| New strategy for mending broken hearts?
October 10, 2009 at 6:08 pm
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| Self-Renewal of the Long-Term Reconstituting Subset of Hematopoietic Stem Cells is Regulated by Ikaros.
October 10, 2009 at 7:06 am
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| | Self-Renewal of the Long-Term Reconstituting Subset of Hematopoietic Stem Cells is Regulated by Ikaros. Stem Cells. 2009 Oct 8; Authors: Papathanasiou P, Attema JL, Karsunky H, Hosen N, Sontani Y, Hoyne GF, Tunningley R, Smale ST, Weissman IL Hematopoietic stem cells (HSCs) are rare, ancestral cells that underlie the development, homeostasis, aging, and regeneration of the blood. Here we show the chromatin-associated protein Ikaros is a crucial self-renewal regulator of the long-term (LT) reconstituting subset of HSCs. Ikaros, and associated family member proteins, are highly expressed in self-renewing populations of stem cells. Ikaros point mutant mice initially develop LT-HSCs with the surface phenotype cKit+Thy1.1(lo)Lin(-/lo)Sca1+Flk2-CD150+ during fetal ontogeny but are unable to maintain this pool, rapidly losing it within two days of embryonic development. A synchronous loss of megakaryocyte/erythrocyte progenitors results, along with a fatal, fetal anemia. At this time, mutation of Ikaros exerts a differentiation defect upon common lymphoid progenitors which cannot be rescued with an ectopic Notch signal in vitro, with hematopoietic cells preferentially committing to the NK lineage. Whilst dispensable for the initial embryonic development of blood, Ikaros is clearly needed for maintenance of this tissue. Achieving successful clinical tissue regeneration necessitates understanding degeneration, and these data provide a striking example by a discrete genetic lesion in the cells underpinning tissue integrity during a pivotal timeframe of organogenesis. PMID: 19816952 [PubMed - as supplied by publisher] |
| Klf4 Directly Interacts with Oct4 and Sox2 to Promote Reprogramming.
October 10, 2009 at 7:06 am
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| | Klf4 Directly Interacts with Oct4 and Sox2 to Promote Reprogramming. Stem Cells. 2009 Oct 8; Authors: Wei Z, Yang Y, Zhang P, Andrianakos R, Hasegawa K, Lyu J, Chen X, Bai G, Liu C, Pera M, Lu W Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by ectopic expression of specific sets of transcription factors. Oct4, Sox2, and Klf4, factors that share many target genes in embryonic stem (ES) cells, are critical components in various reprogramming protocols. Nevertheless, it remains unclear whether these factors function together or separately in reprogramming. Here we show that Klf4 interacts directly with Oct4 and Sox2 when expressed at levels sufficient to induce iPS cells. Endogenous Klf4 also interacts with Oct4 and Sox2 in iPS cells and in mouse ES cells. The Klf4 C-terminus, which contains three tandem zinc fingers, is critical for this interaction and is required for activation of the target gene Nanog. In addition, Klf4 and Oct4 co-occupy the Nanog promoter. A dominant negative mutant of Klf4 can compete with wild-type Klf4 to form defective Oct4/Sox2/Klf4 complexes and strongly inhibit reprogramming. In the absence of Klf4 overexpression, interaction of endogenous Klf4 with Oct4/Sox2 is also required for reprogramming. This study supports the idea that direct interactions between Klf4, Oct4 and Sox2 are critical for somatic cell reprogramming. PMID: 19816951 [PubMed - as supplied by publisher] |
| Calcium Aluminate, RGD-Modified Calcium Aluminate, and beta-Tricalcium Phosphate Implants in a Calvarial Defect.
