as umbilical cord blood SCT or family haploidentical SCT. Besides the activity of the conditioning regimen, most of the antileukemic potential of allo-SCT relies on alloreactivity, promoted by donor lymphocytes reacting against patient-specific antigens, such as minor and major histocompatibility antigens, ultimately translating into cancer immunotherapy. Unfortunately, alloreactivity is also responsible for the most serious and frequent complication of allo-SCT: graft-versus-host-disease (GvHD). The risk of GvHD increases with the level of HLA disparity between host and donor, and leads to impaired quality of life and reduced survival expectancy, particularly among patients receiving transplants from HLA-mismatched donors. Gene transfer technologies are promising tools to manipulate donor T cell immunity to enforce the graft-versus-tumor effect, to promote functional immune reconstitution (graft vs. infection), and to prevent or control GvHD. To this purpose, several cell and gene transfer approaches have been investigated at the preclinical level, and are being implemented in clinical trials. Suicide gene therapy is to date the most extensive clinical application of T cell-based gene therapy. In several phase I-II clinical studies conducted worldwide this approach proved highly feasible, safe, and effective in promoting a dynamic and patient-specific modulation of alloreactivity. This review focuses on this approach. PMID: 20121594 [PubMed - indexed for MEDLINE] | | |
| Dynamic 3D culture promotes spontaneous embryonic stem cell differentiation in vitro.
June 9, 2010 at 7:24 AM
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| | Dynamic 3D culture promotes spontaneous embryonic stem cell differentiation in vitro. Tissue Eng Part C Methods. 2010 Feb;16(1):115-21 Authors: Gerlach JC, Hout M, Edsbagge J, Björquist P, Lübberstedt M, Miki T, Stachelscheid H, Schmelzer E, Schatten G, Zeilinger K Spontaneous in vitro differentiation of mouse embryonic stem cells (mESC) is promoted by a dynamic, three-dimensional (3D), tissue-density perfusion technique with continuous medium perfusion and exchange in a novel four-compartment, interwoven capillary bioreactor. We compared ectodermal, endodermal, and mesodermal immunoreactive tissue structures formed by mESC at culture day 10 with mouse fetal tissue development at gestational day E9.5. The results show that the bioreactor cultures more closely resemble mouse fetal tissue development at gestational day E9.5 than control mESC cultured in Petri dishes. PMID: 19382830 [PubMed - indexed for MEDLINE] | | |
| Use of iodixanol self-generated density gradients to enrich for viable urothelial cells from nonneurogenic and neurogenic bladder tissue.
June 9, 2010 at 7:24 AM
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| | Use of iodixanol self-generated density gradients to enrich for viable urothelial cells from nonneurogenic and neurogenic bladder tissue. Tissue Eng Part C Methods. 2010 Feb;16(1):33-40 Authors: Bruce AT, Sangha N, Richmond A, Johnson K, Jones S, Spencer T, Ludlow JW Suspensions of viable urothelial cells (UC) isolated from patient bladder biopsies often contain considerable amounts of extraneous materials comprised of cellular debris, dead and dying UC, and red blood cells. We have consistently observed an inversely proportional relationship between UC attachment efficiency and the amount of extraneous materials in the suspension; viable UC cell attachment efficiency decreases as the amount of extraneous materials in the cell suspension increases. Processing the initial cell isolate to reduce the amount of extraneous materials can enrich for viable UC capable of attaching and proliferating in ex vivo cultures. In this report, we describe the isolation of an enriched population of viable UC from nonneurogenic and neurogenic bladder tissue biopsies using iodixanol self-generated density gradients (OptiPrep), and characterization by trypan blue exclusion, fluorescence-activated cell sorting, immunofluorescence, and growth kinetics. PMID: 19351240 [PubMed - indexed for MEDLINE] | | |
| Design and development of a novel biostretch apparatus for tissue engineering.
