Friday, July 30, 2010

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Geron Go-ahead Rouses Industry and Researchers
July 30, 2010 at 7:03 PM

 

The National Stem Cell Therapy Patient Registry of Malaysia-Measuring Clinical Outcomes of Stem Cell Therapy.
July 30, 2010 at 4:22 PM

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The National Stem Cell Therapy Patient Registry of Malaysia-Measuring Clinical Outcomes of Stem Cell Therapy.

Stem Cell Rev. 2010 Jul 29;

Authors: Loke SC, Chin SP, Sivanandam S, Goh PP, Ng RK, Saw KY, Lim TO

Very few registries worldwide focus on clinical outcomes of stem cell therapy (SCT) as the large number of applications and rapid development of the field complicates registry design considerably. The National Stem Cell Therapy Patient Registry of Malaysia aims to accommodate this by using a main protocol which covers the overall design and administration of the registry, and condition-specific sub-protocols which deal with outcome measures. The registry will start with a few sub-protocols covering existing modes of SCT in Malaysia, with new sub-protocols released periodically as the need arises.

PMID: 20669056 [PubMed - as supplied by publisher]

 

Cardiac stem cell therapy: progress from the bench to bedside.
July 30, 2010 at 4:22 PM

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Cardiac stem cell therapy: progress from the bench to bedside.

Heart. 2010 Jul 28;

Authors: Lovell MJ, Mathur A

In the rush to assess the role of stem cell therapy for cardiovascular disease the details of translation are easily overlooked. This review summarises the progress to date in translating the exciting preclinical results of cardiac repair into man and considers the questions that this area of research has stimulated about the challenges of moving from bench to bedside.

PMID: 20668107 [PubMed - as supplied by publisher]

 

Feasibility of using sodium chloride as a tracer for the characterization of the distribution of matter in complex multi-compartment 3D bioreactors for stem cell culture.
July 30, 2010 at 10:34 AM

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Feasibility of using sodium chloride as a tracer for the characterization of the distribution of matter in complex multi-compartment 3D bioreactors for stem cell culture.

Int J Artif Organs. 2010 Jun;33(6):399-404

Authors: Gerlach JC, Witaschek T, Strobel C, Brayfield CA, Bornemann R, Catapano G, Zeilinger K

The experimental characterization of the distribution of matter in complex multi-compartment three-dimensional membrane bioreactors for human cell culture is complicated by tracer interactions with the membranes and other bioreactor constituents. This is due to the fact that membranes with a high specific surface area often feature a hydrophobic chemical backbone that may adsorb tracers often used to this purpose, such as proteins and dyes. Membrane selectivity, and its worsening caused by protein adsorption, may also hinder tracer transfer across neighboring compartments, thus preventing effective characterization of the distribution of matter in the whole bioreactor. ?Tracer experiments with sodium chloride (NaCl) may overcome some of these limitations and be effectively used to characterize the distribution of matter in complex 3D multi-compartments membrane bioreactors for stem cell culture. NaCl freely permeates most used membranes, it does not adsorb on uncharged membranes, and its concentration may be accurately measured in terms of solution conductivity. In this preliminary study, the feasibility of complex multi-compartment membrane bioreactors was investigated with a NaCl concentration pulse challenge to characterize how their distribution of matter changes when they are operated under different conditions. In particular, bioreactors consisting of three different membrane types stacked on top of one another to form a 3D network were characterized under different feed conditions.

PMID: 20669145 [PubMed - in process]

 

A three-dimensional traction/torsion bioreactor system for tissue engineering.
July 30, 2010 at 10:34 AM

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A three-dimensional traction/torsion bioreactor system for tissue engineering.

Int J Artif Organs. 2010 Jun;33(6):362-9

Authors: Scaglione S, Zerega B, Badano R, Benatti U, Fato M, Quarto R

Purpose: The aim of this study was to design, develop and validate a simple, compact bioreactor system for tissue engineering. The resulting bioreactor was designed to achieve ease-of-use and low costs for automated cell-culturing procedures onto three-dimensional scaffolds under controlled torsion/traction regimes. ?Methods: Highly porous poly-caprolactone-based scaffolds were used as substrates colonized by fibroblast cells (3T3 cell line). Constructs were placed within the cylindrical culture chamber, clumped at the ends and exposed to controlled sequences of torsional stimuli (forward/back-forward sequential cycles of 100 degrees from neutral position at a rate of 600 degrees /min) through a stepper-motor; working settings were defined via PC by an easy user-interface. Cell adhesion, morphology, cytoskeletal fiber orientation and gene expression of extracellular matrix proteins (collagen type I, tenascin C, collagen type III) were evaluated after three days of torsional stimulation in the bioreactor system. ?Results and Conclusions: The 3D bioreactor system was validated in terms of sterility, experimental reproducibility and flexibility. Cells adhered well onto the polymeric scaffolds. Collagen type I, tenascin C and collagen type III gene expression were significantly up-regulated when cells were cultured under torsion in the bioreactor for three days. In conclusion, we have developed a simple, efficient and versatile 3D cell-culture system to engineer ligament grafts. This system can be used either as a model to investigate mechanisms of tissue development or as a graft manufacturing system for possible clinical use in the field of regenerative medicine.

PMID: 20669141 [PubMed - in process]

 

An Adult Myometrial Pluripotential Precursor that Promotes Healing of Damaged Muscular Tissues.
July 30, 2010 at 10:34 AM

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An Adult Myometrial Pluripotential Precursor that Promotes Healing of Damaged Muscular Tissues.

In Vivo. 2010 Jul-Aug;24(4):431-41

Authors: Gálvez BG, Martín NS, Salama-Cohen P, Lazcano JJ, Coronado MJ, Lamelas ML, Alvarez-Barrientes A, Eiró N, Vizoso F, Rodríguez C

The use of adult stem cells for tissue and organ regeneration constitutes a promising alternative therapy in many human diseases that are currently not treatable. We have isolated a new cell type from mouse adult uterine biopsies (murine adult myometrial precursors or mAMPs) by means of using a simple and non-invasive approach. These cells have been characterized by surface markers, being positive for CD31, CD34, CD44, CD117, Stro-1 and Sca-1. A similar cell population (hAMPs) was isolated from human biopsies. AMPs can differentiate in vitro into a number of mesodermal (smooth and skeletal muscle, osteoblasts and adipocytes) as well as epidermal lineages (all neural lineages). AMPs are unusual adult stem cells as they still express some embryonic antigens and remain undifferentiated through a high number of passages before entering senescence. Importantly, when injected into animal models of muscular disease, AMPs can regenerate new muscle fibers, and promote functional muscular recovery. Moreover, these cells can regenerate the uterine lining after wound healing, reconstructing the uterine muscular architecture. In addition, these cells can form new vessels both in vitro and in vivo. We believe that these cells have superior features to other known adult stem cells and, consequently, their use holds great promise for regenerative medicine, drug development and basic research.

