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| Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration.
June 25, 2010 at 8:24 AM
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| | Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration. N Engl J Med. 2010 Jun 23; Authors: Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G BACKGROUND: Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal stem-cell deficiency. We investigated the long-term clinical results of cell therapy in patients with burn-related corneal destruction associated with limbal stem-cell deficiency, a highly disabling ocular disease. METHODS: We used autologous limbal stem cells cultivated on fibrin to treat 112 patients with corneal damage, most of whom had burn-dependent limbal stem-cell deficiency. Clinical results were assessed by means of Kaplan-Meier, Kruskal-Wallis, and univariate and multivariate logistic-regression analyses. We also assessed the clinical outcome according to the percentage of holoclone-forming stem cells, detected as cells that stain intensely (p63-bright cells) in the cultures. RESULTS: Permanent restoration of a transparent, renewing corneal epithelium was attained in 76.6% of eyes. The failures occurred within the first year. Restored eyes remained stable over time, with up to 10 years of follow-up (mean, 2.91+/-1.99; median, 1.93). In post hoc analyses, success - that is, the generation of normal epithelium on donor stroma - was associated with the percentage of p63-bright holoclone-forming stem cells in culture. Cultures in which p63-bright cells constituted more than 3% of the total number of clonogenic cells were associated with successful transplantation in 78% of patients. In contrast, cultures in which such cells made up 3% or less of the total number of cells were associated with successful transplantation in only 11% of patients. Graft failure was also associated with the type of initial ocular damage and postoperative complications. CONCLUSIONS: Cultures of limbal stem cells represent a source of cells for transplantation in the treatment of destruction of the human cornea due to burns. Copyright 2010 Massachusetts Medical Society. PMID: 20573916 [PubMed - as supplied by publisher] | | |
| N-isopropylacrylamide-based thermoresponsive polyelectrolyte multilayer films for human mesenchymal stem cell expansion.
June 25, 2010 at 6:19 AM
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| | N-isopropylacrylamide-based thermoresponsive polyelectrolyte multilayer films for human mesenchymal stem cell expansion. Biotechnol Prog. 2010 May 28; Authors: Liao T, Moussallem MD, Kim J, Schlenoff JB, Ma T Human mesenchymal stem cells (hMSCs) are colony-forming unit fibroblasts (CFU-F) derived from adult bone marrow and have significant potential for many cell-based tissue-engineering applications. Their therapeutic potential, however, is restricted by their diminishing plasticity as they are expanded in culture. In this study, we used N-isopropylacrylamide (NIPAM)-based thermoresponsive polyelectrolyte multilayer (N-PEMU) films as culture substrates to support hMSC expansion and evaluated their effects on cell properties. The N-PEMU films were made via layer-by-layer adsorption of thermoresponsive monomers copolymerized with charged monomers, positively charged allylamine hydrochloride (PAH), or negatively charged styrene sulfonic acid (PSS) and compared to fetal bovine serum (FBS) coated surfaces. Surface charges were shown to alter the extracellular matrix (ECM) structure and subsequently regulate hMSC responses including adhesion, proliferation, integrin expression, detachment, and colony forming ability. The positively charged thermal responsive surfaces improved cell adhesion and growth in a range comparable to control surfaces while maintaining significantly higher CFU-F forming ability. Immunostaining and Western blot results indicate that the improved cell adhesion and growth on the positively charged surfaces resulted from the elevated adhesion of ECM proteins such as fibronectin on the positively charge surfaces. These results demonstrate that the layer-by-layer approach is an efficient way to form PNIPAM-based thermal responsive surfaces for hMSC growth and removal without enzymatic treatment. The results also show that surface charge regulates ECM adhesion, which in turn influences not only cell adhesion but also CFU-forming ability and their multi-lineage differentiation potential. (c) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010. PMID: 20574992 [PubMed - as supplied by publisher] | | |
| Controlled nucleation of hydroxyapatite on alginate scaffolds for stem cell-based bone tissue engineering.
