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| Challenges in using stem cells for cardiac repair.
April 16, 2010 at 8:04 AM
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| | Challenges in using stem cells for cardiac repair. Sci Transl Med. 2010 Apr 14;2(27):27ps17 Authors: Mummery CL, Davis RP, Krieger JE Of the many diseases discussed in the context of stem cell therapy, those concerning the heart account for almost one-third of the publications in the field. However, the long-term clinical outcomes have been disappointing, in part because of preclinical studies failing to optimize the timing, number, type, and method of cell delivery and to account for shape changes that the heart undergoes during failure. In situations in which cardiomyocytes have been used in cell therapy, their alignment and integration with host tissue have not been realized. Here we review the present status of direct delivery of stem cells or their derivative cardiomyocytes to the heart and the particular challenges each cell type brings, and consider where we should go from here. PMID: 20393186 [PubMed - in process] | | |
| AID in reprogramming: Quick and efficient: identification of a key enzyme called AID, and its activity in DNA demethylation, may help to overcome a pivotal epigenetic barrier in reprogramming somatic cells toward pluripotency.
April 16, 2010 at 6:14 AM
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| | AID in reprogramming: Quick and efficient: identification of a key enzyme called AID, and its activity in DNA demethylation, may help to overcome a pivotal epigenetic barrier in reprogramming somatic cells toward pluripotency. Bioessays. 2010 Apr 9; Authors: Deng W Current methods of reprogramming differentiated cells into induced pluripotent stem cells remain slow and inefficient. In a recent report published online in Nature, Bhutani et al.1 developed a cell fusion strategy, achieving quick and efficient reprogramming toward pluripotency. Using this assay, they identified an immune system protein called activation-induced cytidine deaminase, or AID, which unexpectedly is actually able to "aid" in reprogramming due to its involvement in DNA demethylation that is required for induction of the two key pluripotency genes, Oct4 and Nanog. More recently, Popp et al. 2 also reported online in Nature that AID is important for complete cell reprogramming in mammals. Together, these findings provide new insights into how cells are reprogrammed, identify the specific role of AID in cell fate reversal, and advance the field of regenerative medicine. PMID: 20394066 [PubMed - as supplied by publisher] | | |
| iPS cell technology in regenerative medicine.
April 16, 2010 at 6:14 AM
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| | iPS cell technology in regenerative medicine. Ann N Y Acad Sci. 2010 Mar;1192(1):38-44 Authors: Lengner CJ The promise of treating human genetic and degenerative diseases through the application of pluripotent cell-based tissue engineering and regenerative medicine has come significantly closer to realization since the isolation of human embryonic stem (ES) cells. While the study of ES cells has greatly increased our fundamental understanding of pluripotency, technical and ethical limitations have been seemingly insurmountable impediments to the application of these cells in the clinic. The recent discovery that somatic mammalian cells can be epigenetically reprogrammed to a pluripotent state through the exogenous expression of the transcription factors OCT4, SOX2, KLF4, and c-MYC has yielded a new cell type for potential application in regenerative medicine, the induced pluripotent stem (iPS) cell. Here we discuss how advances in iPS cell technology have led to the generation of patient-specific cell lines that can potentially be used to model human diseases and ultim! ately act as therapeutic agents. PMID: 20392216 [PubMed - in process] | | |
| Fabrication of three-dimensional scaffolds for heterogeneous tissue engineering.
April 16, 2010 at 6:11 AM
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| | Fabrication of three-dimensional scaffolds for heterogeneous tissue engineering. Biomed Microdevices. 2010 Apr 15; Authors: Han LH, Suri S, Schmidt CE, Chen S The development of biomedical scaffolds mimicking a heterogeneous cellular microenvironment for a specified regulation of cell-fates is very promising for tissue engineering. In this study, three-dimensional scaffolds with heterogeneous microstructure were developed using a DMD-PP apparatus. During the fabrication process, this apparatus can efficiently switch monomers to form microstructures with localized, different material properties; the resolution in the arrangement of material properties is comparable to the characteristic size of functional subunits in living organs, namely, a hundred microns. The effectiveness of this DMD-PP apparatus is demonstrated by a woodpile microstructure with heterogeneous fluorescence and also by a microporous cell-culturing scaffold with selected sites for protein adhesion. Cell-cultivation experiment was performed with the microporous scaffold, in which selective cell adhesion was observed. PMID: 20393801 [PubMed - as supplied by publisher] | | |
| Estimation of relationship between the structure of trihaloacetylazulene derivatives determined by a semiempirical molecular-orbital method (PM5) and their cytotoxicity.