PMID: 20668309 [PubMed - in process]

 

The wnt signaling pathway as a potential target for therapies to enhance bone repair.
July 30, 2010 at 10:34 AM

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The wnt signaling pathway as a potential target for therapies to enhance bone repair.

Sci Transl Med. 2010 Jul 28;2(42):42ps36

Authors: Einhorn TA

The development of new technologies to enhance skeletal healing after fracture or surgery is an important goal of musculoskeletal regenerative medicine. Although the bone morphogenetic proteins have shown some efficacy in this area, there is a need for more effective and less expensive therapies for bone repair and regeneration. A recent report demonstrating that Wnt signaling could be used to stimulate bone healing may provide a new direction for designing anabolic therapies for the skeleton. The identification of human phenotypes demonstrating robust bone formation as a result of mutations in Wnt signaling provides a strong basis for pursuing this area of investigation.

PMID: 20668295 [PubMed - in process]

 

Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy.
July 30, 2010 at 10:34 AM

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Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy.

J Neurosci. 2010 Jul 28;30(30):9973-9983

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 - as supplied by publisher]

 

Defining Cell Identity by Comprehensive Gene Expression Profiling.
July 30, 2010 at 10:34 AM

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Defining Cell Identity by Comprehensive Gene Expression Profiling.

Curr Med Chem. 2010 Jul 29;

Authors: Toyoda M, Hamatani T, Okada H, Matsumoto K, Saito H, Umezawa A

The human body is composed of 60 trillion cells, which have their origin in a fertilized egg. During development, the potential of a cell or tissue can be achieved by environmental manipulation. Then, what molecular determinants underlie or accompany the potential of the cells? To obtain a broader understanding of these problems, it is important to analyze all transcripts / genes in a wide selection of cell types. The development of microarray technologies, which allow us to undertake parallel analyses of many genes, has led to a new era in medical science. In this review, we show that the global expression data have clearly elucidated discernible major trends of the phenomenon in preimplantation development and epithelial-mesenchymal transition, and of the character of marrow stromal cells, which are attracting a great deal of attention as they represent a valuable source of cells for regenerative medicine. One of the interesting results is obtained from microarray data of marrow stromal cells: OP9 cells that have been recognized as a type of niche-constituting preadipocyte derived from marrow stroma, are found to be chondroblasts. We also describe what effect each type of expression data would bring to reproductive and regenerative medicine, as well as offering an excellent model of cell differentiation in biology.

PMID: 20666720 [PubMed - as supplied by publisher]

 

Micro-Cavitary Hydrogel Mediating Phase Transfer Cell Culture for Cartilage Tissue Engineering.
July 30, 2010 at 10:34 AM

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Micro-Cavitary Hydrogel Mediating Phase Transfer Cell Culture for Cartilage Tissue Engineering.

Tissue Eng Part A. 2010 Jul 28;

Authors: Gong Y, Su K, Lau TT, Zhou R, Wang DA

Hydrogels have been widely used as cell-laden vehicles for therapeutic transplantation in regenerative medicine. Although the advantages of biocompatibility and injectability for in situ grafting have made hydrogel a superior candidate in tissue engineering, there remain challenges in long-term efficacy of tissue development using hydrogel, especially when more sophisticated applications are demanded. The major bottleneck lies in environmental constraints for neo-tissue generation in the gel bulk such as proliferation of encapsulated cells (colonies) per se and also accommodation of their endogenously produced extracellular matrices (ECMs). In this study, we endeavor to develop an innovative tissue engineering system to overcome these drawbacks through a novel micro-cavitary hydrogel (MCG)-based scaffolding technology and a novel phase transfer cell culture (PTCC) strategy to enable phenotypically bona fide neo-tissue formation in an injectable artificial graft. For this purpose, microspherical cavities are created in cell-encapsulating hydrogel bulk via a retarded dissolution of co-encapsulated gelatin microspheres. Based on proliferation and affinity selection, the encapsulated cell colonies adjacent to the gel/cavity interface will spontaneously outgrow the hydrogel phase and sprout into cavities, enabling neo-tissue islets to fill up the voids and further expand throughout the whole system for full tissue regeneration. The design of MCG-PTCC strategy was elicited from an observation of a spontaneous dynamic outgrowth of chondrocytes from the edge of a cell-laden hydrogel construct over prolonged cultivation - a phenomenon named "edge flourish" (EF). This MCG-PTCC strategy potentially introduce a new application to hydrogels in the field of regenerative medicine through elevation of its role as a cell vehicle to a 3D-transplantable growth-guiding platform for further development of newly generated tissues that better fulfill the demanding criteria of scaffolds in therapeutic tissue regeneration. Keywords: Biomaterials; Hydrogel; Tissue Engineering; Phase Transfer Cell Culture; Regenerative Medicine.

PMID: 20666616 [PubMed - as supplied by publisher]

 

Fluid Shear Stress Promotes an Endothelial-like Phenotype during the Early Differentiation of Embryonic Stem Cells.
July 30, 2010 at 10:34 AM

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Fluid Shear Stress Promotes an Endothelial-like Phenotype during the Early Differentiation of Embryonic Stem Cells.

Tissue Eng Part A. 2010 Jul 28;

Authors: Ahsan T, Nerem RM

Stem and progenitor cells are emerging as a potential source for cell-based therapies, in which large homogenous populations of differentiated cells are frequently deemed necessary for efficacy. Methods focused on biochemical cues have not yet yielded the numbers of endothelial cells thought necessary for cardiovascular applications. Interest in alternate methods has prompted the study of physical cues on stem and progenitor cell differentiation. In this study, fluid-based shear stress, at levels comparable to those experienced by endothelial cells in large vessels, was applied during the first few days of mouse embryonic stem cell differentiation. After two days of applied shear stress, there were increases in cell proliferation and in protein expression of endothelial markers (FLK1, VECAD, and PECAM). Furthermore, treatment increased the number of FLK1+ cells from 1% to 40%, which were then capable of forming vessel-like structures in vitro. Thus, shear stress may be used to direct differentiation of embryonic stem cells towards an endothelial-like phenotype, helping to address the cell sourcing issue in cardiovascular regenerative medicine and tissue engineering.

