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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.
April 16, 2010 at 8:12 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] | | |
| Fabrication of three-dimensional scaffolds for heterogeneous tissue engineering.
April 16, 2010 at 8:12 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] | | |
| Challenges in using stem cells for cardiac repair.
April 16, 2010 at 8:12 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] | | |
| Estimation of relationship between the structure of trihaloacetylazulene derivatives determined by a semiempirical molecular-orbital method (PM5) and their cytotoxicity.
April 16, 2010 at 8:12 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 8:12 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 8:12 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 8:12 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 8:12 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] | | |
| Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.
April 16, 2010 at 8:12 AM
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| | Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation. Exp Hematol. 2010 Apr;38(4):270-81 Authors: Davis TA, Landauer MR, Mog SR, Barshishat-Kupper M, Zins SR, Amare MF, Day RM OBJECTIVE: Angiotensin II (Ang II), a potent vasoconstrictor, affects the growth and development of hematopoietic cells. Mixed findings have been reported for the effects of angiotensin-converting enzyme (ACE) inhibitors on radiation-induced injury to the hematopoietic system. We investigated the consequences of different regimens of the ACE inhibitor captopril on radiation-induced hematopoietic injury. MATERIALS AND METHODS: C57BL/6 mice were either sham-irradiated or exposed to (60)Co total body irradiation (0.6 Gy/min). Captopril was provided in the water for different time periods relative to irradiation. RESULTS: In untreated mice, the survival rate from 7.5 Gy was 50% at 30 days postirradiation. Captopril treatment for 7 days prior to irradiation resulted in radiosensitization with 100% lethality and a rapid decline in mature blood cells. In contrast, captopril treatment beginning 1 hour postirradiation and continuing for 30 days resulted in 100% survival, w! ith improved recovery of mature blood cells and multilineage hematopoietic progenitors. In nonirradiated control mice, captopril biphasically modulated Lin(-) marrow progenitor cell cycling. After 2 days, captopril suppressed G(0)-G(1) transition and a greater number of cells entered a quiescent state. However, after 7 days of captopril treatment Lin(-) progenitor cell cycling increased compared to untreated control mice. CONCLUSION: These findings suggest that ACE inhibition affects hematopoietic recovery following radiation by modulating the hematopoietic progenitor cell cycle. The timing of captopril treatment relative to radiation exposure differentially affects the viability and repopulation capacity of spared hematopoietic stem cells and, therefore, can result in either radiation protection or radiation sensitization. PMID: 20116413 [PubMed - indexed for MEDLINE] | | |
| Characterizing functional stem cell-cardiomyocyte interactions.
April 16, 2010 at 8:12 AM
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| | Characterizing functional stem cell-cardiomyocyte interactions. Regen Med. 2010 Jan;5(1):87-105 Authors: Bursac N, Kirkton RD, McSpadden LC, Liau B Despite the progress in traditional pharmacological and organ transplantation therapies, heart failure still afflicts 5.3 million Americans. Since June 2000, stem cell-based approaches for the prevention and treatment of heart failure have been pursued in clinics with great excitement; however, the exact mechanisms of how transplanted cells improve heart function remain elusive. One of the main difficulties in answering these questions is the limited ability to directly access and study interactions between implanted cells and host cardiomyocytes in situ. With the growing number of candidate cell types for potential clinical use, it is becoming increasingly more important to establish standardized, well-controlled in vitro and in situ assays to compare the efficacy and safety of different stem cells in cardiac repair. This article describes recent innovative methodologies to characterize direct functional interactions between stem cells and cardiomyocytes, aimed t! o facilitate the rational design of future cell-based therapies for heart disease. PMID: 20017697 [PubMed - indexed for MEDLINE] | | |
| In vivo neural stem cell imaging: current modalities and future directions.
April 16, 2010 at 8:12 AM
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| | In vivo neural stem cell imaging: current modalities and future directions. Regen Med. 2010 Jan;5(1):73-86 Authors: Gera A, Steinberg GK, Guzman R Neural stem cells have been proposed as a promising therapy for treating a wide variety of neuropathologies. While several studies have demonstrated the therapeutic benefits of neural stem cells, the exact mechanism remains elusive. In order to facilitate research efforts to understand these mechanisms, and before neural stem cell-based therapies can be utilized in a clinical context, we must develop means of monitoring these cells in vivo. However, because of tissue depth and the blood-brain barrier, in vivo imaging of neural stem cells in the brain has unique challenges that do not apply to stem cells for other purposes. In this paper, we review contemporary methods for in vivo neural stem cell imaging, including MRI, PET and optical imaging techniques. PMID: 20017696 [PubMed - indexed for MEDLINE] | | |
| Progenitor cell therapy for traumatic brain injury: effect of serum osmolarity on cell viability and cytokine production.
