| The Lucky 11 and $167 Million in Stem Cell Research Cash
October 23, 2009 at 6:00 pm
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| | The California stem cell agency has pinpointed 11 likely winners of grants and loans up to $20 million each in the agency's ambitious disease team round, which was once projected at $210 million.The awards are scheduled to be formally approved next week by the CIRM board of directors at a two-day meeting in Los Angeles at the Luxe Hotel. CIRM's Grants Working Group decided earlier that 11 |
| Regulation of stemness and stem cell niche of mesenchymal stem cells: Implications in tumorigenesis and metastasis.
October 23, 2009 at 6:16 am
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| | Regulation of stemness and stem cell niche of mesenchymal stem cells: Implications in tumorigenesis and metastasis. J Cell Physiol. 2009 Oct 21; Authors: Kuhn NZ, Tuan RS Human mesenchymal stem cells (MSCs) derived from adult tissues have been considered a candidate cell type for cell-based tissue engineering and regenerative medicine. These multipotent cells have the ability to differentiate along several mesenchymal lineages and possibly along non-mesenchymal lineages. MSCs possess considerable immunosuppressive properties that can influence the surrounding tissue positively during regeneration, but perhaps negatively towards the pathogenesis of cancer and metastasis. The balance between the naïve stem state and differentiation is highly dependent on the stem cell niche. Identification of stem cell niche components has helped to elucidate the mechanisms of stem cell maintenance and differentiation. Ultimately, the fate of stem cells is dictated by their microenvironment. In this review, we describe the identification and characterization of bone marrow-derived MSCs, the properties of the bone marrow stem cell niche, and the possibility and likelihood of MSC involvement in cancer progression and metastasis. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc. PMID: 19847802 [PubMed - as supplied by publisher] |
| In vivo imaging of hematopoietic stem cells and their microenvironment.
October 23, 2009 at 6:16 am
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| | In vivo imaging of hematopoietic stem cells and their microenvironment. J Biophotonics. 2009 Oct 21;2(11):619-631 Authors: Celso CL, Wu JW, Lin CP In this review we provide a description of the basic concepts and paradigms currently constituting the foundations of adult stem cell biology, and discuss the role that live imaging techniques have in the development of the field. We focus on live imaging of hematopoietic stem cells (HSCs) as the basic biology and clinical applications of HSCs have historically been at the forefront of the stem cell field, and HSC are the first mammalian tissue stem cells to be visualized in vivo using advanced light microscopy techniques. We outline the current technical challenges that remain to be overcome before stem cells and their niche can be more fully characterized using the live imaging technology. ((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). PMID: 19847800 [PubMed - as supplied by publisher] |
| Biophotonics and Regenerative Medicine - ideal partners for research in the 21(st) Century.
October 23, 2009 at 6:16 am
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| | Biophotonics and Regenerative Medicine - ideal partners for research in the 21(st) Century. J Biophotonics. 2009 Oct 21;2(11):613-614 Authors: Huser T, Wilson B, Matthews DL PMID: 19847797 [PubMed - as supplied by publisher] |
| Regenerative Medicine Special Feature: Interrogating functional integration between injected pluripotent stem cell-derived cells and surrogate cardiac tissue.