PMID: 20666609 [PubMed - as supplied by publisher]

 

Central role for Dab2 in mesenchymal stem cardiac protein expression and functional consequences after engraftment in acute myocardial infarction.
July 30, 2010 at 10:34 AM

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Central role for Dab2 in mesenchymal stem cardiac protein expression and functional consequences after engraftment in acute myocardial infarction.

Stem Cells Dev. 2010 Jul 28;

Authors: Mayorga ME, Dong F, Sundararaman S, Huang Y, Jiang Y, Howe PH, Penn MS

Adult mesenchymal stem cells (MSC) have been shown to spontaneously express cardiac proteins (CP) in vitro and to improve cardiac function after transplantation into experimentally induced acute myocardial infarction (AMI). However, if these effects are the result of MSC cardiac differentiation or a mere cooperative cellular interaction is a matter of active debate. Additionally, the molecular mechanisms involved in CP expression by adult stem cells in vitro and its possible benefit for cardiac regeneration and improved function remains unclear. Here we show that although MSC effectively engraft in AMI tissue, this engraftment leads to down-regulation of CP expression in the implanted MSC. We also found that pre-transplantation cardiac specification of MSC by exposure of the cells to TGFbeta1, led to sustained MSC CP expression without altering engraftment efficiency. This increase in CP expression was associated with greater improvement in cardiac function one and four weeks after AMI with TGFbeta1-pretreated MSC. We discovered that the TGFbeta1-enhanced cardiac potential of MSC was mediated by down-regulation of disabled-2 (Dab2) expression; suggesting an inverse correlation between Dab2 levels and CP expression/cardiac functional improvement following MSC engraftment. Our investigations further demonstrate that loss of Dab2 expression was sufficient to induce MSC CP expression and improve cardiac function following MSC engraftment after AMI. In summary, we define a novel role for the TGFbeta1 receptor adaptor protein Dab2 as a regulator of CP expression in MSC and its potential as a molecular target for the enhancement of stem cell cardiac specification for transplantation therapies.

PMID: 20666606 [PubMed - as supplied by publisher]

 

Macrophages as mediators of tumor immunosurveillance.
July 30, 2010 at 10:34 AM

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Macrophages as mediators of tumor immunosurveillance.

Trends Immunol. 2010 Jun;31(6):212-9

Authors: Jaiswal S, Chao MP, Majeti R, Weissman IL

Tumor immunosurveillance is a well-established mechanism for regulation of tumor growth. In this regard, most studies have focused on the role of T- and NK-cells as the critical immune effector cells. However, macrophages play a major role in the recognition and clearance of foreign, aged, and damaged cells. Macrophage phagocytosis is negatively regulated via the receptor SIRPalpha upon binding to CD47, a ubiquitously expressed protein. We recently showed that CD47 is up-regulated in myeloid leukemia and migrating hematopoietic progenitors, and that the level of protein expression correlates with the ability to evade phagocytosis. These results implicate macrophages in the immunosurveillance of hematopoietic cells and leukemias. The ability of macrophages to phagocytose tumor cells might be exploited therapeutically by blocking the CD47-SIRPalpha interaction.

PMID: 20452821 [PubMed - indexed for MEDLINE]

 

Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique.
July 30, 2010 at 10:34 AM

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Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique.

Am J Sports Med. 2010 May;38(5):943-9

Authors: Vasiliadis HS, Danielson B, Ljungberg M, McKeon B, Lindahl A, Peterson L

BACKGROUND: Various treatment options are available for articular cartilage lesions, but controversy exists regarding the quality of the repair tissue and the durability of the results posttreatment. Noninvasive techniques are needed for the assessment of the repair tissue. HYPOTHESIS: Magnetic resonance imaging (MRI) with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) can give valuable information regarding the quality and quantity of the repaired cartilage lesion. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Thirty-six knees in 31 patients were assessed 9 to 18 years after treatment with autologous chondrocyte implantation (ACI). All patients had isolated lesions. The knees were clinically evaluated with the Knee injury and Osteoarthritis Outcome Score and the dGEMRIC technique. The T1 value was measured for 2 regions of interest (ROIs), 1 in the repair tissue area (ROI 1) and 1 in the surrounding cartilage (ROI 2), giving information of the content of proteoglycans. RESULTS: The average T1 value in ROI 1 was 467.5 milliseconds and in ROI 2, 495.3 milliseconds, which yielded no significant difference, thus suggesting comparable levels of proteoglycans in the repair tissue and surrounding cartilage. Intralesional osteophytes were in 64% of the lesions, mainly in younger patients with osteochondritis dissecans lesions or a history of subchondral bone surgeries. Medium or large bone marrow edema was found in 14% of the knees and subchondral cysts, in 39%. There was no correlation between the KOOS and any MRI findings. CONCLUSION: Magnetic resonance imaging with dGEMRIC gives valuable information for the macroscopic appearance and micro-molecular quality of the repair tissue after ACI. Nine to 18 years posttreatment, the quality of the repair tissue is similar to the surrounding normal cartilage, although intralesional osteophytes, subchondral cysts, and bone marrow edema were common. The defect area is restored in most patients. However, there was no correlation between the dGEMRIC values and the KOOS outcomes.

PMID: 20185841 [PubMed - indexed for MEDLINE]

 

Erythropoietin receptor response circuits.
July 30, 2010 at 10:34 AM

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Erythropoietin receptor response circuits.