October 10, 2009 at 7:06 am
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| | Calcium Aluminate, RGD-Modified Calcium Aluminate, and beta-Tricalcium Phosphate Implants in a Calvarial Defect. J Craniofac Surg. 2009 Sep;20(5):1538-43 Authors: Miljkovic ND, Cooper GM, Hott SL, Disalle BF, Gawalt ES, Smith DM, McGowan K, Marra KG Calcium aluminate (CaAl), arginine-glycine-aspartic acid-modified CaAl, and beta-tricalcium phosphate (TCP) implants were studied in a rat calvarial critical-sized defect model. The rates of newly formed bone and osteointegration were measured using 3 different methods: radiography, micro-computed tomography, and histologic examination. After 4 weeks, there was no new bone formed and no signs of osteointegration into the skull bone in the CaAl or arginine-glycine-aspartic acid-modified CaAl groups, and thick fibrous capsules were visible around the whole circumference of the implants in both groups. In the beta-TCP group, neovascularization of the implant was observed, which is consistent with the early phase of new bone formation. In addition, in the beta-TCP group, signs of implant integration into the host tissue were evident at 4 weeks. There was no soft tissue reaction around the beta-TCP implant. These observations suggest that more specific adhesion peptides may be needed to activate the bioinert CaAl implant and promote bone formation in the craniofacial skeleton. PMID: 19816293 [PubMed - in process] |
| Bone tissue engineering scaffolds of today and tomorrow.
October 10, 2009 at 7:06 am
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| | Bone tissue engineering scaffolds of today and tomorrow. J Craniofac Surg. 2009 Sep;20(5):1531-2 Authors: Panetta NJ, Gupta DM, Longaker MT PMID: 19816291 [PubMed - in process] |
| Self-Assembling Peptide Nanofiber Scaffolds, Platelet-Rich Plasma, and Mesenchymal Stem Cells for Injectable Bone Regeneration With Tissue Engineering.
October 10, 2009 at 7:06 am
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| | Self-Assembling Peptide Nanofiber Scaffolds, Platelet-Rich Plasma, and Mesenchymal Stem Cells for Injectable Bone Regeneration With Tissue Engineering. J Craniofac Surg. 2009 Sep;20(5):1523-1530 Authors: Yoshimi R, Yamada Y, Ito K, Nakamura S, Abe A, Nagasaka T, Okabe K, Kohgo T, Baba S, Ueda M The purpose of this study was to investigate a capability of PuraMatrix (PM), which is a self-assembling peptide nanomaterial, as a scaffold for bone regeneration in combination with dog mesenchymal stem cells (dMSCs) and/or platelet-rich plasma (PRP) using tissue engineering and regenerative technology. Initially, teeth were extracted from an adult hybrid dog's mandible region. After 4 weeks, bone defects were prepared on both sides of the mandible with a trephine bar. The following graft materials were implanted into these defects: (1) control (defect only), (2) PM, (3) PM/PRP, (4) PM/dMSCs, and (5) PM/dMSCs/PRP. From scanning electron microscope images, PM had a three-dimensional nanostructure, and dMSCs attached on the surface of PM. At 2, 4, and 8 weeks after implantation, each sample was collected from the graft area with a trephine bar and assessed by histologic and histomorphometric analyses. It was observed that the bone regenerated by PM/dMSCs/PRP was of excellent quality, and mature bone had been formed. Histometrically, at 8 weeks, newly formed bone areas comprised 12.39 +/- 1.29% (control), 25.28 +/- 3.92% (PM), 27.72 +/- 3.15% (PM/PRP), 50.07 +/- 3.97% (PM/dMSCs), and 58.43 +/- 5.06% (PM/dMSCs/PRP). The PM/dMSCs and PM/dMSCs/PRP groups showed a significant increase at all weeks compared with the control, PM, or PM/PRP (P < 0.05 at 2, 4, and 8 weeks, analysis of variance). These results showed that MSCs might keep their own potential and promote new bone regeneration in the three-dimensional structure by PM scaffolds. Taken together, it is suggested that PM might be useful as a scaffold of bone regeneration in cell therapy, and these results might lead to an effective treatment method for bone defects. PMID: 19816290 [PubMed - as supplied by publisher] |
| Metabolic Remodeling Induced by Mitochondrial Aldehyde Stress Stimulates Tolerance to Oxidative Stress in the Heart.