October 23, 2009 at 6:16 am
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| | Regenerative Medicine Special Feature: Interrogating functional integration between injected pluripotent stem cell-derived cells and surrogate cardiac tissue. Proc Natl Acad Sci U S A. 2009 Oct 21; Authors: Song H, Yoon C, Kattman SJ, Dengler J, Massé S, Thavaratnam T, Gewarges M, Nanthakumar K, Rubart M, Keller GM, Radisic M, Zandstra PW Myocardial infarction resulting in irreversible loss of cardiomyocytes (CMs) remains a leading cause of heart failure. Although cell transplantation has modestly improved cardiac function, major challenges including increasing cell survival, engraftment, and functional integration with host tissue, remain. Embryonic stem cells (ESCs), which can be differentiated into cardiac progenitors (CPs) and CMs, represent a candidate cell source for cardiac cell therapy. However, it is not known what specific cell type or condition is the most appropriate for transplantation. This problem is exasperated by the lack of efficient and predictive strategies to screen the large numbers of parameters that may impact cell transplantation. We used a cardiac tissue model, engineered heart tissue (EHT), and quantitative molecular and electrophysiological analyses, to test transplantation conditions and specific cell populations for their potential to functionally integrate with the host tissue. In this study, we validated our analytical platform using contractile mouse neonatal CMs (nCMs) and noncontractile cardiac fibroblasts (cFBs), and screened for the integration potential of ESC-derived CMs and CPs (ESC-CMs and -CPs). Consistent with previous in vivo studies, cFB injection interfered with electrical signal propagation, whereas injected nCMs improved tissue function. Purified bioreactor-generated ESC-CMs exhibited a diminished capacity for electrophysiological integration; a result correlated with lower (compared with nCMs) connexin 43 expression. ESC-CPs, however, appeared able to appropriately mature and integrate into EHT, enhancing the amplitude of tissue contraction. Our results support the use of EHT as a model system to accelerate development of cardiac cell therapy strategies. PMID: 19846783 [PubMed - as supplied by publisher] |
| An artificial extracellular matrix created by hepatocyte growth factor fused to IgG-Fc.
October 23, 2009 at 6:16 am
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| | An artificial extracellular matrix created by hepatocyte growth factor fused to IgG-Fc. Biomaterials. 2009 Oct 19; Authors: Azuma K, Nagaoka M, Cho CS, Akaike T The design of artificial extracellular matrices (ECM) has attracted much attention in tissue engineering and regenerative medicine as well as in molecular biology research. A recombinant hepatocyte growth factor (HGF), fused to an immunoglobulin G (IgG) Fc region (abbreviated as AeHGF-Fc) was constructed and confirmed by Western blot assay. Almost similar amounts of HepG2 cells adhered to AeHGF-Fc-coated surface compared to collagen-coated one with large morphological changes. Immobilized AeHGF-Fc continuously activated Akt in HepG2 cells whereas Akt activation induced by soluble HGF rapidly decreased with time, indicating that immobilized AeHGF-Fc follows different signal transduction pathways compared to soluble HGF. PMID: 19846215 [PubMed - as supplied by publisher] |
| Impact of Diabetes and Obesity on the Prostate and Urethra: Implications to Improved Bladder Dysfunction Understanding and Treatment.
October 23, 2009 at 6:16 am
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| | Impact of Diabetes and Obesity on the Prostate and Urethra: Implications to Improved Bladder Dysfunction Understanding and Treatment. J Urol. 2009 Oct 19; Authors: Christ GJ, Bushman W, Fraser MO PURPOSE: Alterations in bladder function are well documented in response to diabetes and obesity. Nonetheless, clinical manifestations of bladder dysfunction are diverse and the efficacy of available therapy is suboptimal. Since the bladder is only 1 component of the lower urinary tract, we explored existing evidence for the potential contribution(s) of other major lower urinary tract structures to diabetes and obesity related bladder dysfunction, namely the prostate and the urethra. MATERIALS AND METHODS: We performed a MEDLINE(R) database search of the relevant literature. RESULTS: A relatively large literature exists on bladder dysfunction and the urethra. However, when additional search terms were added, such as prostate, diabetes and obesity, there was a dramatic decrease in the number of retrieved citations. These observations are consistent with the vanishingly small available literature on the impact of diabetes on prostatic biology and urethral function, and their potential impact on bladder physiology/dysfunction. The available literature documents significant alterations in prostatic biology and urethral function in the setting of diabetes and/or obesity. CONCLUSIONS: The observed diversity in diabetes and obesity related bladder dysfunction, and the variable efficacy of currently available treatments may be related at least in part to the differential impact of these disease states on the complex integration of bladder function with other structural components of the lower urinary tract, namely the urethra and the prostate. More comprehensive investigations of this system should lead to improved understanding of the mechanistic basis for the observed pathophysiology and identify novel treatment regimens. PMID: 19846131 [PubMed - as supplied by publisher] |
| MAINTENANCE OF HUMAN HEPATOCYTE FUNCTION IN VITRO BY LIVER-DERIVED EXTRACELLULAR MATRIX GELS.