Curr Opin Hematol. 2010 May;17(3):169-76

Authors: Wojchowski DM, Sathyanarayana P, Dev A

PURPOSE OF REVIEW: In 1985-1989, erythropoietin (EPO), its receptor (EPOR), and janus kinase 2 were cloned; established to be essential for definitive erythropoiesis; and initially intensely studied. Recently, new impetus, tools, and model systems have emerged to re-examine EPO/EPOR actions, and are addressed in this review. Impetus includes indications that EPO affects significantly more than standard erythroblast survival pathways, the development of novel erythropoiesis-stimulating agents, increasing evidence for EPO/EPOR cytoprotection of ischemically injured tissues, and potential EPO-mediated worsening of tumorigenesis. RECENT FINDINGS: New findings are reviewed in four functional contexts: (pro)erythroblast survival mechanisms, new candidate EPO/EPOR effects on erythroid cell development and new EPOR responses, EPOR downmodulation and trafficking, and novel erythropoiesis-stimulating agents. SUMMARY: As Current Opinion, this monograph seeks to summarize, and provoke, new EPO/EPOR action concepts. Specific problems addressed include: beyond (and before) BCL-XL, what key survival factors are deployed in early-stage proerythroblasts? Are distinct EPO/EPOR signals transduced in stage-selective fashions? Is erythroblast proliferation also modulated by EPO/EPOR signals? What functions are subserved by new noncanonical EPO/EPOR response factors (e.g. podocalyxin like-1, tribbles 3, reactive oxygen species, and nuclear factor kappa B)? What key regulators mediate EPOR inhibition and trafficking? And for emerging erythropoiesis-stimulating agents, to what extent do activities parallel EPOs (or differ in advantageous, potentially complicating ways, or both)?

PMID: 20173635 [PubMed - indexed for MEDLINE]

 

Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: report of two initial cases.
July 30, 2010 at 10:34 AM

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Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: report of two initial cases.

Int J Urol. 2010 Jan;17(1):75-82

Authors: Yamamoto T, Gotoh M, Hattori R, Toriyama K, Kamei Y, Iwaguro H, Matsukawa Y, Funahashi Y

OBJECTIVES: To report a novel cell therapy using autologous adipose tissue-derived stem cells (ADSC) for stress urinary incontinence caused by urethral sphincteric deficiency and the outcomes in two initial cases undergoing periurethral injection of stem cells for the treatment of urinary incontinence after radical prostatectomy. METHODS: Two patients with moderate stress incontinence after radical prostatectomy were enrolled. After liposuction of 250 mL of adipose tissue from the abdomen, we isolated ADSC from this tissue by using the Celution system. Subsequently, the isolated ADSC and a mixture of stem cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short-term outcomes during a 12-week follow-up were assessed by a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography, and magnetic resonance imaging. RESULTS: Urinary incontinence progressively improved after 2 weeks of injection up to 12 weeks in terms of decreased leakage volume in a 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life as per the questionnaire. In urethral pressure profile, both maximum urethral closing pressure and functional profile length increased. Ultrasonography and magnetic resonance imaging showed sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri- and postoperatively. CONCLUSION: This preliminary study showed that periurethral injection of the autologous ADSC is a safe and feasible treatment modality for stress urinary incontinence.

PMID: 20002225 [PubMed - indexed for MEDLINE]

 

The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study.
July 30, 2010 at 4:45 AM

The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study.

Magn Reson Med. 2010 Aug;64(2):341-8

Authors: Cheng HL, Loai Y, Beaumont M, Farhat WA

Bladder acellular matrices (ACMs) derived from natural tissue are gaining increasing attention for their role in tissue engineering and regeneration. Unlike conventional scaffolds based on biodegradable polymers or gels, ACMs possess native biomechanical and many acquired biologic properties. Efforts to optimize ACM-based scaffolds are ongoing and would be greatly assisted by a noninvasive means to characterize scaffold properties and monitor interaction with cells. MRI is well suited to this role, but research with MRI for scaffold characterization has been limited. This study presents initial results from quantitative MRI measurements for bladder ACM characterization and investigates the effects of incorporating hyaluronic acid, a natural biomaterial useful in tissue-engineering and regeneration. Measured MR relaxation times (T(1), T(2)) and diffusion coefficient were consistent with increased water uptake and glycosaminoglycan content observed on biochemistry in hyaluronic acid ACMs. Multicomponent MRI provided greater specificity, with diffusion data showing an acellular environment and T(2) components distinguishing the separate effects of increased glycosaminoglycans and hydration. These results suggest that quantitative MRI may provide useful information on matrix composition and structure, which is valuable in guiding further development using bladder ACMs for organ regeneration and in strategies involving the use of hyaluronic acid. Magn Reson Med, 2010. (c) 2010 Wiley-Liss, Inc.

PMID: 20665777 [PubMed - in process]

 

Hydroxyapatite/polyurethane scaffold incorporated with drug-loaded ethyl cellulose microspheres for bone regeneration.
July 30, 2010 at 4:45 AM

Hydroxyapatite/polyurethane scaffold incorporated with drug-loaded ethyl cellulose microspheres for bone regeneration.

J Biomed Mater Res B Appl Biomater. 2010 Jul 27;

Authors: Liu H, Zhang L, Shi P, Zou Q, Zuo Y, Li Y

The purpose of this study is to explore and develop biodegradable scaffold for bone regeneration or tissue engineering with the capacity of controlled drug delivery. Ceftazidime as a model drug was encapsulated in ethyl cellulose (EC) microspheres, which were subsequently incorporated in a hydroxyapatite/polyurethane (HA/PU) composite scaffold to generate an antibiotic drug delivery system. HA/PU scaffolds had an interconnected pore network with an average porosity of about 83%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy. The drug-loaded EC microspheres were uniformly distributed in the HA/PU scaffold matrix and showed no significant effect on the pore structure of the scaffold. Incorporation of microspheres into scaffolds significantly reduced the initial burst release, and the system exhibited a sustained release of the model drug for up to 60 days. Moreover, the scaffold with drug-loaded microspheres was proved to be an effective drug delivery system with good cytocompatibility and antibacterial properties. The novel drug-loaded microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery in bone regeneration or bone tissue engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.

PMID: 20665683 [PubMed - as supplied by publisher]

 

PLGA nanofiber-coated silk microfibrous scaffold for connective tissue engineering.
July 30, 2010 at 4:45 AM

PLGA nanofiber-coated silk microfibrous scaffold for connective tissue engineering.