October 10, 2009 at 7:06 am
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| | Metabolic Remodeling Induced by Mitochondrial Aldehyde Stress Stimulates Tolerance to Oxidative Stress in the Heart. Circ Res. 2009 Oct 8; Authors: Endo J, Sano M, Katayama T, Hishiki T, Shinmura K, Morizane S, Matsuhashi T, Katsumata Y, Zhang Y, Ito H, Nagahata Y, Marchitti S, Nishimaki K, Wolf AM, Nakanishi H, Hattori F, Vasiliou V, Adachi T, Ohsawa I, Taguchi R, Hirabayashi Y, Ohta S, Suematsu M, Ogawa S, Fukuda K Rationale: Aldehyde accumulation is regarded as a pathognomonic feature of oxidative stress-associated cardiovascular disease. Objective: We investigated how the heart compensates for the accelerated accumulation of aldehydes. Methods and Results: Aldehyde dehydrogenase 2 (ALDH2) has a major role in aldehyde detoxification in the mitochondria, a major source of aldehydes. Transgenic (Tg) mice carrying an Aldh2 gene with a single nucleotide polymorphism (Aldh2*2) were developed. This polymorphism has a dominant-negative effect and the Tg mice exhibited impaired ALDH activity against a broad range of aldehydes. Despite a shift toward the oxidative state in mitochondrial matrices, Aldh2*2 Tg hearts displayed normal left ventricular function by echocardiography and, because of metabolic remodeling, an unexpected tolerance to oxidative stress induced by ischemia/reperfusion injury. Mitochondrial aldehyde stress stimulated eukaryotic translation initiation factor 2alpha phosphorylation. Subsequent translational and transcriptional activation of activating transcription factor-4 promoted the expression of enzymes involved in amino acid biosynthesis and transport, ultimately providing precursor amino acids for glutathione biosynthesis. Intracellular glutathione levels were increased 1.37-fold in Aldh2*2 Tg hearts compared with wild-type controls. Heterozygous knockout of Atf4 blunted the increase in intracellular glutathione levels in Aldh2*2 Tg hearts, thereby attenuating the oxidative stress-resistant phenotype. Furthermore, glycolysis and NADPH generation via the pentose phosphate pathway were activated in Aldh2*2 Tg hearts. (NADPH is required for the recycling of oxidized glutathione.) Conclusions: The findings of the present study indicate that mitochondrial aldehyde stress in the heart induces metabolic remodeling, leading to activation of the glutathione-redox cycle, which confers resistance against acute oxidative stress induced by ischemia/reperfusion. PMID: 19815821 [PubMed - as supplied by publisher] |
| Embryonic stem cell-like cells derived from adult human testis.
October 10, 2009 at 7:06 am
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| | Embryonic stem cell-like cells derived from adult human testis. Hum Reprod. 2009 Oct 8; Authors: Mizrak SC, Chikhovskaya JV, Sadri-Ardekani H, van Daalen S, Korver CM, Hovingh SE, Roepers-Gajadien HL, Raya A, Fluiter K, de Reijke TM, de la Rosette JJ, Knegt AC, Belmonte JC, van der Veen F, de Rooij DG, Repping S, van Pelt AM BACKGROUND Given the significant drawbacks of using human embryonic stem (hES) cells for regenerative medicine, the search for alternative sources of multipotent cells is ongoing. Studies in mice have shown that multipotent ES-like cells can be derived from neonatal and adult testis. Here we report the derivation of ES-like cells from adult human testis. METHODS Testis material was donated for research by four men undergoing bilateral castration as part of prostate cancer treatment. Testicular cells were cultured using StemPro medium. Colonies that appeared sharp edged and compact were collected and subcultured under hES-specific conditions. Molecular characterization of these colonies was performed using RT-PCR and immunohistochemistry. (Epi)genetic stability was tested using bisulphite sequencing and karyotype analysis. Directed differentiation protocols in vitro were performed to investigate the potency of these cells and the cells were injected into immunocompromised mice to investigate their tumorigenicity. RESULTS In testicular cell cultures from all four men, sharp-edged and compact colonies appeared between 3 and 8 weeks. Subcultured cells from these colonies showed alkaline phosphatase activity and expressed hES cell-specific genes (Pou5f1, Sox2, Cripto1, Dnmt3b), proteins and carbohydrate antigens (POU5F1, NANOG, SOX2 and TRA-1-60, TRA-1-81, SSEA4). These ES-like cells were able to differentiate in vitro into derivatives of all three germ layers including neural, epithelial, osteogenic, myogenic, adipocyte and pancreatic lineages. The pancreatic beta cells were able to produce insulin in response to glucose and osteogenic-differentiated cells showed deposition of phosphate and calcium, demonstrating their functional capacity. Although we observed small areas with differentiated cell types of human origin, we never observed extensive teratomas upon injection of testis-derived ES-like cells into immunocompromised mice. CONCLUSIONS Multipotent cells can be established from adult human testis. Their easy accessibility and ethical acceptability as well as their non-tumorigenic and autogenic nature make these cells an attractive alternative to human ES cells for future stem cell therapies. PMID: 19815622 [PubMed - as supplied by publisher] |
| Visualization of gene expression in the live subject using the Na/I symporter as a reporter gene: applications in biotherapy.