October 23, 2009 at 6:16 am
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| | MAINTENANCE OF HUMAN HEPATOCYTE FUNCTION IN VITRO BY LIVER-DERIVED EXTRACELLULAR MATRIX GELS. Tissue Eng Part A. 2009 Oct 21; Authors: Sellaro T, Ranade A, Faulk D, McCabe GP, Dorko K, Badylak SF, Strom S Tissue engineering and regenerative medicine (TE&RM) approaches to treating liver disease have the potential to provide temporary support with biohybrid liver-assist devices or long term therapy by replacing the diseased liver with functional constructs. A rate-limiting step for TE&RM strategies has been the loss of hepatocyte-specific functions after hepatocytes are isolated from their highly specialized in vivo microenvironment and placed in in vitro culture systems. The identification of a biologic substrate that can maintain a functional hepatocyte differentiation profile during in vitro culture would advance potential TE&RM therapeutic strategies. The present study compared two different biologic substrates for their ability to support human hepatocyte function in vitro: porcine liver-derived extracellular matrix (PLECM) or MatrigelTM. Because MatrigelTM has been shown to be the most useful matrix for static, traditional hepatocyte culture, we directly compared PLECM to MatrigelTM in each experiment. Albumin secretion, hepatic transport activity and ammonia metabolism were used to determine hepatocyte function. Hepatocytes cultured between two layers of PLECM or MatrigelTM showed equally high levels of albumin expression and secretion, ammonia metabolism and hepatic transporter expression and function. We conclude that like matrigel, PLECM represents a favorable substrate for in vitro culture of human hepatocytes. The present study compared three different biologic substrates for their ability to support human hepatocyte function in vitro: porcine liver-derived extracellular matrix (PLECM), Matrigel, and type-1 collagen. Albumin secretion, hepatic transport activity and ammonia metabolism were used as determinants of hepatocyte functionality. Hepatocytes cultured between two layers of PLECM or Matrigel showed higher levels of albumin secretion and ammonia metabolism compared to hepatocytes cultured on collagen. Hepatocytes cultured between two layers of PLECM maintained higher levels of hepatic transport activity compared to hepatocytes cultured in Matrigel sandwich or on type-1 collagen. We conclude that PLECM represents a favorable substrate for in vitro culture of human hepatocytes compared to Matrigel or type I collagen. PMID: 19845461 [PubMed - as supplied by publisher] |
| Autologous adipose-derived regenerative cells for therapeutic angiogenesis.
October 23, 2009 at 6:06 am
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| | Autologous adipose-derived regenerative cells for therapeutic angiogenesis. Curr Pharm Des. 2009;15(24):2784-90 Authors: Murohara T, Shintani S, Kondo K Therapeutic angiogenesis is an important means to salvage tissues against severe ischemic diseases in patients with no option for other vascular intervention. A number of recent studies implicated potentials of cell-based therapeutic angiogenesis using autologous bone marrow mononuclear cells, CD34(+) cells, peripheral blood mononuclear cells, and so on. Subcutaneous adipose tissues can be harvested by relatively easy methods. Recent studies indicated that adipose tissues contain progenitor cells or regenerative cells that can give rise to several mesenchymal lineages. Moreover, these progenitor cells can release multiple angiogenic growth factors and cytokines/chomokines including vascular endothelial growth factor (VEGF), hypatocyte growth factor (HGF) and chemokine stromal cell-derived factor-1 (SDF-1). The combination of these biological properties of adipose-derived regenerative cells (ADRCs) implicates that autologous adipose tissue will be a useful cell source for therapeutic angiogenesis in the next generation. PMID: 19689349 [PubMed - indexed for MEDLINE] |
| Regulation of stemness and stem cell niche of mesenchymal stem cells: Implications in tumorigenesis and metastasis.