J Biomed Mater Res B Appl Biomater. 2010 Jul 27;

Authors: Sahoo S, Lok Toh S, Hong Goh JC

A modified degumming technique, involving boiling in 0.25% Na(2)CO(3) with addition of 1% sodium dodecyl sulphate and intermittent ultrasonic agitation, was developed for knitted silk scaffolds. Sericin was efficiently removed, while mechanical and structural properties of native silk fibroin were preserved. Biocompatible and mechanically robust hybrid nano-microscaffolds were fabricated by coating these degummed silk scaffolds with an intervening adhesive layer of silk solution followed by electrospun poly-lactic-co-glycolic acid (PLGA) nanofibers. Cell proliferation on the hybrid silk scaffolds was improved by seeding cells on both surfaces of the flat scaffolds. Rolling up and continued culture of the cell-seeded hybrid scaffolds yielded cylindrical constructs that permitted cell proliferation, extracellular matrix deposition, and generated ligament/tendon graft analogs. Although PLGA-based hybrid scaffolds have earlier been proposed for dense connective tissue engineering, rapid biodegradation of PLGA was a drawback. In contrast, the underlying strong and slowly-degrading microfibrous silk scaffold used in this study ensured that the hybrid scaffold maintained adequate mechanical properties for longer periods, which is vital for continued support to the injured ligament/tendon throughout its healing period. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.

PMID: 20665681 [PubMed - as supplied by publisher]

 

Apoptosis of mesenchymal stem cells induced by hydrogen peroxide concerns both endoplasmic reticulum stress and mitochondrial death pathway through regulation of caspases, p38 and JNK.
July 30, 2010 at 4:45 AM

Apoptosis of mesenchymal stem cells induced by hydrogen peroxide concerns both endoplasmic reticulum stress and mitochondrial death pathway through regulation of caspases, p38 and JNK.

J Cell Biochem. 2010 Jul 27;

Authors: Wei H, Li Z, Hu S, Chen X, Cong X

Poor survival of mesenchymal stem cells (MSCs) compromised the efficacy of stem cell therapy for myocardial infarction. The increase of exogenous reactive oxygen species (ROS) in infracted heart is one of the important factors that challenged the survival of donor MSCs. In the study we aimed to evaluate the effect of oxidative stress on the cell death of MSCs and investigate its mechanisms in order to help with the identification of new biological compounds to reduce donor cells damage. Apoptosis of MSCs were evaluated with Hoechst33342 staining and flow cytometry analysis. The mitochondrial membrane potential of MSCs was analyzed with JC-1 staining. Signaling pathways involved in H(2)O(2) induced apoptosis were analyzed with western blot. H(2)O(2) induced apoptosis of MSCs in a dose and time dependent manner. H(2)O(2) induced apoptosis of MSCs via both endoplasmic reticulum (ER) and mitochondrial pathways rather than extrinsic apoptosis pathway. H(2)O(2) caused transient rather than sustained activation of p38 and JNK with no effect on ERK1/2 pathway. P38 was involved in the regulation of early apoptosis of MSCs while JNK was involved in the late apoptosis. P38 directed both ER stress and mitochondria death pathway in the early apoptosis. In conclusion, Exogenous ROS was a major factor to induce apoptosis of MSCs. Both ER stress and mitochondria death pathway were involved in the apoptosis of MSCs. H(2)O(2) activated p38 that directed the above two pathways in the regulation of early apoptosis of MSCs while JNK was involved in the late apoptosis of MSCs. J. Cell. Physiol. (c) 2010 Wiley-Liss, Inc.

PMID: 20665666 [PubMed - as supplied by publisher]

 

Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes.
July 30, 2010 at 4:45 AM

Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes.

J Cell Biochem. 2010 Jul 21;

Authors: Arufe MC, Fuente AD, Fuentes I, de Toro FJ, Blanco FJ

In this study we analyzed the chondrogenic potential of subpopulations of MSCs derived from human synovial membranes enriched for CD73, CD106 and CD271 markers.Subpopulations of human synovial membrane MSCs enriched for CD73, CD106 and CD271 markers were isolated using a cytometry sorter and characterized by flow cytometry for MSC markers. The expression of Sox9, Nanog and Runx2 genes by these cells was measured by reverse transcriptase-polymerase chain reaction. The chondrogenesis of each subpopulation was assessed by culturing the cells in a defined medium to produce spontaneous spheroid formation and differentiation towards chondrocyte-like cells. The examination of the spheroids by histological and immunohistochemical analyses for collagen type II (COL2), aggrecan, collagen type I (COL1), metalloprotease 13 (MMP13) and collagen type X (COLX) levels were performed to assess their chondrogenesis capacity. The adipogenesis and osteogenesis potential of each subpopulation was determined using commercial media; the resulting cells were stained with oil red O or red alizarin to test the degree of differentiation.The subpopulations had different profiles of cells positive for the MSC markers CD44, CD69, CD73, CD90 and CD105 and showed different expression levels of the genes Sox9, Nanog, Runx2 involved in chondrogenesis, undifferentiation and osteoblastogenesis, respectively. Immunohistochemical analysis demonstrated that COL1, COL2, COLX, MMP13 and aggrecan were expressed in the spheroids as soon as 14 days of culture. The CD271(+) subpopulation expressed the highest levels of COL2 staining compared to the other subpopulations. CD105 and Runx2 were shown by immunohistochemistry and genetic analysis to have significantly higher expression CD271+ subpopulation than the other subpopulations.Spheroids formed from CD271-enriched and CD73-enriched MSCs from normal human synovial membranes mimic the native cartilage extracellular matrix more closely than CD106(+) MSCs and are possible candidates for use in cartilage tissue engineering. Both cell types have potential for promoting the differentiation of MSCs into chondrocytes, presenting new possibilities for achieving intrinsic cartilage repair. (c) 2010 Wiley-Liss, Inc.

PMID: 20665538 [PubMed - as supplied by publisher]

 

Guest Editorial: Regenerative rehabilitation: A call to action.
July 30, 2010 at 4:45 AM

Guest Editorial: Regenerative rehabilitation: A call to action.

J Rehabil Res Dev. 2010;47(3):xi-xvi

Authors: Ambrosio F, Russell A

PMID: 20665343 [PubMed - in process]

 

Modification of the chiral selectivity of d-glucose oxidase and l-lactate oxidase in a collagen matrix.
July 30, 2010 at 4:45 AM

Modification of the chiral selectivity of d-glucose oxidase and l-lactate oxidase in a collagen matrix.