April 16, 2010 at 6:11 AM
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| | Estimation of relationship between the structure of trihaloacetylazulene derivatives determined by a semiempirical molecular-orbital method (PM5) and their cytotoxicity. Anticancer Res. 2010 Mar;30(3):837-41 Authors: Ishihara M, Wakabayashi H, Motohashi N, Sakagami H We have previously reported the cytotoxicity and type of cell death induced by twenty trihaloacetylazulenes in human tumor cell lines. We determined for the first time the most-stable chemical structures from their reported structures, using the semiempirical molecular-orbital method (CONFLEX/PM5), and then delineated the relationship between their cytotoxicity (evaluated by 50% cytotoxic concentration, CC(50)) and a total of twelve parameters. The parameters used are the molecular weight and eleven chemical descriptors: the heat of formation (COSMO, non-COSMO), stability of hydration (=COSMO - nonCOSMO (DeltaH)), dipole moment (D), hydrophobicity (log P), highest occupied molecular orbital energy (E(HOMO)), lowest unoccupied molecular orbital energy (E(LUMO)), absolute hardness [eta=(E(LUMO)-E(HOMO))/2], absolute electron negativity [chi=-(E(LUMO)+E(HOMO))/2], reactivity index (omega=chi(2)/2eta) and surface area (A(2)), and volume of the molecule (A(3)). There w! as good correlation between the CC(50) value and all descriptors except for absolute hardness in HL-60 cells. There was also a good correlation between the CC(50) value and EHOMO, chi, omega, surface area, volume and molecular weight in HSC-2, HSC-3 and HSC-4 cells. The descriptors determined by the present method are useful in evaluating the biological activity of trihaloacetylazulenes. PMID: 20393004 [PubMed - in process] | | |
| iPS cell technology in regenerative medicine.
April 16, 2010 at 6:11 AM
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| | iPS cell technology in regenerative medicine. Ann N Y Acad Sci. 2010 Mar;1192(1):38-44 Authors: Lengner CJ The promise of treating human genetic and degenerative diseases through the application of pluripotent cell-based tissue engineering and regenerative medicine has come significantly closer to realization since the isolation of human embryonic stem (ES) cells. While the study of ES cells has greatly increased our fundamental understanding of pluripotency, technical and ethical limitations have been seemingly insurmountable impediments to the application of these cells in the clinic. The recent discovery that somatic mammalian cells can be epigenetically reprogrammed to a pluripotent state through the exogenous expression of the transcription factors OCT4, SOX2, KLF4, and c-MYC has yielded a new cell type for potential application in regenerative medicine, the induced pluripotent stem (iPS) cell. Here we discuss how advances in iPS cell technology have led to the generation of patient-specific cell lines that can potentially be used to model human diseases and ultim! ately act as therapeutic agents. PMID: 20392216 [PubMed - in process] | | |
| Review of methods used in the reconstruction and rehabilitation of the maxillofacial region.
April 16, 2010 at 6:11 AM
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| | Review of methods used in the reconstruction and rehabilitation of the maxillofacial region. J Ir Dent Assoc. 2010 Feb-Mar;56(1):32-7 Authors: O'Fearraigh P Maxillofacial and dental defects often have detrimental effects on patient health and appearance. A holistic approach of restoring lost dentition along with bone and soft tissue is now the standard treatment of these defects. Recent improvements in reconstructive techniques, especially osseointegration, microvascular free tissue transfer, and improvements in bone engineering, have yielded excellent functional and aesthetic outcomes. This article reviews the literature on these modern reconstructive and rehabilitation techniques. PMID: 20337144 [PubMed - indexed for MEDLINE] | | |
| Quantitative T2 mapping of knee cartilage: differentiation of healthy control cartilage and cartilage repair tissue in the knee with unloading--initial results.