October 23, 2009 at 6:05 am
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| | Regulation of stemness and stem cell niche of mesenchymal stem cells: Implications in tumorigenesis and metastasis. J Cell Physiol. 2009 Oct 21; Authors: Kuhn NZ, Tuan RS Human mesenchymal stem cells (MSCs) derived from adult tissues have been considered a candidate cell type for cell-based tissue engineering and regenerative medicine. These multipotent cells have the ability to differentiate along several mesenchymal lineages and possibly along non-mesenchymal lineages. MSCs possess considerable immunosuppressive properties that can influence the surrounding tissue positively during regeneration, but perhaps negatively towards the pathogenesis of cancer and metastasis. The balance between the naïve stem state and differentiation is highly dependent on the stem cell niche. Identification of stem cell niche components has helped to elucidate the mechanisms of stem cell maintenance and differentiation. Ultimately, the fate of stem cells is dictated by their microenvironment. In this review, we describe the identification and characterization of bone marrow-derived MSCs, the properties of the bone marrow stem cell niche, and the possibility and likelihood of MSC involvement in cancer progression and metastasis. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc. PMID: 19847802 [PubMed - as supplied by publisher] |
| Electrospinning fibrous polymer scaffolds for tissue engineering and cell culture.
October 23, 2009 at 6:05 am
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| | Electrospinning fibrous polymer scaffolds for tissue engineering and cell culture. J Vis Exp. 2009;(32): Authors: Ifkovits JL, Sundararaghavan HG, Burdick JA As the field of tissue engineering evolves, there is a tremendous demand to produce more suitable materials and processing techniques in order to address the requirements (e.g., mechanics and vascularity) of more intricate organs and tissues. Electrospinning is a popular technique to create fibrous scaffolds that mimic the architecture and size scale of the native extracellular matrix. These fibrous scaffolds are also useful as cell culture substrates since the fibers can be used to direct cellular behavior, including stem cell differentiation (see extensive reviews by Mauck et al. and Sill et al. for more information). In this article, we describe the general process of electrospinning polymers and as an example, electrospin a reactive hyaluronic acid capable of crosslinking with light exposure (see Ifkovits et al. for a review on photocrosslinkable materials). We also introduce further processing capabilities such as photopatterning and multi-polymer scaffold formation. Photopatterning can be used to create scaffolds with channels and multi-scale porosity to increase cellular infiltration and tissue distribution. Multi-polymer scaffolds are useful to better tune the properties (mechanics and degradation) of a scaffold, including tailored porosity for cellular infiltration. Furthermore, these techniques can be extended to include a wide array of polymers and reactive macromers to create complex scaffolds that provide the cues necessary for the development of successful tissue engineered constructs. PMID: 19847151 [PubMed - in process] |
| Estimation of relationship between descriptors and cytotoxicity of newly synthesized 1,2,3,4-tetrahydroisoquinoline derivatives.
October 23, 2009 at 6:05 am
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| | Estimation of relationship between descriptors and cytotoxicity of newly synthesized 1,2,3,4-tetrahydroisoquinoline derivatives. Anticancer Res. 2009 Oct;29(10):4077-82 Authors: Ishihara M, Hatano H, Takekawa F, Kawase M, Sakagami H We recently demonstrated that the cytotoxicity of nineteen 1,2,3,4-tetrahydroisoquinoline derivatives depends on the molecular size (surface are, volume, width measured at 3-dimensional configuration), but not on most of the other electronic factors (Ishihara et al., Anticancer Res 29: 2265-2272, 2009). However, the information regarding cytotoxicity and molecular size in these compounds is limited. Here, a quantitative structure-activity relationship (QSAR) analysis using nineteen newly synthesized 1,2,3,4-tetrahydroisoquinoline derivatives was carried out. A semiempirical molecular-orbital method (CAChe 4.9, PM5) was applied to delineate the relationship between the cytotoxicity (evaluated by 50% cytotoxic concentration, CC(50)) of the nineteen derivatives (TD1-19) against human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4) cell lines and sixteen chemical descriptors determined by CONFLEX/PM5 method or the molecular weight. There was some correlation between the CC(50) and the dipole moment for HSC-4 cells (r(2)=0.273), between the CC and log P for HL-60 and HSC-3 cells (r(2) 50 =0.191-0.212), and between the CC(50) and distance of C-R(2) (at three dimensional configuration) (r(2)=0.394) and molecular weight (r(2)=0.292) for HL-60 cells. On the other hand, there was little or no correlation between the CC(50) and other descriptors. The present study demonstrated the dependency of the cytotoxicity of 1,2,3,4-tetrahydroisoquinoline derivatives on hydrophobicity and distance between C-R(2) in the 3-dimensional configuration. These descriptors obtained from the CONFLEX/PM5 method may be utilized as a tool to analyze the biological effect of 1,2,3,4-tetrahydroisoquinolines. PMID: 19846954 [PubMed - in process] |
| Zonal Chondrocyte Subpopulations Reacquire Zone-Specific Characteristics During In Vitro Redifferentiation.