Phys Chem Chem Phys. 2010 Jul 22;

Authors: Kataky R, Zawawi RM

A chiral, biocompatible, conducting material comprising collagen I, silica gel and ferrocene was found to modify and invert, the chiral selectivity of d-glucose oxidase and l-lactate oxidase. This result may have implications as collagen matrices are widely used in drug delivery, biosensing and tissue engineering. Investigations were carried out using electrochemical methods, FTIR spectroscopy and circular dichroism.

PMID: 20664851 [PubMed - as supplied by publisher]

 

Stimuli-responsive microwells for formation and retrieval of cell aggregates.
July 30, 2010 at 4:45 AM

Stimuli-responsive microwells for formation and retrieval of cell aggregates.

Lab Chip. 2010 Jul 27;

Authors: Tekin H, Anaya M, Brigham MD, Nauman C, Langer R, Khademhosseini A

Generating cell aggregates is beneficial for various applications ranging from biotechnology to regenerative therapies. Previously, poly(ethylene glycol) (PEG) microwells have been demonstrated as a potentially useful method for generating controlled-size cell aggregates. In addition to controlling cell aggregate size and homogeneity, the ability to confine cell aggregates on glass adhesive substrates and subsequently retrieve aggregates from microwells for further experimentation and analysis could be beneficial for various applications. However, it is often difficult to retrieve cell aggregates from these microwells without the use of digestive enzymes. This study describes the stable formation of cell aggregates in responsive microwells with adhesive substrates and their further retrieval in a temperature dependent manner by exploiting the stimuli responsiveness of these microwells. The responsive polymer structure of the arrays can be used to thermally regulate the microwell diameters causing a mechanical force on the aggregates, subsequently facilitating the retrieval of cell aggregates from the microwells with high efficiency compared to PEG arrays. This approach can be potentially integrated into high-throughput systems and may become a versatile tool for various applications that require aggregate formation and experimentation, such as tissue engineering, drug discovery, and stem cell biology.

PMID: 20664846 [PubMed - as supplied by publisher]

 

Modulation of rabbit corneal epithelial cells fate using embryonic stem cell extract.
July 30, 2010 at 4:45 AM

Modulation of rabbit corneal epithelial cells fate using embryonic stem cell extract.

Mol Vis. 2010;16:1154-61

Authors: Zhan W, Liu Z, Liu Y, Ke Q, Ding Y, Lu X, Wang Z

PURPOSE: To develop a new culture system to cultivate differentiated autologous cells in vitro for cell therapy and tissue engineering. METHODS: After incubation in murine embryonic stem cell (ESC) extract for 1 h, streptolysin-O (SLO) permeabilized cells were resealed with CaCl(2) and continually cultured for weeks. The morphological study was analyzed by light microscopy. Isolated colonies were selected and expanded to establish cell lines. Octamer-4 (Oct-4), stage-specific embryonic antigen-1 (SSEA-1), transformation-related protein 63 (p63), ATP-binding cassette subfamily G, member 2 (ABCG2), and cytokeratin3 (K3) were detected by indirect immunofluorescent staining. Oct-4, K3, and p63 were also detected by RT-PCR analysis. To examine the stemness characteristics of the induced cells, both alkaline phosphatase (AKP) staining and tumorigenicity detection were performed, respectively. RESULTS: Reprogramming was induced in corneal epithelial cells. The reprogrammed cells showed characteristics similar to ESCs in the early weeks, including colony formation, positive AKP staining, and multi-potential differentiation in vivo. Oct-4 and SSEA1 protein expression was upregulated. However, these changes were not persistent or stable. With the passage of time, the colonies became flat. The ESC markers were downregulated, while epithelial cell related proteins gradually increased. CONCLUSIONS: Less terminal differentiated rabbit corneal epithelial cells could be induced to a more pluripotent state with embryonic stem cell extract (ESC-E). These cells have the potential to return to the beginning of their own lineage and obtain the ability of long-term growth. Our fi ndings indicate that this culture system can generate low-immunogenic autologous cells for use in regenerative medicine.

PMID: 20664691 [PubMed - in process]

 

Cellular Antioxidant Levels Influence Muscle Stem Cell Therapy.
July 30, 2010 at 4:45 AM

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Cellular Antioxidant Levels Influence Muscle Stem Cell Therapy.

Mol Ther. 2010 Jul 27;

Authors: Drowley L, Okada M, Beckman S, Vella J, Keller B, Tobita K, Huard J

Although cellular transplantation has been shown to promote improvements in cardiac function following injury, poor cell survival following transplantation continues to limit the efficacy of this therapy. We have previously observed that transplantation of muscle-derived stem cells (MDSCs) improves cardiac function in an acute murine model of myocardial infarction to a greater extent than myoblasts. This improved regenerative capacity of MDSCs is linked to their increased level of antioxidants such as glutathione (GSH) and superoxide dismutase. In the current study, we demonstrated the pivotal role of antioxidant levels on MDSCs survival and cardiac functional recovery by either reducing the antioxidant levels with diethyl maleate or increasing antioxidant levels with N-acetylcysteine (NAC). Both the anti- and pro-oxidant treatments dramatically influenced the survival of the MDSCs in vitro. When NAC-treated MDSCs were transplanted into infarcted myocardium, we observed significantly improved cardiac function, decreased scar tissue formation, and increased numbers of CD31(+) endothelial cell structures, compared to the injection of untreated and diethyl maleate-treated cells. These results indicate that elevating the levels of antioxidants in MDSCs with NAC can significantly influence their tissue regeneration capacity.

PMID: 20664528 [PubMed - as supplied by publisher]

 

Regulatory mechanisms in vascular calcification.
July 30, 2010 at 4:45 AM

Regulatory mechanisms in vascular calcification.

Nat Rev Cardiol. 2010 Jul 27;

Authors: Sage AP, Tintut Y, Demer LL

In the past decade, the prevalence, significance, and regulatory mechanisms of vascular calcification have gained increasing recognition. Over a century ago, pathologists recognized atherosclerotic calcification as a form of extraskeletal ossification. Studies are now identifying the mechanism of this remarkable process as a recapitulation of embryonic endochondral and membranous ossification through phenotypic plasticity of vascular cells that function as adult mesenchymal stem cells. These embryonic developmental programs, involving bone morphogenetic proteins and potent osteochondrogenic transcription factors, are triggered and modulated by a variety of inflammatory, metabolic, and genetic disorders, particularly hyperlipidemia, chronic kidney disease, diabetes, hyperparathyroidism, and osteoporosis. They are also triggered by loss of powerful inhibitors, such as fetuin A, matrix Gla protein, and pyrophosphate, which ordinarily restrict biomineralization to skeletal bone. Teleologically, soft-tissue calcification might serve to create a wall of bone to sequester noxious foci such as chronic infections, parasites, and foreign bodies. This Review focuses on atherosclerotic and medial calcification. The capacity of the vasculature to produce mineral in culture and to produce de novo, vascularized, trabecular bone and cartilage tissue, even in patients with osteoporosis, should intrigue investigators in tissue engineering and regenerative biology.