October 10, 2009 at 7:06 am
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| | Visualization of gene expression in the live subject using the Na/I symporter as a reporter gene: applications in biotherapy. Br J Pharmacol. 2009 Oct 8; Authors: Baril P, Martin-Duque P, Vassaux G Biotherapies involve the utilization of antibodies, genetically modified viruses, bacteria or cells for therapeutic purposes. Molecular imaging has the potential to provide unique information that will guarantee their biosafety in humans and provide a rationale for the future development of new generations of reagents. In this context, non-invasive imaging of gene expression is an attractive prospect, allowing precise, spacio-temporal measurements of gene expression in longitudinal studies involving gene transfer vectors. With the emergence of cell therapies in regenerative medicine, it is also possible to track cells injected into subjects. In this context, the Na/I symporter (NIS) has been used in preclinical studies. Associated with a relevant radiotracer ((123)I(-), (124)I(-), (99m)TcO4(-)), NIS can be used to monitor gene transfer and the spread of selectively replicative viruses in tumours as well as in cells with a therapeutic potential. In addition to its imaging potential, NIS can be used as a therapeutic transgene through its ability to concentrate therapeutic doses of radionuclides in target cells. This dual property has applications in cancer treatment and could also be used to eradicate cells with therapeutic potential in the case of adverse events. Through experience acquired in preclinical studies, we can expect that non-invasive molecular imaging using NIS as a transgene will be pivotal for monitoring in vivo the exact distribution and pharmacodynamics of gene expression in a precise and quantitative way. This review highlights the applications of NIS in biotherapy, with a particular emphasis on image-guided radiotherapy, monitoring of gene and vector biodistribution and trafficking of stem cells. PMID: 19814733 [PubMed - as supplied by publisher] |
| PEGDA hydrogels with patterned elasticity: Novel tools for the study of cell response to substrate rigidity.
October 10, 2009 at 6:58 am
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| | PEGDA hydrogels with patterned elasticity: Novel tools for the study of cell response to substrate rigidity. Biotechnol Bioeng. 2009 Oct 8; Authors: Nemir S, Hayenga HN, West JL The ability of cells to migrate in response to mechanical gradients (durotaxis) and differential cell behavior in adhesion, spreading, and proliferation in response to substrate rigidity are key factors both in tissue engineering, in which materials must be selected to provide the appropriate mechanical signals, and in studies of mechanisms of diseases such as cancer and atherosclerosis, in which changes in tissue stiffness may inform cell behavior. Using poly(ethylene glycol) diacrylate hydrogels with varying polymer chain length and photolithographic patterning techniques, we are able to provide substrates with spatially patterned, tunable mechanical properties in both gradients and distinct patterns. The hydrogels can be patterned to produce anisotropic structures and exhibit patterned strain under mechanical loading. These hydrogels may be used to study cell response to substrate rigidity in both two and three dimensions and can also be used as a scaffold in tissue engineering applications. (c) 2009 Wiley Periodicals, Inc. PMID: 19816965 [PubMed - as supplied by publisher] |
| Synthetic Materials in the Study of Cell Response to Substrate Rigidity.