October 23, 2009 at 6:05 am
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| | Zonal Chondrocyte Subpopulations Reacquire Zone-Specific Characteristics During In Vitro Redifferentiation. Am J Sports Med. 2009 Oct 21; Authors: Schuurman W, Gawlitta D, Klein TJ, Ten Hoope W, van Rijen MH, Dhert WJ, van Weeren PR, Malda J BACKGROUND: If chondrocytes from the superficial, middle, and deep zones of articular cartilage could maintain or regain their characteristic properties during in vitro culture, it would be feasible to create constructs comprising these distinctive zones. HYPOTHESIS: Zone-specific characteristics of zonal cell populations will disappear during 2-dimensional expansion but will reappear after 3-dimensional redifferentiation, independent of the culture technique used (alginate beads versus pellet culture). STUDY DESIGN: Controlled laboratory study. METHODS: Equine articular chondrocytes from the 3 zones were expanded in monolayer culture (8 donors) and subsequently redifferentiated in pellet and alginate bead cultures for up to 4 weeks. Glycosaminoglycans and DNA were quantified, along with immunohistochemical assessment of the expression of various zonal markers, including cartilage oligomeric protein (marking cells from the deeper zones) and clusterin (specifically expressed by superficial chondrocytes). RESULTS: Cell yield varied between zones, but proliferation rates did not show significant differences. Expression of all evaluated zonal markers was lost during expansion. Compared to the alginate bead cultures, pellet cultures showed a higher amount of glycosaminoglycans produced per DNA after redifferentiation. In contrast to cells in pellet cultures, cells in alginate beads regained zonal differences, as evidenced by zone-specific reappearance of cartilage oligomeric protein and clusterin, as well as significantly higher glycosaminoglycans production by cells from the deep zone compared to the superficial zone. CONCLUSION: Chondrocytes isolated from the 3 zones of equine cartilage can restore their zone-specific matrix expression when cultured in alginate after in vitro expansion. CLINICAL RELEVANCE: Appreciation of the zonal differences can lead to important advances in cartilage tissue engineering. Findings support the use of hydrogels such as alginate for engineering zonal cartilage constructs. PMID: 19846691 [PubMed - as supplied by publisher] |
| An artificial extracellular matrix created by hepatocyte growth factor fused to IgG-Fc.
October 23, 2009 at 6:05 am
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| | An artificial extracellular matrix created by hepatocyte growth factor fused to IgG-Fc. Biomaterials. 2009 Oct 19; Authors: Azuma K, Nagaoka M, Cho CS, Akaike T The design of artificial extracellular matrices (ECM) has attracted much attention in tissue engineering and regenerative medicine as well as in molecular biology research. A recombinant hepatocyte growth factor (HGF), fused to an immunoglobulin G (IgG) Fc region (abbreviated as AeHGF-Fc) was constructed and confirmed by Western blot assay. Almost similar amounts of HepG2 cells adhered to AeHGF-Fc-coated surface compared to collagen-coated one with large morphological changes. Immobilized AeHGF-Fc continuously activated Akt in HepG2 cells whereas Akt activation induced by soluble HGF rapidly decreased with time, indicating that immobilized AeHGF-Fc follows different signal transduction pathways compared to soluble HGF. PMID: 19846215 [PubMed - as supplied by publisher] |
| Endothelial Progenitor Populations in Differentiating Embryonic Stem Cells II: Drug Selection and Functional Characterization.