PMID: 20664518 [PubMed - as supplied by publisher]

 

Modified Gellan Gum hydrogels with tunable physical and mechanical properties.
July 30, 2010 at 4:45 AM

Modified Gellan Gum hydrogels with tunable physical and mechanical properties.

Biomaterials. 2010 Jul 19;

Authors: Coutinho DF, Sant SV, Shin H, Oliveira JT, Gomes ME, Neves NM, Khademhosseini A, Reis RL

Gellan Gum (GG) has been recently proposed for tissue engineering applications. GG hydrogels are produced by physical crosslinking methods induced by temperature variation or by the presence of divalent cations. However, physical crosslinking methods may yield hydrogels that become weaker in physiological conditions due to the exchange of divalent cations by monovalent ones. Hence, this work presents a new class of GG hydrogels crosslinkable by both physical and chemical mechanisms. Methacrylate groups were incorporated in the GG chain, leading to the production of a methacrylated Gellan Gum (MeGG) hydrogel with highly tunable physical and mechanical properties. The chemical modification was confirmed by proton nuclear magnetic resonance ((1)H NMR) and Fourier transform infrared spectroscopy (FTIR-ATR). The mechanical properties of the developed hydrogel networks, with Young's modulus values between 0.15 and 148 kPa, showed to be tuned by the different crosslinking mechanisms used. The in vitro swelling kinetics and hydrolytic degradation rate were dependent on the crosslinking mechanisms used to form the hydrogels. Three-dimensional (3D) encapsulation of NIH-3T3 fibroblast cells in MeGG networks demonstrated in vitro biocompatibility confirmed by high cell survival. Given the highly tunable mechanical and degradation properties of MeGG, it may be applicable for a wide range of tissue engineering approaches.

PMID: 20663552 [PubMed - as supplied by publisher]

 

X-Ray Imaging of Poly(Ethylene Glycol) Hydrogels Without Contrast Agents.
July 30, 2010 at 4:45 AM

X-Ray Imaging of Poly(Ethylene Glycol) Hydrogels Without Contrast Agents.

Tissue Eng Part C Methods. 2010 Jul 27;

Authors: Brey EM, Appel A, Chiu YC, Zhong Z, Cheng MH, Engel H, Anastasio MA

Hydrogels have shown promise for a number of tissue engineering applications. However, their high water content results in little or no image contrast when using conventional X-ray imaging techniques. X-ray imaging techniques based on phase-contrast have shown promise for biomedical application due to their ability to provide information about the X-ray refraction properties of samples. Nonporous and porous poly(ethylene glycol) hydrogels were synthesized and imaged using a synchrotron light source employing a silicon analyzer crystal and an X-ray energy of 40-keV. Data were acquired at 21 angular analyzer positions spanning the range of -5 to 5 murad. Images that depict the projected X-ray absorption, refraction, and ultra-small-angle scatter (USAXS) properties of the hydrogels were reconstructed from the measurement data. The poly(ethylene glycol) hydrogels could be discerned from surrounding water and soft tissue in the refraction image but not the absorption or USAXS images. In addition, the refraction images of the porous hydrogels have a speckle pattern resulting in increased image texture in comparison to nonporous hydrogels. To our knowledge, this is the first study to show that X-ray phase-contrast imaging techniques can identify and provide detail on hydrogel structure without the addition of contrast agents.

PMID: 20662738 [PubMed - as supplied by publisher]

 

Comparative study of stemness characteristics of mesenchymal cells from bone marrow of children and adults.
July 30, 2010 at 4:45 AM

Comparative study of stemness characteristics of mesenchymal cells from bone marrow of children and adults.

Cytotherapy. 2010 Jul 22;

Authors: Choumerianou DM, Martimianaki G, Stiakaki E, Kalmanti L, Kalmanti M, Dimitriou H

Abstract Background aims. Age-related changes that could affect the biologic features of mesenchymal stromal cells (MSC), such as a decrease in proliferation and osteoblast differentiation capacity and an increase of senescence markers and apoptosis, have been reported recently. The aim of this study was the evaluation of age-related characteristics and the correlation of age with the functional properties of MSC. Methods. The doubling time (DT), colony-forming unit-fibroblast (CFU-F) colonies and surface antigen expression of MSC isolated from bone marrow (BM) of children (C-MSC) were compared with those from adults (A-MSC). The expression of Oct-4 and Nanog transcripts and the relative telomere length were evaluated in both groups. Results. DT values were lower in C-MSC compared with A-MSC, and a higher CFU-F count was observed in children. However, the expression of Oct-4 and Nanog did not differ between C-MSC and A-MSC and was not correlated with the proliferative capacity. The telomere length was significantly higher in C-MSC compared with A-MSC. Conclusions. These data suggest that children's BM-derived MSC could be a more advantageous source of these cells for tissue engineering and cell therapy.

PMID: 20662612 [PubMed - as supplied by publisher]

 

Growth factor and cytokine expression of human mesenchymal stromal cells is not altered in an in vitro model of tissue damage.
July 30, 2010 at 4:45 AM

Growth factor and cytokine expression of human mesenchymal stromal cells is not altered in an in vitro model of tissue damage.

