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| Human stem cells and drug screening: opportunities and challenges.
March 27, 2010 at 8:28 AM
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| | Human stem cells and drug screening: opportunities and challenges. Nat Rev Drug Discov. 2010 Mar 26; Authors: Ebert AD, Svendsen CN High-throughput screening technologies are widely used in the early stages of drug discovery to rapidly evaluate the properties of thousands of compounds. However, they generally rely on testing compound libraries on highly proliferative immortalized or cancerous cell lines, which do not necessarily provide an accurate indication of the effects of compounds in normal human cells or the specific cell type under study. Recent advances in stem cell technology have the potential to allow production of a virtually limitless supply of normal human cells that can be differentiated into any specific cell type. Moreover, using induced pluripotent stem cell technology, they can also be generated from patients with specific disease traits, enabling more relevant modelling and drug screens. This article discusses the opportunities and challenges for the use of stem cells in drug screening with a focus on induced pluripotent stem cells. PMID: 20339370 [PubMed - as supplied by publisher] | | |
| Current investigations into carbon nanotubes for biomedical application.
March 27, 2010 at 8:28 AM
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| | Current investigations into carbon nanotubes for biomedical application. Biomed Mater. 2010 Mar 25;5(2):22001 Authors: Li X, Fan Y, Watari F The nano-dimensionality of nature has logically given rise to the interest in using nanomaterials in the biomedical field. Currently, a lot of investigations into carbon nanotubes (CNTs), as one of the typical nanomaterials, are being made for biomedical application. In this review, five parts, such as cellular functions induced by CNTs, apatite formation on CNTs, CNT-based tissue engineering scaffold, functionalized CNTs for the delivery of genes and drugs and CNT-based biosensors, are stated, which might indicate that CNTs, with a range of unique properties, appear suited as a biomaterial and may become a useful tool for tissue engineering. However, everything has two parts and CNTs is not an exception. There are still concerns about cytotoxicity and biodegradation of CNTs. Chemical fictionalization may be one of the effective ways to improve the 'disadvantages' and utilize the 'advantages' of CNTs. One of their 'disadvantages', unbiodegradable property, may be ! utilized by creating monitors in in vivo-engineered tissues or nanosized CNT-based biosensors. Other promising research points, for example proteins adsorbed on CNTs, use of CNTs in combination with other biomaterials to achieve the goals of tissue engineering, mineralization of CNTs and standard toxicological tests for CNTs, are also described in the conclusion and perspectives part. PMID: 20339169 [PubMed - as supplied by publisher] | | |
| Modularly assembled porous cell-laden hydrogels.
March 27, 2010 at 8:28 AM
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| | Modularly assembled porous cell-laden hydrogels. Biomaterials. 2010 Mar 23; Authors: Liu B, Liu Y, Lewis AK, Shen W Porous cell-laden hydrogels have been modularly assembled to address the challenges in 3-dimensional tissue engineering. Microgels photolithographically fabricated from solutions of poly(ethylene glycol) diacrylate are assembled into large porous constructs in the presence of a polypeptide-based, physically bonded cross-linker. The assembly occurs through a physiologically permissive Michael-type addition reaction between the acrylate groups on the surface of the microgels and the thiol groups on the cross-linker. The constructs assembled from star-shaped microgels exhibit higher porosity, permeability, and pore interconnectivity than those formed from circle- and square-shaped microgels. The correlation between the properties of assembled constructs and the morphological features of microgels suggests the possibility for bottom-up modulation of the construct properties. The high pore interconnectivity revealed on the level of individual microgels suggests that th! ese constructs are suitable for tissue engineering. Cells remain viable inside centimeter-sized constructs when cultured under perfusion. These constructs have the combined advantages of preformed porous scaffolds and in situ forming hydrogels in allowing enhanced mass transfer, uniform cell seeding, and protection of cells from excessive, non-physiological shear stress. Large constructs can be assembled in one step and have no limitations in size. This method will provide opportunities to create large 3-dimensional tissue engineered products. PMID: 20338634 [PubMed - as supplied by publisher] | | |
| Analyzing Polyaniline-poly(2-acrylamido-2-methylpropane sulfonic acid) Biocompatibility with 3T3 Fibroblasts.