June 9, 2010 at 7:13 AM
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| | Design and development of a novel biostretch apparatus for tissue engineering. J Biomech Eng. 2010 Jan;132(1):014503 Authors: Pang Q, Zu JW, Siu GM, Li RK A uniaxial cyclic stretch apparatus is designed and developed for tissue engineering research. The biostretch apparatus employs noncontact electromagnetic force to uniaxially stretch a rectangular Gelfoam or RTV silicon scaffold. A reliable controller is implemented to control four stretch parameters independently: extent, frequency, pattern, and duration of the stretch. The noncontact driving force together with the specially designed mount allow researchers to use standard Petri dishes and commercially available CO(2) incubators to culture an engineered tissue patch under well-defined mechanical conditions. The culture process is greatly simplified over existing processes. Further, beyond traditional uniaxial stretch apparatuses, which provide stretch by fixing one side of the scaffolds and stretching the other side, the new apparatus can also apply uniaxial stretch from both ends simultaneously. Using the biostretch apparatus, the distributions of the strain on the Gelfoam and GE RTV 6166 silicon scaffolds are quantitatively analyzed. PMID: 20524751 [PubMed - in process] | | |
| Biodegradation of porous calcium phosphate scaffolds in an ectopic bone formation model studied by X-ray computed microtomograph.
June 9, 2010 at 7:13 AM
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| | Biodegradation of porous calcium phosphate scaffolds in an ectopic bone formation model studied by X-ray computed microtomograph. Eur Cell Mater. 2010;19:136-46 Authors: Komlev VS, Mastrogiacomo M, Pereira RC, Peyrin F, Rustichelli F, Cancedda R Three types of ceramic scaffolds with different composition and structure [namely synthetic 100% hydroxyapatite (HA; Engipore), synthetic calcium phosphate multiphase biomaterial containing 67% silicon stabilized tricalcium phosphate (Si-TCP; Skelite) and natural bone mineral derived scaffolds (Bio-oss)] were seeded with mesenchymal stem cells (MSC) and ectopically implanted for 8 and 16 weeks in immunodeficient mice. X-ray synchrotron radiation microtomography was used to derive 3D structural information on the same scaffolds both before and after implantation. Meaningful images and morphometric parameters such as scaffold and bone volume fraction, mean thickness and thickness distribution of the different phases as a function of the implantation time, were obtained. The used imaging algorithms allowed a direct comparison and registration of the 3D structure before and after implantation of the same sub-volume of a given scaffold. In this way it was possible to directly monitor the tissue engineered bone growth and the complete or partial degradation of the scaffold. Further, the detailed kinetics studies on Skelite scaffolds implanted for different length of times from 3 days to 24 weeks, revealed in the X-ray absorption histograms two separate peaks associated to HA and TCP. It was therefore possible to observe that the progressive degradation of the Skelite scaffolds was mainly due to the resorption of TCP. The different saturation times in the tissue engineered bone growth and in the TCP resorption confirmed that the bone growth was not limited the scaffold regions that were resorbed but continued in the inward direction with respect to the pore surface. PMID: 20349404 [PubMed - indexed for MEDLINE] | | |
| Advancing towards a tissue-engineered tympanic membrane: silk fibroin as a substratum for growing human eardrum keratinocytes.
June 9, 2010 at 7:13 AM
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| | Advancing towards a tissue-engineered tympanic membrane: silk fibroin as a substratum for growing human eardrum keratinocytes. J Biomater Appl. 2010 Mar;24(7):591-606 Authors: Ghassemifar R, Redmond S, Zainuddin , Chirila TV Human tympanic membrane cells (hTMCs), harvested from tympanic membrane (TM) explants, were grown in culture and then seeded on membranes prepared from silkworm (Bombyx mori) silk fibroin (BMSF) and on tissue-culture plastic membranes (PET). Fibroin was isolated from silk cast into membranes with a thickness of 10-15 microm. The hTMCs were cultured on both materials for 15 days in a serum-containing culture medium. The cells grown on both substrata were subjected to nuclear staining (DAPI) and counted. Further, the cultures were immunostained for a number of protein markers related to the epithelial/keratinocyte phenotype and cell adhesion complexes. The BMSF membranes supported levels of hTMC growth higher than that observed on the PET membranes. The immunofluorochemical analysis indicated unequivocally that BMSF is a more suitable substratum than PET with respect to the growth patterns, proliferation, and cell-cell contact and adhesion. BMSF appear as a promising substratum in the tissue-engineered constructs for the replacement of TM in case of nonhealing perforations. PMID: 20308345 [PubMed - indexed for MEDLINE] | | |
| Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue.