Cytotherapy. 2010 Jul 22;

Authors: Montzka K, Führmann T, Müller-Ehmsen J, Wöltje M, Brook GA

Abstract Background aims. The beneficial effect of human (h) mesenchymal stromal cell (MSC) transplantation in a variety of cell-based intervention strategies is widely believed to be because of paracrine mechanisms. The modification of hMSC cytokine and growth-factor expression patterns were studied following exposure to lipopolysaccharide (LPS) and tissue homogenates (representing tissue debris) from normal and pathologic tissues. Methods. Human bone marrow-derived MSC were stimulated with LPS or exposed to homogenate from normal or pathologic rat spinal cord or heart. The expression profiles of a number of cytokines and growth factors were investigated using quantitative reverse transcription (RT)-polymerase chain reaction (PCR) with human-specific primers. The effects of tissue homogenates on hMSC proliferation and migratory behavior were also investigated. Results. Stimulation of hMSC with LPS resulted in an up-regulation of interleukin (IL)-1beta, IL-6 and IL-8. However, the pattern of up-regulation varied between donor samples. Furthermore, LPS treatment resulted in a donor-dependent alteration of growth factor expression. Induction of a shift in expression pattern was not observed following exposure to homogenates from either normal or pathologic tissues. Tissue homogenates did stimulate cell proliferation, but not migration. Conclusions. The hMSC expression pattern is apparently stable, even when cells are confronted by debris from different tissue types. However, treatment of hMSC with LPS is able to change the expression of cytokines and growth factors in a donor-dependent manner that may enhance their potential use in regenerative medicine.

PMID: 20662610 [PubMed - as supplied by publisher]

 

Impaired bladder function in aging male rats.
July 30, 2010 at 4:45 AM

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Impaired bladder function in aging male rats.

J Urol. 2010 Jul;184(1):378-85

Authors: Zhao W, Aboushwareb T, Turner C, Mathis C, Bennett C, Sonntag WE, Andersson KE, Christ G

PURPOSE: The prevalence of bladder dysfunctions increases with age. In humans it is difficult to separate changes related to exogenous factors from those directly related to the aging process. Some confounding variables can be avoided by studying age related changes in an animal model. We evaluated the impact of age on bladder function in vivo and in vitro, and characterized the corresponding morphological changes. MATERIALS AND METHODS: Young (4 to 6 months old) and old (older than 28 to 30 months) male Fischer/Brown Norway rats were used in the study. Cystometric studies were done in conscious, freely moving rats. After cystometry tissue strips from the bladder body were used in in vitro studies of muscarinic receptor activation and electrical field stimulation, and histological examination. RESULTS: Old rats had higher bladder weight than young rats but the bladder-to-body weight ratio did not change. We noted significant age related differences in 8 of 10 cystometric parameters. Old rats had increased bladder capacity, post-void residual volume, micturition volume and frequency, baseline and intermicturition pressure, and spontaneous activity but decreased micturition pressure. Bladder strip responses to carbachol and electrical field stimulation were significantly lower in old than in young rats. Histological examination revealed urothelial thinning, lower muscle mass and higher collagen content in the bladders of old vs young rats. CONCLUSIONS: Physiological aging alters bladder function in male rats even when external factors remain constant. Thus, in old rats bladder capacity, post-void residual urine and spontaneous activity are higher, and responses to muscarinic receptor stimulation and electrical field stimulation are lower than in young rats. Such changes correspond to findings in aging human bladders, supporting the view that the Fischer/Brown Norway rat is a useful model in which to study age related bladder function changes.

PMID: 20488483 [PubMed - indexed for MEDLINE]

 

A novel biomimetic composite scaffold hybridized with mesenchymal stem cells in repair of rat bone defects models.
July 29, 2010 at 11:45 PM

A novel biomimetic composite scaffold hybridized with mesenchymal stem cells in repair of rat bone defects models.

J Biomed Mater Res A. 2010 Jul 27;

Authors: Xu C, Su P, Wang Y, Chen X, Meng Y, Liu C, Yu X, Yang X, Yu W, Zhang X, Xiang AP

In this study, the in vivo bone-regenerative potential of a novel bioactive glass-collagen-hyaluronic acid-Phosphatidylserine (BG-COL-HYA-PS) composite scaffold hybridized with mesenchymal stem cells (MSCs) was investigated in a rat bone defect model. HrGFP-labeled MSCs were cultured for 2 weeks on the BG-COL-HYA-PS scaffold before implantation into the defect. A cell-free scaffold and an untreated defect were used as controls. The regeneration process was evaluated by histology, X-ray, and mechanical rigidity experiments at different time points post-implantation. The results revealed that BG-COL-HYA-PS scaffold exhibited a low inflammatory response and foreign body response within 3 weeks. At week 6, those responses disappeared following the resorption of scaffolds and the formation of new bone. Compared with the pure scaffold or empty group, the introduction of MSCs into the porous scaffold dramatically enhanced the efficiency of the new bone formation and biomechanical property of the femur. In addition, the transplanted MSCs could survive for up to 3 weeks or longer. The results demonstrated that the BG-COL-HYA-PS scaffold was biocompatible and osteoconductive and the transplanted MSCs with the scaffold enhanced the healing of the bone defect. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

PMID: 20665678 [PubMed - as supplied by publisher]

 

A cloned pig model for examining atherosclerosis induced by high fat, high cholesterol diets.
July 29, 2010 at 11:45 PM

A cloned pig model for examining atherosclerosis induced by high fat, high cholesterol diets.

Anim Biotechnol. 2010 Jul;21(3):179-87

Authors: Jensen TW, Mazur MJ, Pettigew JE, Perez-Mendoza VG, Zachary J, Schook LB

The pig is a recognized model for the onset of coronary heart disease and heart attacks. Previous studies have shown that serum cholesterol levels in the pig can be elevated using a high fat, high cholesterol (HFHC) diet. What has been lacking is a genetically defined model corresponding to human ApoE4 susceptibility that can be linked to diets capable of inducing atherosclerosis. This study used a cloned pig model to examine the impact of cholesterol levels with the development of aorta fatty deposits leading to atherosclerosis. Diets were formulated using vegetable sources of protein to provide similar intakes of metabolizable energy, calcium, phosphorous and principal amino acids in both control and HFHC groups. After 60 days, the HFHC group demonstrated a 40-fold increase in aortic fatty streak lesion area combined with 6- and 11-fold increases in total and LDL cholesterol, respectively, over control diet fed cloned pigs. Previous studies have suffered from either imbalanced total caloric intake, an overall imbalance in the nutrition of the control versus HFHC groups or genetic heterogeneity when evaluating dietary constraints related to atherosclerosis. This study demonstrated that cloned, genetically-defined ApoE4 pigs provided balanced nutrition diets provide an experimental system ideally suited to examining atherosclerosis and the onset of coronary heart disease.

PMID: 20665290 [PubMed - in process]

 

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