October 23, 2009 at 6:05 am
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| | Endothelial Progenitor Populations in Differentiating Embryonic Stem Cells II: Drug Selection and Functional Characterization. Tissue Eng Part A. 2009 Oct 21; Authors: Kim S, von Recum HA Despite the enormous potential of embryonic stem cells (ESCs) for use in tissue engineering and cell therapies, clinical use of ESCs has been deterred by difficulties in obtaining desired cell populations without undifferentiated or other undesired cell phenotypes. Previously we demonstrated the time-dependent variation of endothelial specific promoter activities in differentiating mouse embryonic stem cells (1). Here, we evaluated the functional behavior of endothelial cells (ECs) selected using a drug resistance gene (puromycinR) under the control of those different EC-promoters (Flk1, Tie1, and PECAM, as well as under VE-Cadherin (VEC)). All four promoters tested yielded cells with EC-specific protein expression and DiI-Ac-LDL uptake after puromycin treatment. However, the percentage of puromycin-surviving cells varied depending on EC-promoters indicating different levels of promoter activity. Continuous selection of ECs in puromycin reduced the presence of smooth muscle cells (SMCs) or undifferentiated cells. PuroR -selected cells under all of the EC-promoters were also positive for capillary-like network formation in MatrigelTM. Prostacyclin (PGI2) secretion by ESC-derived ECs showed improvement with orbital shear stress exposure corresponding to 0 - 16 dynes/cm2; however, PGI2 levels were lower than those seen in immortalized mouse endothelial cell lines. Tissue plasminogen activator (tPA) secretion by PuroR-selected cells was comparable to that seen in cell lines, but tPA secretion after shear stress exposure showed mixed results, with tPA increasing upon shear under PECAM and Tie1 promoters and tPA decreasing upon shear under Flk1 and VEC promoters. PMID: 19845466 [PubMed - as supplied by publisher] |
| Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: A canine model.
October 23, 2009 at 6:05 am
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| | Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: A canine model. Tissue Eng Part A. 2009 Oct 21; Authors: Ng KW, Lima EG, Bian L, O'Conor CJ, Jayabalan PS, Stoker AM, Kuroki K, Cook CR, Ateshian GA, Cook JL, Hung CT It was hypothesized that previously optimized serum-free culture conditions for juvenile bovine chondrocytes could be adapted to generate engineered cartilage with physiologic mechanical properties in a preclinical, adult canine model. Primary or passaged (using growth factors), adult chondrocytes from three canines were encapsulated in agarose, and cultured in serum-free media with TGF-beta3. After 28 days in culture, engineered cartilage formed by primary chondrocytes exhibited only small increases in GAG content. However, all passaged chondrocytes on day 28 elaborated a cartilage matrix with compressive properties and GAG content in the range of native, adult, canine cartilage values. A preliminary biocompatibility study utilizing chondral and osteochondral constructs showed no gross or histological signs of rejection, with all implanted constructs showing excellent integration with surrounding cartilage and subchondral bone. This study demonstrates that adult canine chondrocytes can form a mechanically functional, biocompatible, engineered cartilage tissue under optimized culture conditions. The encouraging findings of this work highlight the potential for tissue engineering strategies using adult chondrocytes in the clinical treatment of cartilage defects. PMID: 19845465 [PubMed - as supplied by publisher] |
| Tissue Engineering of the ACL - SDS Chemically Acellularized and Revitalized Tendons are Inferior to Native Tendons.