March 27, 2010 at 8:28 AM
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| | Analyzing Polyaniline-poly(2-acrylamido-2-methylpropane sulfonic acid) Biocompatibility with 3T3 Fibroblasts. J Biomater Sci Polym Ed. 2010;21(5):623-34 Authors: Bayer CL, Trenchard IJ, Peppas NA Conductive polymers can be utilized as unique functional elements in future intelligent biomaterials required for tissue engineering, cell stimulation and drug delivery. Research in these areas could be limited by established methods of conductive polymer synthesis which do not provide an easy route towards large scale processing of these materials. Typically, conductive polymers are highly insoluble in biocompatible solvents, and can be mechanically brittle, making their integration with biomaterials challenging. As an alternative, the use of a water-soluble conductive polymer for integration with biomaterials, a polyaniline template synthesized with poly(2-acrylamido-2-methylpropanesulfonic acid) (PANI-PAAMPSA), is proposed. To address key fundamental questions about the biocompatibility of this conductive polymer, cell cytotoxicity and proliferation assays have been performed on NIH 3T3 fibroblasts cultured on films of PANI-PAAMPSA. It was determined that the c! ell cultures maintained growth habits similar to those cultured on the control surfaces. Additionally, conductivity of the PANI-PAAMPSA films subsequent to exposure to the cell culture was demonstrated, indicating the materials retain functionality after cell growth. These results indicate that this type of template synthesized PANI could be successfully implemented as a functional, conductive biomaterial. PMID: 20338096 [PubMed - in process] | | |
| In Vitro Proliferation and Chondrogenic Differentiation of Rat Bone Marrow Stem Cells Cultured with Gelatin Hydrogel Microspheres for TGF-beta1 Release.
March 27, 2010 at 8:28 AM
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| | In Vitro Proliferation and Chondrogenic Differentiation of Rat Bone Marrow Stem Cells Cultured with Gelatin Hydrogel Microspheres for TGF-beta1 Release. J Biomater Sci Polym Ed. 2010;21(5):609-21 Authors: Ogawa T, Akazawa T, Tabata Y The objective of this study was to evaluate the proliferation and chondrogenic differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) cultured with gelatin hydrogel microspheres of cell scaffold which can release transforming growth factor-beta1 (TGF-beta1). Gelatin was dehydrothermally cross-linked in different conditions in a water-in-oil emulsion state to obtain gelatin hydrogel microspheres with different water content. The microspheres functioned not only as the scaffold of MSC, but also the carrier matrix of TGF-beta1 release. The MSC proliferation depended on the water content of microspheres. Higher MSC proliferation was observed for the gelatin microspheres with lower water content. When cultured with the gelatin hydrogel microspheres, MSC formed their aggregates, in contrast to culturing with hydrogel sheets. The cell viability was significantly high compared with that of the hydrogel sheet. The production of sulfated glycosaminaglycan ! (sGAG) from MSC was examined as a measure of chondrogenic differentiation, after their culturing in a normal and chondrogenic differentiation media. For both the cultures, the amount of sGAG produced was significantly higher for MSC cultured with the gelatin microspheres than that of the gelatin sheet. Stronger differentiation of MSC was achieved in culture with the microspheres incorporating TGF-beta1 than that of MSC cultured in the medium containing the same amount of TGF-beta1. It is concluded that the gelatin hydrogel microspheres function well as both the scaffold of MSC and the matrix of TGF-beta1 release, resulting in enhanced MSC aggregation and the consequent promotion of cell proliferation and differentiation. PMID: 20338095 [PubMed - in process] | | |
| The Effect of Hybridization of Hydrogels and Poly(L-lactide-co-epsilon-caprolactone) Scaffolds on Cartilage Tissue Engineering.