October 10, 2009 at 6:58 am
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| | Synthetic Materials in the Study of Cell Response to Substrate Rigidity. Ann Biomed Eng. 2009 Oct 9; Authors: Nemir S, West JL While it has long been understood that cells can sense and respond to a variety of stimuli, including soluble and insoluble factors, light, and externally applied mechanical stresses, the extent to which cells can sense and respond to the mechanical properties of their environment has only recently begun to be studied. Cell response to substrate stiffness has been suggested to play an important role in processes ranging from developmental morphogenesis to the pathogenesis of disease states and may have profound implications for cell and tissue culture and tissue engineering. Given the importance of this phenomenon, there is a clear need for systems for cell study in which substrate mechanics can be carefully defined and varied independently of biochemical and other signals. This review will highlight past work in the field of cell response to substrate rigidity as well as areas for future study. PMID: 19816774 [PubMed - as supplied by publisher] |
| Transforming Growth Factor-beta Isoforms and the Induction of Bone Formation: Implications for Reconstructive Craniofacial Surgery.
October 10, 2009 at 6:58 am
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| | Transforming Growth Factor-beta Isoforms and the Induction of Bone Formation: Implications for Reconstructive Craniofacial Surgery. J Craniofac Surg. 2009 Sep;20(5):1544-55 Authors: Ripamonti U, Ferretti C, Teare J, Blann L Craniofacial skeletal reconstruction remains a challenging problem despite major molecular and surgical developments in the understanding of bone formation by induction. The induction of bone formation has been a critical topic of research across the planet. The bone induction principle identified important cues for tissue engineering of bone, namely, osteogenic soluble molecular signals, the bone morphogenetic and osteogenic proteins, and insoluble signals or substrata including biomimetic bioactive matrices and responding stem cells. In primates, and in primates only, the osteogenic soluble molecular signals that initiate the induction of bone formation additionally include the 3 mammalian transforming growth factor-beta (TGF-beta) isoforms, members of the TGF-beta supergene family. The mammalian TGF-beta isoforms, when implanted in the rectus abdominis muscle of the nonhuman primate Papio ursinus, induce rapid and substantial endochondral bone formation resulting in large corticalized ossicles by day 30 after heterotopic implantation; in calvarial defects of the same nonhuman primates, identical or higher doses of the TGF-beta protein do not induce bone formation because of the overexpression of Smad-6 and Smad-7, gene product inhibitors of the TGF-beta signaling pathway. The addition of minced fragments of autogenous rectus abdominis muscle partially restores the osteoinductive activity of the human TGF-beta3 isoform resulting in the induction of bone formation in the treated calvarial defects. Recombinant human TGF-beta3 delivered by Matrigel matrix and implanted in class II and III furcation defects of mandibular molars of P. ursinus induce periodontal tissue regeneration. The addition of minced fragments of autogenous rectus abdominis muscle significantly enhances cementogenesis. This review highlights the induction of bone formation by the osteogenic proteins of the TGF-beta superfamily in the nonhuman primate P. ursinus and reviews combinatorial applications of myoblastic/myogenic stem cell-based therapeutics for bone induction and morphogenesis. The recruitment of myoendothelial cells is also discussed in the light of the intrinsic and spontaneous induction of bone formation by smart biomaterial matrices that induce bone differentiation in heterotopic extraskeletal sites of P. ursinus without the exogenous application of the osteogenic soluble molecular signals of the TGF-beta superfamily. PMID: 19816294 [PubMed - in process] |
| Bone tissue engineering scaffolds of today and tomorrow.
October 10, 2009 at 6:58 am
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| | Bone tissue engineering scaffolds of today and tomorrow. J Craniofac Surg. 2009 Sep;20(5):1531-2 Authors: Panetta NJ, Gupta DM, Longaker MT PMID: 19816291 [PubMed - in process] |
| Self-Assembling Peptide Nanofiber Scaffolds, Platelet-Rich Plasma, and Mesenchymal Stem Cells for Injectable Bone Regeneration With Tissue Engineering.