June 9, 2010 at 7:13 AM
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| | Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue. Eur Cell Mater. 2010;19:127-35 Authors: Müller AM, Mehrkens A, Schäfer DJ, Jaquiery C, Güven S, Lehmicke M, Martinetti R, Farhadi I, Jakob M, Scherberich A, Martin I Grafts generated by cultivation of progenitor cells from the stromal vascular fraction of human adipose tissue have been proven to have osteogenic and vasculogenic properties in vivo. However, in vitro manufacture of such implants is challenged by complex, impractical and expensive processes, and requires implantation in a separate surgery. This study investigates the feasibility of an intraoperative approach to engineer cell-based bone grafts with tissue harvest, cell isolation, cell seeding onto a scaffold and subsequent implantation within a few hours. Freshly isolated adipose tissue cells from a total of 11 donors, containing variable fractions of mesenchymal and endothelial progenitors, were embedded at different densities in a fibrin hydrogel, which was wrapped around bone substitute materials based on beta-tricalcium phosphate (ChronOS), hydroxyapatite (Engipore), or acellular xenograft (Bio-Oss). The resulting constructs, generated within 3 hours from biopsy harvest, were immediately implanted ectopically in nude mice and analysed after eight weeks. All explants contained blood vessels formed by human endothelial cells, functionally connected to the recipient's vasculature. Human origin cells were also found within osteoid structures, positively immunostained for bone sialoprotein and osteocalcin. However, even with the highest loaded cell densities, no frank bone tissue was detected, independently of the material used. These results provide a proof-of-principle that an intraoperative engineering of autologous cell-based vasculogenic bone substitutes is feasible, but highlight that - in the absence of in vitro commitment--additional cues (e.g., low dose of osteogenic factors or orthotopic environmental conditions) are likely needed to support complete osteoblastic cell differentiation and bone tissue generation. PMID: 20198567 [PubMed - indexed for MEDLINE] | | |
| [Repair non-healing wound with artificial dermis and autologous skin graft]
June 9, 2010 at 7:13 AM
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| | [Repair non-healing wound with artificial dermis and autologous skin graft] Zhonghua Shao Shang Za Zhi. 2009 Dec;25(6):444-7 Authors: Chen X, Wang XJ, Wang C, Chen H, Zhang GA OBJECTIVE: To observe the feasibility of repairing non-healing wound with artificial dermis and autologous skin graft, and to evaluate its efficacy. METHODS: Twenty in-patients with 25 non-healing wounds lasting more than 8 weeks were divided into chronic ulcer group (9 patients with 11 ulcerating scars after trauma and burn), and bone exposing group (11 patients with 14 wounds with exposed bone ranging from 0.8 - 77.0 cm(2) in size, the largest 22.0 cm x 3.5 cm). Wounds were debrided and repaired with artificial dermis in the first stage. Autologous split-thickness skin was grafted in the II stage when the wounds were well vascularized locally and exposed bone and tendon were covered with dermis-like tissue within 2 - 6 weeks. RESULTS: In chronic ulcer group, 9 of the 11 wounds healed well, the other 2 healed after routine dressing change. In bone exposing group, 12 of the 14 wounds healed well and the exposed bone was effectively covered; artificial dermis on the other 2 wounds failed to survive due to infection, and they were repaired with skin flap later. Patients were followed up for 5 - 24 months. Wounds healed with satisfactory appearance and no recurrence of wound or obvious hyperplasic scar was observed; no obvious scar was observed in the donor site. CONCLUSIONS: The method of repairing non-healing wound with artificial dermis combining with autologous skin graft is simple; and it results in healing of wounds with high quality and little damage to the donor site. It provides a new choice for repairing non-healing wound. PMID: 20193168 [PubMed - indexed for MEDLINE] | | |
| Quantitative ultrasound biomicroscopy for the analysis of healthy and repair cartilage tissue.