October 23, 2009 at 6:05 am
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| | Tissue Engineering of the ACL - SDS Chemically Acellularized and Revitalized Tendons are Inferior to Native Tendons. Tissue Eng Part A. 2009 Oct 21; Authors: Tischer T, Aryee S, Wexel G, Steinhauser E, Adamczyk C, Eichhorn S, Milz S, Martinek V, Gansbacher B, Imhoff AB, Vogt S The acellularization of tendons using detergents (sodium dodecyl sulfate (SDS), Triton-X, tri-nitro-butyl-phosphate (TnBP)) is a new source of scaffolds for tissue engineering in anterior cruciate ligament (ACL) repair. While in vitro testing demonstrated that acellular tendon scaffolds are biocompatible and show good biomechanical properties, in vivo confirmation of these results is not yet available. Therefore, the aim of this study was to see in vivo, if an acellular allogenic construct, colonized with autologous fibroblasts improves the quality of ACL reconstruction. ACL replacement was performed in 31 NZW rabbits using a standardized model. Fifteen animals received autologous semitendinosus tendon whereas 16 animals were treated with a tissue-engineered construct. This construct was made by acellularization of allogenic semitendinosus tendons using SDS and subsequent in vitro colonization with autologous fibroblasts. Eight weeks postoperatively, macroscopic, biomechanical (ultimate load to failure, elongation, stiffness; n=8/9), and histological (n=5) examinations were performed. Biomechanical testing showed decreasing strength of the constructs eight weeks after implantation compared to the direct post-surgical strength. However, tissue-engineered constructs (F = 19.7+/-20.3N) were significantly weaker than autologous tendons (F = 61.2+/-31.2N). Histologically, the autologous tendons showed signs of partial necrosis and of tissue remodelling. The tissue-engineered constructs exhibited an inflammatory reaction and showed both repopulated and acellular regions. In conclusion in vivo results were much more unfavorable than in vitro results had suggested. Further studies have to be performed to test if modifications of the acellularization process yield better results in vivo. PMID: 19845462 [PubMed - as supplied by publisher] |
| MAINTENANCE OF HUMAN HEPATOCYTE FUNCTION IN VITRO BY LIVER-DERIVED EXTRACELLULAR MATRIX GELS.
October 23, 2009 at 6:05 am
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| | MAINTENANCE OF HUMAN HEPATOCYTE FUNCTION IN VITRO BY LIVER-DERIVED EXTRACELLULAR MATRIX GELS. Tissue Eng Part A. 2009 Oct 21; Authors: Sellaro T, Ranade A, Faulk D, McCabe GP, Dorko K, Badylak SF, Strom S Tissue engineering and regenerative medicine (TE&RM) approaches to treating liver disease have the potential to provide temporary support with biohybrid liver-assist devices or long term therapy by replacing the diseased liver with functional constructs. A rate-limiting step for TE&RM strategies has been the loss of hepatocyte-specific functions after hepatocytes are isolated from their highly specialized in vivo microenvironment and placed in in vitro culture systems. The identification of a biologic substrate that can maintain a functional hepatocyte differentiation profile during in vitro culture would advance potential TE&RM therapeutic strategies. The present study compared two different biologic substrates for their ability to support human hepatocyte function in vitro: porcine liver-derived extracellular matrix (PLECM) or MatrigelTM. Because MatrigelTM has been shown to be the most useful matrix for static, traditional hepatocyte culture, we directly compared PLECM to MatrigelTM in each experiment. Albumin secretion, hepatic transport activity and ammonia metabolism were used to determine hepatocyte function. Hepatocytes cultured between two layers of PLECM or MatrigelTM showed equally high levels of albumin expression and secretion, ammonia metabolism and hepatic transporter expression and function. We conclude that like matrigel, PLECM represents a favorable substrate for in vitro culture of human hepatocytes. The present study compared three different biologic substrates for their ability to support human hepatocyte function in vitro: porcine liver-derived extracellular matrix (PLECM), Matrigel, and type-1 collagen. Albumin secretion, hepatic transport activity and ammonia metabolism were used as determinants of hepatocyte functionality. Hepatocytes cultured between two layers of PLECM or Matrigel showed higher levels of albumin secretion and ammonia metabolism compared to hepatocytes cultured on collagen. Hepatocytes cultured between two layers of PLECM maintained higher levels of hepatic transport activity compared to hepatocytes cultured in Matrigel sandwich or on type-1 collagen. We conclude that PLECM represents a favorable substrate for in vitro culture of human hepatocytes compared to Matrigel or type I collagen. PMID: 19845461 [PubMed - as supplied by publisher] |
| Cardiac applications for human pluripotent stem cells.