March 27, 2010 at 8:28 AM
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| | The Effect of Hybridization of Hydrogels and Poly(L-lactide-co-epsilon-caprolactone) Scaffolds on Cartilage Tissue Engineering. J Biomater Sci Polym Ed. 2010;21(5):581-92 Authors: Jung Y, Kim SH, Kim YH, Kim SH For repairing cartilage defects by cartilage tissue engineering, it is important that engineered cartilage that is fabricated with scaffolds and cells can maintain the biological and physiological functions of cartilage, and also can induce three-dimensional spatial organization of chondrocytes. In this sense, hydrogels such as fibrin gels (FG) and hyaluronan (HA) are widely used for application in cartilage treatment. However, the use of hydrogels alone as a scaffold has a physical weakness; the mechanical properties of hydrogels are too weak to endure complex loading in the body. In this study, for mimicking a native cartilage microenvironment, we made cell-hybrid scaffold constructs with poly(L-lactide-co-epsilon-caprolactone) (PLCL) scaffolds and hydrogels to guide three-dimensional spatial organization of cells and extracellular matrix. A highly elastic scaffold was fabricated from PLCL with 85% porosity and 300-500 mum pore size using a gel-pressing method. ! The mixture of rabbit chondrocytes and hydrogels was seeded on PLCL scaffolds, and was subcutaneously implanted into nude mice for up to eight weeks. The cell seeding efficiency of the hybrid scaffolds with FG or HA was higher than that of the PLCL scaffolds. From in vivo studies, the accumulation of cartilaginous extracellular matrices of constructs, which was increased by hybridization of hydrogels and PLCL scaffolds, showed that the cell-hybrid scaffold constructs formed mature and well-developed cartilaginous tissue. In conclusion, the hybridization of hydrogels and PLCL scaffold for three-dimensional spatial organization of cells would provide a biomimetic environment where cartilage tissue growth is enhanced and facilitated. It can enhance the production of cartilaginous extracellular matrices and, consequently, improve the quality of the cartilaginous tissue formed. PMID: 20338093 [PubMed - in process] | | |
| Argon-plasma-treated chitosan: surface characterization and initial attachment of osteoblasts.
March 27, 2010 at 8:28 AM
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| | Argon-plasma-treated chitosan: surface characterization and initial attachment of osteoblasts. J Biomater Sci Polym Ed. 2010;21(5):563-79 Authors: Wu YC, Lee TM, Lin JC, Shaw SY, Yang CY Chitosan is a biocompatible, biodegradable and non-toxic material. It is also an advanced material used for wound dressings, drug and gene delivery, and tissue engineering. In this study, we treated chitosan film with argon plasma and characterized both its physical and chemical properties. We found that argon plasma increased nano-scale roughness and introduced a carbonyl group to the chitosan surface. Meanwhile, the contact angles also decreased as the duration of the plasma treatment on chitosan was prolonged, indicating that the increased roughness and carbonyl group promote the hydrophilicity of the chitosan film surface. Moreover, the number of osteoblasts adhering to chitosan films increased and their morphology became flatter with longer plasma treatments. In conclusion, this study first demonstrates that plasma treatment on chitosan exerting surface-property change is capable of triggering the initial attachment of osteoblasts to chitosan surfaces. PMID: 20338092 [PubMed - in process] | | |
| Small hairpin RNA interference of the Nogo receptor inhibits oxygen-glucose deprivation-induced damage in rat hippocampal slice cultures.