June 25, 2010 at 6:19 AM
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| | Controlled nucleation of hydroxyapatite on alginate scaffolds for stem cell-based bone tissue engineering. J Biomed Mater Res A. 2010 Jun 22; Authors: Suárez-González D, Barnhart K, Saito E, Vanderby R, Hollister SJ, Murphy WL Current bone tissue engineering strategies aim to grow a tissue similar to native bone by combining cells and biologically active molecules with a scaffold material. In this study, a macroporous scaffold made from the seaweed-derived polymer alginate was synthesized and mineralized for cell-based bone tissue engineering applications. Nucleation of a bone-like hydroxyapatite mineral was achieved by incubating the scaffold in modified simulated body fluids (mSBF) for 4 weeks. Analysis using scanning electron microscopy and energy dispersive x-ray analysis indicated growth of a continuous layer of mineral primarily composed of calcium and phosphorous. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue. In addition to the mineral characterization, the ability to control nucleation on the surface, into the bulk of the material, or on the inner pore surfaces of scaffolds was demonstrated. Finally, human MSCs attached and proliferated on the mineralized scaffolds and cell attachment improved when seeding cells on mineral coated alginate scaffolds. This novel alginate- HAP composite material could be used in bone tissue engineering as a scaffold material to deliver cells, and perhaps also biologically active molecules. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20574984 [PubMed - as supplied by publisher] | | |
| In vivo biodegradation and biocompatibility of PEG/sebacic acid-based hydrogels using a cage implant system.
June 25, 2010 at 6:19 AM
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| | In vivo biodegradation and biocompatibility of PEG/sebacic acid-based hydrogels using a cage implant system. J Biomed Mater Res A. 2010 Jun 22; Authors: Kim J, Dadsetan M, Ameenuddin S, Windebank AJ, Yaszemski MJ, Lu L Comprehensive in vivo biodegradability and biocompatibility of unmodified and Arg-Gly-Asp (RGD) peptide-modified PEG/sebacic acid-based hydrogels were evaluated and compared to the control material poly(lactide-co-glycolide) (PLGA) using a cage implantation system, as well as direct subcutaneous implantation for up to 12 weeks. The total weight loss after 12 weeks of implantation for unmodified PEGSDA and RGD-modified PEGSDA in the cage was approximately 42% and 52%, respectively, with no statistical difference (p > 0.05). The exudate analysis showed that PEGSDA hydrogels induced minimal inflammatory response up to 21 days following implantation, similar to the controls (empty cage and the cage containing PLGA discs). Histology analysis from direct subcutaneous implantation of the hydrogels and PLGA scaffold showed statistically similar resolution of the acute and chronic inflammatory responses with development of the fibrous capsule between the PEGSDA hydrogels and the control (PLGA). The cage system, as well as the histology analysis, demonstrated that the degradation products of both hydrogels, with or without RGD peptide modification, are biocompatible without statistically significant differences in the inflammatory responses, as compared to PLGA. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20574982 [PubMed - as supplied by publisher] | | |
| Electrospun micro/nanofibrous conduits composed of poly(epsilon-caprolactone) and small intestine submucosa powder for nerve tissue regeneration.
June 25, 2010 at 6:19 AM
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| | Electrospun micro/nanofibrous conduits composed of poly(epsilon-caprolactone) and small intestine submucosa powder for nerve tissue regeneration. J Biomed Mater Res B Appl Biomater. 2010 Jun 22; Authors: Hong S, Kim G Three-dimensional biocompatible and biodegradable scaffolds play important roles in tissue engineering. In this study, fibrous mats composed of electrospun poly(epsilon-caprolactone) (PCL)/small intestine submucosa (SIS) tubes were fabricated with a high degree of longitudinal alignment as a conduit for peripheral nerves. Fourier transform infrared analyses of electrospun PCL/SIS mats with various amounts of SIS showed that the SIS was well embedded within the PCL matrix. The diameter of the PCL/SIS fibers with the 3 wt % of SIS in the PCL solution decreased 40% relative to that of pure PCL fibers due to increased electrical conductivity and decreased surface tension. PCL/SIS (3 wt %) electrospun mats exhibited various synergistic effects, including stronger mechanical properties (Young's modulus = more than 80%) and enhanced hydrophilicity (water contact angle at 30 min = 54 degrees ) relative to pure PCL (water contact angle at 30 min = 142 degrees ). Cell attachment and proliferation experiments demonstrated that the interactions between nerve cells (PC-12) and the PCL/SIS conduits were more favorable than those between PC-12 cells and a pure PCL conduit. This study contributes to the understanding of the effects of including SIS in electrospun composite mats. The ability to fabricate highly aligned tubes of PCL/SIS with appropriate mechanical properties and cellular interactions shows great potential for the design of nerve regeneration conduits. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20574981 [PubMed - as supplied by publisher] | | |
| Novel polyurethanes with interconnected porous structure induce in vivo tissue remodeling and accompanied vascularization.