October 23, 2009 at 6:05 am
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| | Cardiac applications for human pluripotent stem cells. Curr Pharm Des. 2009;15(24):2791-806 Authors: Shiba Y, Hauch KD, Laflamme MA Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyocytes of potential use in cell-based cardiac therapies, high-throughput screening and safety testing of new drugs, and modeling human heart development. These stem cell-derived cardiomyocytes have an unambiguous cardiac phenotype and proliferate robustly both in vitro and in vivo. Recent transplantation studies in preclinical models have provided exciting proof-of-principle for their use in infarct repair and in the formation of a "biological pacemaker". While these successes give reason for cautious optimism, major challenges remain to the successful application of hESCs (or hiPSCs) to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. In this review, we describe the phenotype of hESC- and hiPSC-derived cardiomyocytes, the state of preclinical transplantation studies with these cells, and potential approaches to overcome the aforementioned hurdles. PMID: 19689350 [PubMed - indexed for MEDLINE] |
| Culture of nasal epithelial cells using chitosan-based membranes.
October 23, 2009 at 6:05 am
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| | Culture of nasal epithelial cells using chitosan-based membranes. Laryngoscope. 2009 Oct;119(10):2066-70 Authors: Huang TW, Young YH, Cheng PW, Chan YH, Young TH OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate whether chitosan-based membranes can be used as scaffolds for growth and differentiation of nasal epithelial cells (NECs). Our final goal was to establish a novel methodology for enhancing the regeneration of the respiratory system. STUDY DESIGN: Prospective study. METHODS: Human NECs were cultured on three various substrates, e.g., chitosan membranes, collagen, and chitosan-collagen membranes. Morphology of NECs was examined via light and electron microscopy, the area of ciliated cells was measured by confocal microscopy, and ciliary beat frequency was also evaluated. Expression of mucin genes was investigated with reverse-transcription polymerase chain reaction. RESULTS: NECs were found to be successfully adhesive with collagen and chitosan-collagen membranes at day 3 after seeding, but not with chitosan membranes. The cilia area on collagen were 6.1% +/- 1.2%, 8.4% +/- 1.4%, and 12.5% +/- 1.9% at days 7, 14, and 21 after confluence, respectively, compared with 5.1% +/- 0.9%, 8.6% +/- 1.6%, and 12.3% +/- 2.1% in chitosan-collagen membranes, exhibited nonsignificant difference (P > .05). There were no significant differences in ciliary beat frequency between each group. The expression levels of mucin genes, namely, MUC5AC, MUC5B, and MUC2, in NECs on both collagen and chitosan-collagen membranes did not differ significantly (P > .05). CONCLUSIONS: A small amount collagen mixed with chitosan substrate may improve the biocompatibility and promote the mucociliary differentiation in NECs. It appears that chitosan-collagen membrane is a promising scaffold for culture of the nasal epithelium, which sets the stage for studying tissue regeneration in the respiratory system. PMID: 19572267 [PubMed - indexed for MEDLINE] |
| Image analysis of soft-tissue in-growth and attachment into highly porous alumina ceramic foam metals.
October 23, 2009 at 6:05 am
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| | Image analysis of soft-tissue in-growth and attachment into highly porous alumina ceramic foam metals. Med Eng Phys. 2009 Sep;31(7):775-83 Authors: Khalil A, Aponte C, Zhang R, Davisson T, Dickey I, Engelman D, Hawkins M, Mason M The detailed quantitative characterization of soft-tissue in-growth into highly porous artificial implants is critical to understanding the biophysical processes that will lead to the best structural scaffolding construct. Previous studies have performed mechanical peel tests and mostly qualitative histological analyses of soft-tissue. The goal of this paper is to report the results obtained from applying two image analysis algorithms to quantify the morphological structure found in histological images of stained soft-tissue in-growth into alumina ceramic foam metal implants using a canine model. Three different pore sizes were used and three different post-operative time points were considered. Using the 2D Wavelet Transform Modulus Maxima method and 2D Fourier Transform analysis, a strong anisotropic signature (directional preference) is detected in early (4-week) histological samples. The direction of preference is towards the center of the implants. The strength of the anisotropy at later time points (8 and 16 weeks) becomes gradually weaker. Our interpretation is that after a short period of time, the main tissue growth activity has been concentrated on filling the artificial implant by growing towards its center. The weaker anisotropic signature found at later time points is interpreted as the tissue growth activity strengthening its structure by growing in more random directions. PMID: 19297233 [PubMed - indexed for MEDLINE] | | | 
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