March 27, 2010 at 8:28 AM
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| | Small hairpin RNA interference of the Nogo receptor inhibits oxygen-glucose deprivation-induced damage in rat hippocampal slice cultures. Neuropathology. 2010 Mar 10; Authors: Peng Y, Zhang QL, Xu D, Wang YP, Qin XY In adult mammals, CNS damage does not repair well spontaneously. The Nogo receptor (NgR) signaling pathway prevents axonal regrowth and promotes neuronal apoptosis. This pathway, and pathways like it, may be part of the reason why nerves do not regrow. A number of preclinical experiments inhibiting portions of the NgR pathway have yielded limited induction of nerve repair. Here, we developed a small hairpin RNA (shRNA) to knock down NgR expression. With the use of rat hippocampal slices in tissue culture, we induced neuronal damage similar to that of ischemia-reperfusion injury by exposing the cultured tissues to oxygen-glucose deprivation. We then assayed the effect of NgR knockdown in this model system. Adenovirally delivered NgR shRNA decreased NgR mRNA and protein expression. Thirty minutes of oxygen-glucose deprivation resulted in widespread tissue damage, including apoptosis and loss of neurite extension, 72 h after termination of oxygen-glucose deprivation.! The NgR shRNA knockdown reduced, but did not eliminate, the effects of oxygen-glucose deprivation. Thus, NgR shRNA shows promise as a potential tool for the treatment of nerve damage. PMID: 20337950 [PubMed - as supplied by publisher] | | |
| [Experiment of oral mucosa epithelial cells cultured on small intestinal submucosa in vitro]
March 27, 2010 at 8:28 AM
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| | [Experiment of oral mucosa epithelial cells cultured on small intestinal submucosa in vitro] Hua Xi Kou Qiang Yi Xue Za Zhi. 2010 Feb;28(1):76-80 Authors: Tan B, Wei RQ, Yang ZM, Li XQ, Han P, Zhi W, Xie HQ, Ren Y, Tan ZX OBJECTIVE: To explore an effective method to culture oral mucosa epithelial cells (OMECs) of canine in vitro, and to observe the biological characteristics of OMECs growing on small intestinal submucosa (SIS) in order to provide the experimental basis for epithelium tissue engineering. METHODS: The primary OMECs were cultivated with DKSFM (defined keratinocyte serum free medium) containing 6% fetal bovine serum (FBS). The morphological characteristics and the growth curve of OMECs were observed. The expressions of OMECs marker (CK19) were examined by immunocytochemistry. The 2nd passage of OMECs were seeded on SIS, OMECs co-cultured with SIS were observed by hematoxylin-eosin staining, immunohistochemical staining, and scanning electron microscope (SEM). RESULTS: OMECs were grown well in DKSFM. Immunohistochemical staining of the 2nd passage cultured canine OMECs with broadly reacting anti-cytokeratin anyibodies (CK19) was positive. OMECs formed a single layer on ! the surface of SIS, and eight days later the cells were polygong and arranged like slabstone. CONCLUSION: Culture of canine OMECs in DKSFM containing 6% FBS is a simple and feasible method. SIS has good biocompatibility, it is a kind of good bioscafold in the tissue-engineered epithelium. PMID: 20337083 [PubMed - in process] | | |
| [Application of poly (N-isopropylacrylamide) and its derivatives in tissue engineering]
March 27, 2010 at 8:28 AM
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| | [Application of poly (N-isopropylacrylamide) and its derivatives in tissue engineering] Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2010 Feb;27(1):206-10 Authors: Wang X, Luo H, Guan Y Poly-N-isopropylacrylamide (PNIPAAm) is a new kind of intelligent material. It shows favorable thermo sensitivity because of the structure of hydrophilic acrylamino and hydrophobic isopropyl. PNIPAAm also shows good biocompatibility and non-toxicity. All the characters as above make it an ideal extra cellular matrix material for tissue engineering. This paper reviews its application in tissue engineering. PMID: 20337055 [PubMed - in process] | | |
| Glottal reconstruction with a tissue engineering technique using polypropylene mesh: a canine experiment.
March 27, 2010 at 8:28 AM
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| | Glottal reconstruction with a tissue engineering technique using polypropylene mesh: a canine experiment. Ann Otol Rhinol Laryngol. 2010 Feb;119(2):110-7 Authors: Yamashita M, Kanemaru S, Hirano S, Umeda H, Kitani Y, Omori K, Nakamura T, Ito J OBJECTIVES: The larynx must be resected in some cases of cancer or stenosis, and various techniques are generally employed to fill the resulting defect. No ideal way, however, has been established to restore vocal function after this form of insult. The aim of this preliminary feasibility study in a canine model was to investigate the effectiveness of a polypropylene-based tissue engineering approach to repair a partial glottal defect. METHODS: Eight dogs were used in this study. A laryngeal defect involving resection of the left vocal fold was created through a thyroid cartilage window. A scaffold made of polypropylene and collagen was preclotted and wrapped with autologous fascia lata, inserted through the window, and sutured to the laryngeal defect in 5 dogs. The defect was reconstructed with an adjacent sternohyoid muscle flap in 3 control dogs. The surgical site was evaluated 3 months after operation by fiberscopic examination, computed tomographic imaging, h! istologic evaluation, and study of excised larynges. RESULTS: On fiberscopic examination, the experimental group implants were completely covered with regenerated mucosa in all cases, and a favorable vocal fold contour was found in 4 of the 5 cases. One case was characterized by a concave vocal fold shape and red granulation. In the control group, the muscle flap was replaced by scarred mucosa with a concave vocal fold contour in 2 cases, and there was soft white granulation at the anterior resected edge in the third case. The histologic data revealed the regeneration of lined epithelium, subepithelial tissue, and muscle structure in both groups. The excised larynx phonatory data revealed reduced vibratory amplitude in the experimental group compared with the control group; however, excised phonation was not achieved in 2 of the 3 cases in the control group. CONCLUSIONS: This polypropylene-based tissue engineering technique appears to be a viable tool for glottal reconstruc! tion; however, additional refinement is required to maximize l! ong-term phonatory function. PMID: 20336922 [PubMed - in process] | | |
| Rem2 GTPase maintains survival of human embryonic stem cells as well as enhancing reprogramming by regulating p53 and cyclin D1.