June 9, 2010 at 7:13 AM
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| | Quantitative ultrasound biomicroscopy for the analysis of healthy and repair cartilage tissue. Eur Cell Mater. 2010;19:58-71 Authors: Gelse K, Olk A, Eichhorn S, Swoboda B, Schoene M, Raum K The increasing spectrum of different cartilage repair strategies requires the introduction of adequate non-destructive methods to analyse their outcome in-vivo, i.e. arthroscopically. The validity of non-destructive quantitative ultrasound biomicroscopy (UBM) was investigated in knee joints of five miniature pigs. After 12 weeks, six 5-mm defects, treated with different cartilage repair approaches, provided tissues with different structural qualities. Healthy articular cartilage from each contralateral unoperated knee joint served as a control. The reflected and backscattered ultrasound signals were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB) parameters. The cartilage repair tissues were additionally assessed biomechanically by cyclic indentation, histomorphologically and immunohistochemically. UBM allowed high-resolution visualisation of the structure of the joint surface and subchondral bone plate, as well as determination of the cartilage thickness and demonstrated distinct differences between healthy cartilage and the different repair cartilage tissues with significant higher IRC values and a steeper negative slope of the depth-dependent backscatter amplitude AIBslope for healthy cartilage. Multimodal analyses revealed associations between IRC and the indentation stiffness. Furthermore, AIBslope and AIB at the cartilage-bone boundary (AIBdC) were associated with the quality of the repair matrices and the subchondral bone plate, respectively. This ex-vivo pilot study confirms that UBM can provide detailed imaging of articular cartilage and the subchondral bone interface also in repaired cartilage defects, and furthermore, contributes in certain aspects to a basal functional characterization of various forms of cartilage repair tissues. UBM could be further established to be applied arthroscopically in-vivo. PMID: 20186666 [PubMed - indexed for MEDLINE] | | |
| VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo.
June 9, 2010 at 7:13 AM
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| | VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo. Eur Cell Mater. 2010;19:30-40 Authors: Wernike E, Montjovent MO, Liu Y, Wismeijer D, Hunziker EB, Siebenrock KA, Hofstetter W, Klenke FM Bone formation and osseointegration of biomaterials are dependent on angiogenesis and vascularization. Angiogenic growth factors such as vascular endothelial growth factor (VEGF) were shown to promote biomaterial vascularization and enhance bone formation. However, high local concentrations of VEGF induce the formation of malformed, nonfunctional vessels. We hypothesized that a continuous delivery of low concentrations of VEGF from calcium phosphate ceramics may increase the efficacy of VEGF administration.VEGF was co-precipitated onto biphasic calcium phosphate (BCP) ceramics to achieve a sustained release of the growth factor. The co-precipitation efficacy and the release kinetics of the protein were investigated in vitro. For in vivo investigations BCP ceramics were implanted into critical size cranial defects in Balb/c mice. Angiogenesis and microvascularization were investigated over 28 days by means of intravital microscopy. The formation of new bone was determined histomorphometrically. Co-precipitation reduced the burst release of VEGF. Furthermore, a sustained, cell-mediated release of low concentrations of VEGF from BCP ceramics was mediated by resorbing osteoclasts. In vivo, sustained delivery of VEGF achieved by protein co-precipitation promoted biomaterial vascularization, osseointegration, and bone formation. Short-term release of VEGF following superficial adsorption resulted in a temporally restricted promotion of angiogenesis and did not enhance bone formation. The release kinetics of VEGF appears to be an important factor in the promotion of biomaterial vascularization and bone formation. Sustained release of VEGF increased the efficacy of VEGF delivery demonstrating that a prolonged bioavailability of low concentrations of VEGF is beneficial for bone regeneration. PMID: 20178096 [PubMed - indexed for MEDLINE] | | |
| [Treatment for osteonecrosis of femoral head by hVEGF-165 gene modified marrow stromal stem cells under arthroscope]
June 9, 2010 at 7:13 AM
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| | [Treatment for osteonecrosis of femoral head by hVEGF-165 gene modified marrow stromal stem cells under arthroscope] Zhonghua Yi Xue Za Zhi. 2009 Oct 13;89(37):2629-33 Authors: Liu BY, Zhao DW OBJECTIVE: To understand the biological characteristics and osteogenic potential of hVEGF-165 gene modified marrow stromal stem cells and investigate the effect and value of treatment for osteonecrosis of femoral head by hVEGF-165 gene modified marrow stromal stem cells under arthroscope. METHODS: rAAV-2-hVEGF-165 plasmids were extracted and transfected into rabbit marrow stromal stem cells. hVEGF-165 mediated by adeno-associated virus (AAV) was used to transfect rMSCs. The transfection efficiency was detected with enhanced green fluorescent protein under fluorescence microscope. hVEGF-165 mediated by adeno-associated virus (AAV) was used