June 25, 2010 at 6:19 AM
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| | Novel polyurethanes with interconnected porous structure induce in vivo tissue remodeling and accompanied vascularization. J Biomed Mater Res A. 2010 Jun 22; Authors: Jovanovic D, Engels GE, Plantinga JA, Bruinsma M, van Oeveren W, Schouten AJ, van Luyn MJ, Harmsen MC Tissue engineering and regenerative medicine have furnished a vast range of modalities to treat either damaged tissue or loss of soft tissue or its function. In most approaches, a temporary porous scaffold is required to support tissue regeneration. The scaffold should be designed such that the turnover synchronizes with tissue remodeling and regeneration at the implant site. Segmented polyester urethanes (PUs) used in this study were based on epsilon-caprolactone (CL) and co-monomers D,L-lactide (D,L-L) and gamma-butyrolactone (BL), and 1,4-butanediisocyanate (BDI). In vitro, the PUs were nontoxic and haemocompatible. To test in vivo biocompatibility, the PUs were further processed into porous structures and subcutaneously implanted in rats for a period up to 21 days. Tissue remodeling and scaffold turnover was associated with a mild tissue response. The tissue response was characterized by extensive vascularization through the interconnected pores, with low numbers of macrophages on the edges and stroma formation inside the pores of the implants. The tissue ingrowth appeared to be related to the extent of microphase separation of the PUs and foam morphology. By day 21, all of the PU implants were highly vascularized, confirming the pores were interconnected. Degradation of P(CL/D,L-L)-PU was observed at this time, whereas the other two PU types remained intact. The robust method reported here of manufacturing and processing, good mechanical properties, and in vivo tissue response of the porous P(CL/D,L-L)-PU and PBCL-PU makes them excellent candidates as biomaterials with an application for soft tissue remodeling, for example, for cardiovascular regeneration. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20574980 [PubMed - as supplied by publisher] | | |
| Biological and mechanical properties of novel composites based on supramolecular polycaprolactone and functionalized hydroxyapatite.
June 25, 2010 at 6:19 AM
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| | Biological and mechanical properties of novel composites based on supramolecular polycaprolactone and functionalized hydroxyapatite. J Biomed Mater Res A. 2010 Jun 22; Authors: Shokrollahi P, Mirzadeh H, Scherman OA, Huck WT Supramolecular polymers based on quadruple hydrogen-bonding ureido-pyrimidinone (UPy) moieties hold promise as dynamic/stimuli-responsive materials in applications such as tissue engineering. Here, a new class of materials is introduced: supramolecular polymer composites. We show that despite the highly ordered structure and tacticity-dependent nature of hydrogen-bonded supramolecular polymers, the bioactivity of these polymers can be tuned through composite preparation with bioceramics. These novel supramolecular composites combine the superior processability of supramolecular polymers with the excellent bioactivity and mechanical characteristics of bioceramics. In particular, the bioactive composites prepared from supramolecular polycaprolactone and UPy-grafted hydroxyapatite (HApUPy) are described that can be easily formed into microporous biomaterials. The compression moduli increased about 40 and 90% upon composite preparation with HAp and HApUPy, respectively, as an indication to improved mechanical properties. These new materials show excellent potential as microporous composite scaffolds for the adhesion and proliferation of rat mesenchymal stem cells (rMSCs) as a first step toward bone regeneration studies; rMSCs proliferate about 2 and 2.7 times faster on the conventional composite with HAp and the supramolecular composite with (HApUPy) than on the neat PCL1250(UPy)(2). (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20574978 [PubMed - as supplied by publisher] | | |
| Composite nanofiber mats consisting of hydroxyapatite and titania for biomedical applications.
June 25, 2010 at 6:19 AM
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| | Composite nanofiber mats consisting of hydroxyapatite and titania for biomedical applications. J Biomed Mater Res B Appl Biomater. 2010 Jun 22; Authors: Kim HM, Chae WP, Chang KW, Chun S, Kim S, Jeong Y, Kang IK Composite nanofiber mats (HA/TiO(2)) consisting of hydroxyapatite (HA) and titania (TiO(2)) were fabricated via an electrospinning technique and then collagen (type I) was immobilized on the surface of the HA/TiO(2) composite nanofiber mat to improve tissue compatibility. The structure and morphology of the collagen-immobilized composite nanofiber mat (HA/TiO(2)-col) was investigated using an X-ray diffractometer, electron spectroscopy for chemical analysis, and scanning electron microscope. The potential of the HA/TiO(2)-col composite nanofiber mat for use as a bone scaffold was assessed by an experiment with osteoblastic cells (MC3T3-E1) in terms of cell adhesion, proliferation, and differentiation. The results showed that the HA/TiO(2)-col composite nanofiber mats possess better cell adhesion and significantly higher proliferation and differentiation than untreated HA/TiO(2) composite nanofiber mats. This result suggests that the HA/TiO(2)-col composite nanofiber mat has a high-potential for use in the field of bone regeneration and tissue engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20574975 [PubMed - as supplied by publisher] | | |
| Engineering Liver Tissues Under The Kidney Capsule Site Provides Therapeutic Effects to Hemophilia B Mice.