March 27, 2010 at 8:28 AM
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| | Rem2 GTPase maintains survival of human embryonic stem cells as well as enhancing reprogramming by regulating p53 and cyclin D1. Genes Dev. 2010 Mar 15;24(6):561-73 Authors: Edel MJ, Menchon C, Menendez S, Consiglio A, Raya A, Izpisua Belmonte JC Human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have the unique abilities of differentiation into any cell type of the organism (pluripotency) and indefinite self-renewal. Here, we show that the Rem2 GTPase, a suppressor of the p53 pathway, is up-regulated in hESCs and, by loss- and gain-of-function studies, that it is a major player in the maintenance of hESC self-renewal and pluripotency. We show that Rem2 mediates the fibroblastic growth factor 2 (FGF2) signaling pathway to maintain proliferation of hESCs. We demonstrate that Rem2 effects are mediated by suppressing the transcriptional activity of p53 and cyclin D(1) to maintain survival of hESCs. Importantly, Rem2 does this by preventing protein degradation during DNA damage. Given that Rem2 maintains hESCs, we also show that it is as efficient as c-Myc by enhancing reprogramming of human somatic cells into iPSCs eightfold. Rem2 does this by accele! rating the cell cycle and protecting from apoptosis via its effects on cyclin D(1) expression/localization and suppression of p53 transcription. We show that the effects of Rem2 on cyclin D(1) are independent of p53 function. These results define the cell cycle and apoptosis as a rate-limiting step during the reprogramming phenomena. Our studies highlight the possibility of reprogramming somatic cells by imposing hESC-specific cell cycle features for making safer iPSCs for cell therapy use. PMID: 20231315 [PubMed - indexed for MEDLINE] | | |
| Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival.
March 27, 2010 at 8:28 AM
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| | Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1124-9 Authors: Gjerdrum C, Tiron C, Høiby T, Stefansson I, Haugen H, Sandal T, Collett K, Li S, McCormack E, Gjertsen BT, Micklem DR, Akslen LA, Glackin C, Lorens JB Metastasis underlies the majority of cancer-related deaths. Thus, furthering our understanding of the molecular mechanisms that enable tumor cell dissemination is a vital health issue. Epithelial-to-mesenchymal transitions (EMTs) endow carcinoma cells with enhanced migratory and survival attributes that facilitate malignant progression. Characterization of EMT effectors is likely to yield new insights into metastasis and novel avenues for treatment. We show that the presence of the receptor tyrosine kinase Axl in primary breast cancers independently predicts strongly reduced overall patient survival, and that matched patient metastatic lesions show enhanced Axl expression. We demonstrate that Axl is strongly induced by EMT in immortalized mammary epithelial cells that establishes an autocrine signaling loop with its ligand, Gas6. Epiallelic RNA interference analysis in metastatic breast cancer cells delineated a distinct threshold of Axl expression for mesenchymal! -like in vitro cell invasiveness and formation of tumors in foreign and tissue-engineered microenvironments in vivo. Importantly, in two different optical imaging-based experimental breast cancer models, Axl knockdown completely prevented the spread of highly metastatic breast carcinoma cells from the mammary gland to lymph nodes and several major organs and increased overall survival. These findings suggest that Axl represents a downstream effector of the tumor cell EMT that is required for breast cancer metastasis. Thus, the detection and targeted treatment of Axl-expressing tumors represents an important new therapeutic strategy for breast cancer. PMID: 20080645 [PubMed - indexed for MEDLINE] | | |
| Forever young: how to control the elongation, differentiation, and proliferation of cells using nanotechnology.