October 10, 2009 at 6:58 am
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| | Self-Assembling Peptide Nanofiber Scaffolds, Platelet-Rich Plasma, and Mesenchymal Stem Cells for Injectable Bone Regeneration With Tissue Engineering. J Craniofac Surg. 2009 Sep;20(5):1523-1530 Authors: Yoshimi R, Yamada Y, Ito K, Nakamura S, Abe A, Nagasaka T, Okabe K, Kohgo T, Baba S, Ueda M The purpose of this study was to investigate a capability of PuraMatrix (PM), which is a self-assembling peptide nanomaterial, as a scaffold for bone regeneration in combination with dog mesenchymal stem cells (dMSCs) and/or platelet-rich plasma (PRP) using tissue engineering and regenerative technology. Initially, teeth were extracted from an adult hybrid dog's mandible region. After 4 weeks, bone defects were prepared on both sides of the mandible with a trephine bar. The following graft materials were implanted into these defects: (1) control (defect only), (2) PM, (3) PM/PRP, (4) PM/dMSCs, and (5) PM/dMSCs/PRP. From scanning electron microscope images, PM had a three-dimensional nanostructure, and dMSCs attached on the surface of PM. At 2, 4, and 8 weeks after implantation, each sample was collected from the graft area with a trephine bar and assessed by histologic and histomorphometric analyses. It was observed that the bone regenerated by PM/dMSCs/PRP was of excellent quality, and mature bone had been formed. Histometrically, at 8 weeks, newly formed bone areas comprised 12.39 +/- 1.29% (control), 25.28 +/- 3.92% (PM), 27.72 +/- 3.15% (PM/PRP), 50.07 +/- 3.97% (PM/dMSCs), and 58.43 +/- 5.06% (PM/dMSCs/PRP). The PM/dMSCs and PM/dMSCs/PRP groups showed a significant increase at all weeks compared with the control, PM, or PM/PRP (P < 0.05 at 2, 4, and 8 weeks, analysis of variance). These results showed that MSCs might keep their own potential and promote new bone regeneration in the three-dimensional structure by PM scaffolds. Taken together, it is suggested that PM might be useful as a scaffold of bone regeneration in cell therapy, and these results might lead to an effective treatment method for bone defects. PMID: 19816290 [PubMed - as supplied by publisher] |
| The osteogenic differentiation of adult bone marrow and perinatal umbilical mesenchymal stem cells and matrix remodelling in three-dimensional collagen scaffolds.
October 10, 2009 at 6:58 am
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| | The osteogenic differentiation of adult bone marrow and perinatal umbilical mesenchymal stem cells and matrix remodelling in three-dimensional collagen scaffolds. Biomaterials. 2009 Oct 6; Authors: Schneider RK, Puellen A, Kramann R, Raupach K, Bornemann J, Knuechel R, Pérez-Bouza A, Neuss S Adult human mesenchymal stem cells from bone marrow (BM-MSC) represent a promising source for skeletal regeneration. Perinatal MSC from Wharton's Jelly of the umbilical cord (UC-MSC) are expected to possess enhanced differentiation capacities due to partial expression of pluripotency markers. For bone tissue engineering, it is important to analyse in vitro behaviour of stem cell/biomaterial hybrids concerning in vivo integration into injured tissue via migration, matrix remodelling and differentiation. This study compares the cell-mediated remodelling of three-dimensional collagen I/III gels during osteogenic differentiation of both cell types. When activated through collagen contact and subjected to osteogenic differentiation, UC-MSC differ from BM-MSC in expression and synthesis of extracellular matrix (ECM) proteins as shown by histology, immunohistochemistry, Western Blot analysis and realtime-RT-PCR. The biosynthetic activity was accompanied in both cell types by the ultrastructural appearance of hydroxyapatite/calcium crystals and osteogenic gene induction. Following secretion of matrix metalloproteinases (MMP), both MSC types migrated into and colonised the collagenous matrix causing matrix strengthening and contraction. These results indicate that UC-MSC and BM-MSC display all features needed for effective bone fracture healing. The expression of ECM differs in both cell types considerably, suggesting different mechanisms for bone formation and significant impact for bone tissue engineering. PMID: 19815272 [PubMed - as supplied by publisher] |
| Shape, loading, and motion in the bioengineering design, fabrication, and testing of personalized synovial joints.