June 25, 2010 at 6:19 AM
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| | Engineering Liver Tissues Under The Kidney Capsule Site Provides Therapeutic Effects to Hemophilia B Mice. Cell Transplant. 2010 Jun 23; Authors: Ohashi K, Tatsumi K, Utoh R, Takagi S, Shima M, Okano T Recent advances in liver tissue engineering have encouraged further investigation into the evaluation of therapeutic benefits based on animal disease models. In the present study, liver tissues were engineered in the coagulation factor IX knockout (FIX-KO) mice, a mouse model of hemophilia B, to determine if the tissue engineering approach would provide therapeutic benefits. Primary hepatocytes were isolated from the liver of wild type mice and suspended in a mixture of culture medium and extracellular matrix components. The hepatocyte suspension was injected into the space under the bilateral kidney capsules of the FIX-KO mice to engineer liver tissues. The plasma FIX activities (FIX:C) of the untreated FIX-KO mice were undetectable at any time point. In contrast, the liver tissue engineered FIX-KO mice achieved 1.5 to 2.5% of plasma FIX activities (FIX:C) and this elevated FIX:C level persisted throughout the 90 day experimental period. Significant FIX mRNA expression levels were found in the engineered liver tissues at levels similar to the wild type livers. The present study demonstrates that liver tissue engineering could provide therapeutic benefits in the treatment of hemophilia B. PMID: 20573301 [PubMed - as supplied by publisher] | | |
| Levels of specific immunoglobulin G to the forsythia detaching factor of Tannerella forsythia in gingival crevicular fluid are related to the periodontal status.
June 25, 2010 at 6:19 AM
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| | Levels of specific immunoglobulin G to the forsythia detaching factor of Tannerella forsythia in gingival crevicular fluid are related to the periodontal status. J Periodontal Res. 2010 Jun 20; Authors: Onishi H, Arakawa S, Nakajima T, Izumi Y Onishi H, Arakawa S, Nakajima T, Izumi Y. Levels of specific immunoglobulin G to the forsythia detaching factor of Tannerella forsythia in gingival crevicular fluid are related to the periodontal status. J Periodont Res 2010; doi: 10.1111/j.1600-0765.2010.01283.x. (c) 2010 John Wiley & Sons A/S Background and Objective: Forsythia detaching factor (FDF) is a putative virulence factor of Tannerella forsythia that induces detachment of adherent cells and interleukin-8 production in human fibroblasts. The objective of the present study was to clarify the relationship between anti-FDF IgG levels in gingival crevicular fluid and the clinical status in patients with periodontitis and in healthy subjects. Material and Methods: Gingival crevicular fluid and subgingival plaque samples were obtained from both the diseased and healthy sites of 37 patients with periodontitis and from 30 healthy subjects. Anti-FDF IgG levels were evaluated, and both the fdf gene and T. forsythia 16S ribosomal RNA (rRNA) were detected using the PCR. Results: Anti-FDF IgG levels (of both diseased and healthy sites) of patients with periodontitis were significantly higher than those of healthy subjects. Among the patients with periodontitis, anti-FDF IgG levels of healthy sites were significantly higher than those of diseased sites and the levels showed negative correlations with probing pocket depth and clinical attachment level. Among the patients with periodontitis, T. forsythia 16S rRNA was detected in 18 of 37 diseased sites and in 5 of 29 healthy sites, and the fdf gene was detected in 19 of 37 diseased sites and in 7 of 29 healthy sites. By contrast, no healthy subjects were positive for T. forsythia 16S rRNA or the fdf gene. Conclusion: These data suggest that anti-FDF IgG levels in gingival crevicular fluid are related to the periodontal status. PMID: 20572920 [PubMed - as supplied by publisher] | | |
| Novel polyurethanes with interconnected porous structure induce in vivo tissue remodeling and accompanied vascularization.