March 27, 2010 at 8:28 AM
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| | Forever young: how to control the elongation, differentiation, and proliferation of cells using nanotechnology. Cell Transplant. 2009;18(9):1047-58 Authors: Ellis-Behnke RG, Liang YX, Guo J, Tay DK, Schneider GE, Teather LA, Wu W, So KF Within the emerging field of stem cells there is a need for an environment that can regulate cell activity, to slow down differentiation or proliferation, in vitro or in vivo while remaining invisible to the immune system. By creating a nanoenvironment surrounding PC12 cells, Schwann cells, and neural precursor cells (NPCs), we were able to control the proliferation, elongation, differentiation, and maturation in vitro. We extended the method, using self-assembling nanofiber scaffold (SAPNS), to living animals with implants in the brain and spinal cord. Here we show that when cells are placed in a defined system we can delay their proliferation, differentiation, and maturation depending on the density of the cell population, density of the matrix, and the local environment. A combination of SAPNS and young cells can be implanted into the central nervous system (CNS), eliminating the need for immunosuppressants. PMID: 20040141 [PubMed - indexed for MEDLINE] | | |
| Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells.
March 27, 2010 at 8:28 AM
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| | Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells. Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1408-14 Authors: Gomes JA, Geraldes Monteiro B, Melo GB, Smith RL, Cavenaghi Pereira da Silva M, Lizier NF, Kerkis A, Cerruti H, Kerkis I PURPOSE: To determine the outcome of the use of a tissue-engineered cell sheet composed of human undifferentiated immature dental pulp stem cells (hIDPSC) for ocular surface reconstruction in an animal model of total limbal stem cell deficiency (LSCD). METHODS: LSCD was induced by the application of 0.5 M NaOH to the right eye of rabbits for 25 seconds (mild chemical burn [MCB]) and for 45 seconds (severe chemical burn [SCB]). After 1 month, a superficial keratectomy was performed to remove the fibrovascular pannus that covered the animals' burned corneas. A tissue-engineered hIDPSC sheet was transplanted onto the corneal bed and then covered with deepithelialized human amniotic membrane (AM). In the respective control groups, the denuded cornea was covered with AM only. After 3 months, a detailed analysis of the rabbit eyes was performed with regard to clinical aspect, histology, electron microscopy, and immunohistochemistry. RESULTS: Corneal transparency of the ! rabbit eyes that underwent hIDPSC transplantation was improved throughout the follow-up, while the control corneas developed total conjunctivalization and opacification. Rabbits from the MCB group showed clearer corneas with less neovascularization. The clinical data were confirmed by histologic analysis that showed healthy uniform corneal epithelium, especially in the MCB group. The presence of hIDPSC was detected using an anti-hIDPSC antibody. The corneal tissue also showed positive immunostaining with anti-human antibodies. In the control corneas, none of these antigens were detected. CONCLUSIONS: Overall, these data showed that transplantation of a tissue-engineered hIDPSC sheet was successful for the reconstruction of corneal epithelium in an animal model of LSCD. PMID: 19892864 [PubMed - indexed for MEDLINE] | | |
| Nano to the meso scale: influence on cell transplantation.
March 27, 2010 at 8:28 AM
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| | Nano to the meso scale: influence on cell transplantation. Discov Med. 2006 Dec;6(36):234-8 Authors: Halberstadt C, Emerich DF, Gonsalves K The success of organ transplantation is one of medicine's finest accomplishments. Ironically, this same success has led to a dilemma in that there are simply too few donor organs available to treat the millions of patients that would benefit from their procurement and transplantation. The answer(s) to this shortage will likely come from transplanting specific cells, i.e., cell transplantation, tailored to replace equally specific functions normally served by damaged tissues or organs. To facilitate successful clinical outcomes, technologies derived from areas such as nanoscience will play a more prominent role and will be discussed in this review. PMID: 17250789 [PubMed - indexed for MEDLINE] | | | | 
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