to transfect rMSCs. Virus transfection stayed overnight after 90% cell converged. MOI was 105. The transcription and expression of hVEGF-165 protein expression were detected by RT-PCR and Western blot. The necrotic bone was emptied and then MSCs were implanted under arthroscope. The histology of femoral head was inspected at postoperative 2 - 8 weeks. RESULTS: The expression of hVEGF-165 gene could be found distinctly in the transfected rabbit MSCs and hVEGF-165 protein in the supernatants of transfected cell cultures. The transfection efficiency of adeno-associated virus (AAV) transfected rMSCs was 70%. And rAAV-2-hVEGF-165 transfected rMSCs achieved an effective expression by RT-PCR and Western blot. hVEGF-165 could be found after a 48-hour transfection and peaked at Day 10. Immunohistochemical detection showed that the implanted rMSCs was positive at Week 2 and strong positive at Week 8. The compressive strength of the hVEGF-165 gene group approached that of normal control. CONCLUSION: hVEGF-165 gene transfected rabbit MSCs can express hVEGF-165 with highly biological activity. It provides provided a basis for employing hVEGF-165 gene and MSCs based gene therapy for ONFH repairing and regeneration. rAAV-2-hVEGF-165/MSCs may be implanted accurately under arthroscope. Implantation of human BMP-2 gene transfected BMSCs can repair early-stage experimental femoral head necrosis. PMID: 20137681 [PubMed - indexed for MEDLINE] | | |
| Microporous cell-laden hydrogels for engineered tissue constructs.
June 9, 2010 at 7:13 AM
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| | Microporous cell-laden hydrogels for engineered tissue constructs. Biotechnol Bioeng. 2010 May 1;106(1):138-48 Authors: Park JH, Chung BG, Lee WG, Kim J, Brigham MD, Shim J, Lee S, Hwang CM, Durmus NG, Demirci U, Khademhosseini A In this article, we describe an approach to generate microporous cell-laden hydrogels for fabricating biomimetic tissue engineered constructs. Micropores at different length scales were fabricated in cell-laden hydrogels by micromolding fluidic channels and leaching sucrose crystals. Microengineered channels were created within cell-laden hydrogel precursors containing agarose solution mixed with sucrose crystals. The rapid cooling of the agarose solution was used to gel the solution and form micropores in place of the sucrose crystals. The sucrose leaching process generated homogeneously distributed micropores within the gels, while enabling the direct immobilization of cells within the gels. We also characterized the physical, mechanical, and biological properties (i.e., microporosity, diffusivity, and cell viability) of cell-laden agarose gels as a function of engineered porosity. The microporosity was controlled from 0% to 40% and the diffusivity of molecules in the porous agarose gels increased as compared to controls. Furthermore, the viability of human hepatic carcinoma cells that were cultured in microporous agarose gels corresponded to the diffusion profile generated away from the microchannels. Based on their enhanced diffusive properties, microporous cell-laden hydrogels containing a microengineered fluidic channel can be a useful tool for generating tissue structures for regenerative medicine and drug discovery applications. PMID: 20091766 [PubMed - indexed for MEDLINE] | | |
| Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice.
June 9, 2010 at 7:13 AM
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| | Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice. J Hepatol. 2010 Feb;52(2):211-9 Authors: Navarro-Alvarez N, Soto-Gutierrez A, Chen Y, Caballero-Corbalan J, Hassan W, Kobayashi S, Kondo Y, Iwamuro M, Yamamoto K, Kondo E, Tanaka N, Fox IJ, Kobayashi N BACKGROUND & AIMS: Transplantation of isolated hepatocytes holds great promise as an alternative to whole organ liver transplantation. For treatment of liver failure, access to the portal circulation has significant risks and intrahepatic hepatocyte engraftment is poor. In advanced cirrhosis, transplantation into an extrahepatic site is necessary and intrasplenic engraftment is short-lived. Strategies that allow repeated extrahepatic infusion of hepatocytes could improve the efficacy and safety of hepatocyte transplantation for the treatment of liver failure. METHODS: A non-immunogenic self-assembling peptide nanofiber (SAPNF) was developed as a three-dimensional scaffold and combined with growth factors derived from a conditionally immortalized human hepatocyte cell line to engineer a hepatic tissue graft that would allow hepatocyte engraftment outside the liver. RESULTS: The hepatic tissue constructs maintained hepatocyte-specific gene expression and functionality in vitro. When transplanted into skeletal muscle as an extrahepatic site for engraftment, the engineered hepatic grafts provided life-saving support in models of acute, fulminant, and chronic liver failure that recapitulates these clinical diseases. CONCLUSIONS: SAPNF-engineered hepatic constructs engrafted and functioned as hepatic tissues within the muscle to provide life-sustaining liver support. These engineered tissue constructs contained no animal products that would limit their development as a therapeutic approach. PMID: 20022655 [PubMed - indexed for MEDLINE] | | |
| Development and characterization of a three-dimensional organotypic human vaginal epithelial cell model.