June 25, 2010 at 6:01 AM
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| | Novel polyurethanes with interconnected porous structure induce in vivo tissue remodeling and accompanied vascularization. J Biomed Mater Res A. 2010 Jun 22; Authors: Jovanovic D, Engels GE, Plantinga JA, Bruinsma M, van Oeveren W, Schouten AJ, van Luyn MJ, Harmsen MC Tissue engineering and regenerative medicine have furnished a vast range of modalities to treat either damaged tissue or loss of soft tissue or its function. In most approaches, a temporary porous scaffold is required to support tissue regeneration. The scaffold should be designed such that the turnover synchronizes with tissue remodeling and regeneration at the implant site. Segmented polyester urethanes (PUs) used in this study were based on epsilon-caprolactone (CL) and co-monomers D,L-lactide (D,L-L) and gamma-butyrolactone (BL), and 1,4-butanediisocyanate (BDI). In vitro, the PUs were nontoxic and haemocompatible. To test in vivo biocompatibility, the PUs were further processed into porous structures and subcutaneously implanted in rats for a period up to 21 days. Tissue remodeling and scaffold turnover was associated with a mild tissue response. The tissue response was characterized by extensive vascularization through the interconnected pores, with low numbers of macrophages on the edges and stroma formation inside the pores of the implants. The tissue ingrowth appeared to be related to the extent of microphase separation of the PUs and foam morphology. By day 21, all of the PU implants were highly vascularized, confirming the pores were interconnected. Degradation of P(CL/D,L-L)-PU was observed at this time, whereas the other two PU types remained intact. The robust method reported here of manufacturing and processing, good mechanical properties, and in vivo tissue response of the porous P(CL/D,L-L)-PU and PBCL-PU makes them excellent candidates as biomaterials with an application for soft tissue remodeling, for example, for cardiovascular regeneration. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20574980 [PubMed - as supplied by publisher] | | |
| Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration.
June 25, 2010 at 6:01 AM
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| | Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration. N Engl J Med. 2010 Jun 23; Authors: Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G BACKGROUND: Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal stem-cell deficiency. We investigated the long-term clinical results of cell therapy in patients with burn-related corneal destruction associated with limbal stem-cell deficiency, a highly disabling ocular disease. METHODS: We used autologous limbal stem cells cultivated on fibrin to treat 112 patients with corneal damage, most of whom had burn-dependent limbal stem-cell deficiency. Clinical results were assessed by means of Kaplan-Meier, Kruskal-Wallis, and univariate and multivariate logistic-regression analyses. We also assessed the clinical outcome according to the percentage of holoclone-forming stem cells, detected as cells that stain intensely (p63-bright cells) in the cultures. RESULTS: Permanent restoration of a transparent, renewing corneal epithelium was attained in 76.6% of eyes. The failures occurred within the first year. Restored eyes remained stable over time, with up to 10 years of follow-up (mean, 2.91+/-1.99; median, 1.93). In post hoc analyses, success - that is, the generation of normal epithelium on donor stroma - was associated with the percentage of p63-bright holoclone-forming stem cells in culture. Cultures in which p63-bright cells constituted more than 3% of the total number of clonogenic cells were associated with successful transplantation in 78% of patients. In contrast, cultures in which such cells made up 3% or less of the total number of cells were associated with successful transplantation in only 11% of patients. Graft failure was also associated with the type of initial ocular damage and postoperative complications. CONCLUSIONS: Cultures of limbal stem cells represent a source of cells for transplantation in the treatment of destruction of the human cornea due to burns. Copyright 2010 Massachusetts Medical Society. PMID: 20573916 [PubMed - as supplied by publisher] | | |
| Photo-aging: a literature review.
June 25, 2010 at 6:01 AM
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| | Photo-aging: a literature review. J Med Assoc Thai. 2010 Jun;93(6):753-7 Authors: Limpiangkanan W, Limpiangkanan W The average age of people has been increasing over the years, triggering more awareness and more interest in the study of regenerative medicine, especially degeneration of the skin which is an organ that is crucial noticeably for appearance. Skin aging is the multifactorial process both internal and external factors, such as, age, sex, race, disease of internal organs and environmental exposure. However, the main causes of skin degeneration are heredity and sunlight. The latter induces the most skin degeneration. Due to strong sunlight all year round in the tropical zone, serious skin degeneration has an effect on Thai people, causing both anatomical change and microscopic change. Thus far, many studies have been conducted on pathogenesis and prevention of Photo-aging, as well as regeneration of damaged skin. The current article helps make further progress to these issues. PMID: 20572384 [PubMed - in process] | | | | 
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