October 10, 2009 at 6:58 am
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| | Shape, loading, and motion in the bioengineering design, fabrication, and testing of personalized synovial joints. J Biomech. 2009 Oct 6; Authors: Williams GM, Chan EF, Temple-Wong MM, Bae WC, Masuda K, Bugbee WD, Sah RL With continued development and improvement of tissue engineering therapies for small articular lesions, increased attention is being focused on the challenge of engineering partial or whole synovial joints. Joint-scale constructs could have applications in the treatment of large areas of articular damage or in biological arthroplasty of severely degenerate joints. This review considers the roles of shape, loading and motion in synovial joint mechanobiology and their incorporation into the design, fabrication, and testing of engineered partial or whole joints. Incidence of degeneration, degree of impairment, and efficacy of current treatments are critical factors in choosing a target for joint bioengineering. The form and function of native joints may guide the design of engineered joint-scale constructs with respect to size, shape, and maturity. Fabrication challenges for joint-scale engineering include controlling chemo-mechano-biological microenvironments to promote the development and growth of multiple tissues with integrated interfaces or lubricated surfaces into anatomical shapes, and developing joint-scale bioreactors which nurture and stimulate the tissue with loading and motion. Finally, evaluation of load-bearing and tribological properties can range from tissue to joint scale and can focus on biological structure at present or after adaptation. PMID: 19815214 [PubMed - as supplied by publisher] |
| Emergent morphogenesis: Elastic mechanics of a self-deforming tissue.
October 10, 2009 at 6:58 am
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| | Emergent morphogenesis: Elastic mechanics of a self-deforming tissue. J Biomech. 2009 Oct 6; Authors: Davidson LA, Joshi SD, Kim HY, von Dassow M, Zhang L, Zhou J Multicellular organisms are generated by coordinated cell movements during morphogenesis. Convergent extension is a key tissue movement that organizes mesoderm, ectoderm, and endoderm in vertebrate embryos. The goals of researchers studying convergent extension, and morphogenesis in general, include understanding the molecular pathways that control cell identity, establish fields of cell types, and regulate cell behaviors. Cell identity, the size and boundaries of tissues, and the behaviors exhibited by those cells shape the developing embryo; however, there is a fundamental gap between understanding the molecular pathways that control processes within single cells and understanding how cells work together to assemble multicellular structures. Theoretical and experimental biomechanics of embryonic tissues are increasingly being used to bridge that gap. The efforts to map molecular pathways and the mechanical processes underlying morphogenesis are crucial to understanding: (1) the source of birth defects, (2) the formation of tumors and progression of cancer, and (3) basic principles of tissue engineering. In this paper, we first review the process of tissue convergent extension of the vertebrate axis and then review models used to study the self-organizing movements from a mechanical perspective. We conclude by presenting a relatively simple "wedge-model" that exhibits key emergent properties of convergent extension such as the coupling between tissue stiffness, cell intercalation forces, and tissue elongation forces. PMID: 19815213 [PubMed - as supplied by publisher] |
| [Study on cryopreservation of tissue engineered tendon by vitrification]
October 10, 2009 at 6:58 am
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| | [Study on cryopreservation of tissue engineered tendon by vitrification] Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2009 Aug;26(4):847-51 Authors: Liu C, Qin T, Wang Z, Chen X, Yang Z In search of a practical method for the cryopreservation of tissue engineered tendon (TET) by vitrification, we adopted 3 kinds of different cryoprotective agents (CPA)(21% DMSO, DP6 and VS55) in studying the freeze-stored effect of different CPA. The cellular morphology and post-thaw viability of the TET were examined by scanning electron microscopy (SEM), flow cytometry, and confocal laser microscopy (CLM). The results showed that there existed statistically significant difference in respect to the post-thaw viability between 21% DMSO and DP6, VS55; The cells specially adhered to the surface of scaffold both before or after cryopreservation by use of 21% DMSO. It was suggested that 21% DMSO as a CPA for TET cryopreservation was better than DP6 and VS55 in the current study. PMID: 19813624 [PubMed - in process] |
| Molecular and cellular determinants for generating ES-cell derived dopamine neurons for cell therapy.