April 16, 2010 at 6:11 AM
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| | Quantitative T2 mapping of knee cartilage: differentiation of healthy control cartilage and cartilage repair tissue in the knee with unloading--initial results. Radiology. 2010 Mar;254(3):818-26 Authors: Mamisch TC, Trattnig S, Quirbach S, Marlovits S, White LM, Welsch GH Purpose: To prospectively determine on T2 cartilage maps the effect of unloading during a clinical magnetic resonance (MR) examination in the postoperative follow-up of patients after matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint. Materials and Methods: Ethical approval for this study was provided by the local ethics commission, and written informed consent was obtained. Thirty patients (mean age, 35.4 years +/- 10.5) with a mean postoperative follow-up period of 29.1 months +/- 24.4 were enrolled. A multiecho spin-echo T2-weighted sequence was performed at the beginning (early unloading) and end (late unloading) of the MR examination, with an interval of 45 minutes. Mean and zonal region of interest T2 measurements were obtained in control cartilage and cartilage repair tissue. Statistical analysis of variance was performed. Results: The change in T2 values of control cartilage (early unloading, 50.2 msec +/- 8.4; late unloadin! g, 51.3 msec +/- 8.5) was less pronounced than the change in T2 values of cartilage repair tissue (early unloading, 51.8 msec +/- 11.7; late unloading, 56.1 msec +/- 14.4) (P = .024). The difference between control cartilage and cartilage repair tissue was not significant for early unloading (P = .314) but was significant for late unloading (P = .036). Zonal T2 measurements revealed a higher dependency on unloading for the superficial cartilage layer. Conclusion: Our results suggest that T2 relaxation can be used to assess early and late unloading values of articular cartilage in a clinical setting and that the time point of the quantitative T2 measurement affects the differentiation between native and abnormal articular cartilage. (c) RSNA, 2010. PMID: 20123898 [PubMed - indexed for MEDLINE] | | |
| Proliferation and differentiation potential of mouse adult hepatic progenitor cells cultured in vitro.
April 16, 2010 at 6:11 AM
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| | Proliferation and differentiation potential of mouse adult hepatic progenitor cells cultured in vitro. Acta Biochim Biophys Sin (Shanghai). 2010 Feb;42(2):122-8 Authors: Song L, Wang H, Gao X, Shen K, Niu W, Qin X This study aimed to isolate the stem cells or progenitors, if exist, from normal adult mouse liver and investigate their potential of proliferation and differentiation. Hepatocytes were isolated by modified two-step liver perfusion method and centrifugation, and then cultured in modified serumcontaining DMEM for observation more than 60 days. Immunofluorescence technique was applied to check the hepatocytes and to examine the formation of colonies with albumin, alpha-fetoprotein (AFP) and cytokeratin 19 (CK19). Results showed that some hepatocytes that were strongly positive for hepatocyte specific markers albumin on Day 1 in culture, could be activated at Days 2-3, followed by rapid proliferation and formation of colonies. The colonies could expand continually for more than 60 days. On Day 5, all the cells in the colony expressed hepatic stem cell (HSC) markers AFP. With the time of culture, some cells in colonies lost ability to divide at Days 13-15, and differe! ntiated into cells which had a large cytoplasm and some two nuclei, similar to the appearance of mature hepatocytes morphologically. These differentiated cells demonstrated strong expression of albumin. Around Day 30, some big cells appeared in colonies and expressed bile duct cell marker CK19. Therefore, this subpopulation of mouse hepatocytes could acquire some characteristics of immature hepatocytes and showed the profile of hepatic progenitor cells with a high proliferating ability and bi-potential of differentiation. They were isolated from normal adult mouse, hence, named adult hepatic progenitor cells (AHPCs). Mouse AHPCs may be used as an HSC model for hepatocytes transplantation and hepatopathy study. PMID: 20119623 [PubMed - indexed for MEDLINE] | | | | 
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