June 9, 2010 at 7:13 AM
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| | Development and characterization of a three-dimensional organotypic human vaginal epithelial cell model. Biol Reprod. 2010 Mar;82(3):617-27 Authors: Hjelm BE, Berta AN, Nickerson CA, Arntzen CJ, Herbst-Kralovetz MM We have developed an in vitro human vaginal epithelial cell (EC) model using the innovative rotating wall vessel (RWV) bioreactor technology that recapitulates in vivo structural and functional properties, including a stratified squamous epithelium with microvilli, tight junctions, microfolds, and mucus. This three-dimensional (3-D) vaginal model provides a platform for high-throughput toxicity testing of candidate microbicides targeted to combat sexually transmitted infections, effectively complementing and extending existing testing systems such as surgical explants or animal models. Vaginal ECs were grown on porous, collagen-coated microcarrier beads in a rotating, low fluid-shear environment; use of RWV bioreactor technology generated 3-D vaginal EC aggregates. Immunofluorescence and scanning and transmission electron microscopy confirmed differentiation and polarization of the 3-D EC aggregates among multiple cell layers and identified ultrastructural features important for nutrient absorption, cell-cell interactions, and pathogen defense. After treatment with a variety of toll-like receptor (TLR) agonists, cytokine production was quantified by cytometric bead array, confirming that TLRs 2, 3, 5, and 6 were expressed and functional. The 3-D vaginal aggregates were more resistant to nonoxynol-9 (N-9), a contraceptive and previous microbicide candidate, when compared to two-dimensional monolayers of the same cell line. A dose-dependent production of tumor necrosis factor-related apoptosis-inducing ligand and interleukin-1 receptor antagonist, biomarkers of cervicovaginal inflammation, correlated to microbicide toxicity in the 3-D model following N-9 treatment. These results indicate that this 3-D vaginal model could be used as a complementary tool for screening microbicide compounds for safety and efficacy, thus improving success in clinical trials. PMID: 20007410 [PubMed - indexed for MEDLINE] | | |
| Reconstruction of oviduct and demonstration of epithelial fate determination in mice.
June 9, 2010 at 7:13 AM
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| | Reconstruction of oviduct and demonstration of epithelial fate determination in mice. Biol Reprod. 2010 Mar;82(3):528-33 Authors: Yamanouchi H, Umezu T, Tomooka Y The mouse oviductal epithelium is a simple monolayer until Postnatal Day 7 and subsequently consists of differentiated secretory cells and ciliated cells. In adult oviduct, the two types of epithelial cells are unevenly distributed; ciliated cells are dominant in the ampulla and secretory cells are dominant in the isthmus. Recombinants of enzymatically separated epithelial and mesenchymal tissues of oviducts were grafted under kidney capsule for 4 wk. The recombinants developed structures with a lumen covered with a monolayer of ciliated cells and secretory cells, demonstrating that the recombinant tissues reconstructed oviductal structure. Geographically (ampulla versus isthmus) heterotypic recombinants were prepared from neonatal oviducts at Day 3. The epithelia in reconstructed oviducts took the patterns of cell distribution depending on the origin of the mesenchymal tissues. The results indicate that the mesenchyme geographically has distinct abilities to determine undifferentiated epithelial cells to ciliated cells or secretory cells in the mouse oviduct. PMID: 19906687 [PubMed - indexed for MEDLINE] | | |
| CIRM and Aussie Hopes
June 8, 2010 at 10:57 PM
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| Earlier today we carried an item about the hope of some Australian stem cell researchers that California would come to their financial aid.
We queried CIRM concerning the news report. Don Gibbons, CIRM's chief communications officer, replied,
"We are in discussion with the the Australian MRC regarding a potential
agreement like the one we have already for the state of Victoria. It would
be bound | | | | 
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