October 10, 2009 at 6:58 am
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| | Molecular and cellular determinants for generating ES-cell derived dopamine neurons for cell therapy. Adv Exp Med Biol. 2009;651:112-23 Authors: Pruszak J, Isacson O Embryonic stem (ES) cells can generate midbrain dopaminergic (DA) neuronal phenotypes in vitro and have been successfully applied to restore function in animal models of Parkinson's disease (PD). How can we best integrate our growinginsight into the regulatory cascade of transcription factors guiding midbrain specification to further improve the in vitro differentiation of midbrain DA neurons for cell therapy of PD? To characterize the differentiation of authentic DA neurons in vitro, expression patterns of the numerous midbrain-characteristic markers need to be investigated. When using forced gene expression, such factors have to be closely monitored to avoid generation of nonphysiological cell types. Fluorescent markers such as Pitx3-GFP, TH-GFP, Sox1-GFP or surface antigens have proven useful for elimination of unwanted cell types by cell sorting, thereby averting tumors and increasing the DA fraction for transplantation studies. The importance of appropriate timing during application of extrinsic factors and the influence of cell-cell interactions in the dish has to be taken into account. This conceptual synopsis outlines current objectives, progress, but also challenges, in deriving midbrain DA neurons from pluripotent stem cells for clinical and scientific applications. PMID: 19731556 [PubMed - indexed for MEDLINE] |
| Development and engineering of dopamine neurons. Preface.
October 10, 2009 at 6:58 am
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| | Development and engineering of dopamine neurons. Preface. Adv Exp Med Biol. 2009;651:v-vi Authors: Pasterkamp RJ, Smidt MP, Burbach JP PMID: 19731545 [PubMed - indexed for MEDLINE] |
| High-throughput measurements of hydrogel tissue construct mechanics.
October 10, 2009 at 6:58 am
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| | High-throughput measurements of hydrogel tissue construct mechanics. Tissue Eng Part C Methods. 2009 Jun;15(2):181-90 Authors: Marquez JP, Legant W, Lam V, Cayemberg A, Elson E, Wakatsuki T Engineered tissues represent a natural environment for studying cell physiology, mechanics, and function. Cellular interactions with the extracellular matrix proteins are important determinants of cell physiology and tissue mechanics. Dysregulation of these parameters can result in diseases such as cardiac fibrosis and atherosclerosis. In this report we present a novel system to produce hydrogel tissue constructs (HTCs) and to characterize their mechanical properties. HTCs are grown in custom chambers and a robotic system is used to indent them and measure the resulting forces. Force measurements are then used to estimate HTC pretension (cellular contractility). Pretension was reduced in a dose-dependent manner by cytochalasin D (CD) treatment; the highest concentration (2microM) resulted in 10-fold decrease. On the other hand, treatment with fetal bovine serum (20%) resulted in approximately threefold increase in pretension. Excellent repeatability and precision were observed in measurements from replicate HTCs. The coefficient of statistical variance of quantified pretension ranged from 7% to 15% (n=4). Due to the small size (4x4x0.8mm) of the HTCs, this system of profiling HTC mechanics can readily be used in high-throughput applications. In particular, it can be used for screening chemical libraries in search of drugs that can alter tissue mechanics. PMID: 19196123 [PubMed - indexed for MEDLINE] |
| California Treasurer Says Stem Cell Agency to Receive $118.5 Million
October 9, 2009 at 8:00 pm
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| | The California State Treasurer's office this afternoon confirmed that the California stem cell agency will receive $118.5 million in fresh cash from the state's latest bond sale. It was good news for CIRM, which faced the prospect of running out of money by the end of next year, and a change from what was expected earlier this week. Tom Dresslar, spokesman for the treasurer, verified the figure | | | 
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