April 16, 2010 at 8:12 AM
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| | Progenitor cell therapy for traumatic brain injury: effect of serum osmolarity on cell viability and cytokine production. Regen Med. 2010 Jan;5(1):65-71 Authors: Walker PA, Jimenez F, Cox CS INTRODUCTION: The potential translation of mesenchymal stem cell (MSC) therapy into a multimodal protocol for traumatic brain injury requires evaluation of viability and cytokine production in a hyperosmolar environment. Optimization of MSC therapy requires delivery to the target area without significant loss of cellular function or viability. No model evaluating the potential efficacy of MSC therapy at varying osmolarities currently exists. METHODS: Rat MSCs were characterized with flow cytometric immunophenotyping. MSCs (passage 3) were placed in culture with multipotent adult progenitor cell media at varying osmolarities (250, 270, 290, 310, 330, 350 and 370 mOsm) potentially found with hypertonic saline infusion. After culture for 24 h, cellular viability was measured using flow cytometry (n = 6). Next, brain tissue supernatant was harvested from both normal rat brains and injured brains 6 h after cortical injury. Subsequently, MSCs were placed in culture with! multipotent adult progenitor cell media +/- 20% normal brain or injured brain supernatant (at the aforementioned osmolarities) and allowed to remain in culture for 24 h (n = 11). At this point, media supernatant cytokine levels were measured using a multiplex cytokine assay system. RESULTS: MSCs showed no clinically significant difference in viability at 24 h. MSCs cultured with 20% injured brain supernatant showed an decrease in proinflammatory cytokine production (IL-1alpha and IL-1beta) with increasing osmolarity. No difference in anti-inflammatory cytokine production (IL-4 and IL-10) was observed. CONCLUSION: Progenitor cell therapy for traumatic brain injury may require survival and activity in a hyperosmolar environment. Culture of MSCs in such conditions shows no clinically significant effect on cell viability. In addition, MSC efficacy could potentially be enhanced via a decrease in proinflammatory cytokine production. Overall, a multimodal traumatic brain injury t! reatment protocol based upon MSC infusion and hypertonic salin! e therap y would not negatively affect progenitor cell efficacy and could be considered for multicenter clinical trials. PMID: 20017695 [PubMed - indexed for MEDLINE] | | |
| Development of a calcium-chelating hydrogel for treatment of superficial burns and scalds.
April 16, 2010 at 8:12 AM
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| | Development of a calcium-chelating hydrogel for treatment of superficial burns and scalds. Regen Med. 2010 Jan;5(1):55-64 Authors: Bullock AJ, Pickavance P, Haddow DB, Rimmer S, MacNeil S AIMS: Superficial burns and scalds are usually managed conservatively with traditional dressings. Failure to heal within 3 weeks leads to their management by skin grafting. Our aim was to develop a biomaterial to actively promote keratinocyte migration in superficial burns by modulating local cation concentrations to accelerate keratinocyte migration and deter wounds from contracting, thus potentially reducing the number of such wounds requiring grafting. MATERIALS & METHODS: We investigated polymeric hydrogels for their Ca(2+) chelating properties and enhancement of keratinocyte migration in human tissue-engineered skin models. RESULTS: Dimethylaminoethyl methacrylate:methacrylic acid hydrogel coupled with elevated [Mg(2+)] reduced media [Ca(2+)], potentiating keratinocyte migration in tissue-engineered skin models, it also significantly reduced wound model contraction. CONCLUSION: Dimethylaminoethyl methacrylate:methacrylic acid hydrogels could promote wound! healing and reduce wound contraction, a significant complication in burn wound healing. PMID: 20017694 [PubMed - indexed for MEDLINE] | | |
| Human umbilical cord blood mononuclear cells decrease fibrosis and increase cardiac function in cardiomyopathy.
April 16, 2010 at 8:12 AM
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| | Human umbilical cord blood mononuclear cells decrease fibrosis and increase cardiac function in cardiomyopathy. Regen Med. 2010 Jan;5(1):45-54 Authors: Henning RJ, Aufman J, Shariff M, Sawmiller D, DeLostia V, Sanberg P, Morgan M AIMS: We investigated whether human umbilical cord blood mononuclear cells (HUCBC) can limit progressive cardiomyopathy in TO2 hamsters. MATERIALS & METHODS: A total of 22 TO2 1-month-old hamsters were treated with intramyocardial HUCBC, 4 x 10(6) in Isolyte, and 23 TO2 1-month-old hamsters were treated with intramyocardial Isolyte. A total of 16 1-month-old F1B hamsters served as controls and received intramyocardial Isolyte. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were then stained with hematoxylin and eosin, Masson's Trichrome and human leukocyte antibody. RESULTS: In F1B hamsters, left ventricular fractional shortening (FS) and ejection fractions (EF) did not significantly decrease over 6 months. By contrast, in Isolyte-treated TO2 hamsters, FS decreased from 56.2 +/- 1.0% to 19.7 +/- 3.2% and EF decreased from 89.5 +/- 1.4% to 44.9 +/- 5.9% at 6 months (both p < 0.0001). The FS and! EF in HUCBC-treated TO2 hamsters also progressively decreased over 6 months but the changes were more gradual, especially during the first month after HUCBC treatment when FS was 52.0 +/- 1.5% and EF was 89.5 +/- 1.4%, which was not significantly different from the FS and EF in the F1B hamsters. Moreover, in the HUCBC-treated hamsters, the FS and EF were 20-30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p < 0.01). In Isolyte-treated TO2 hamsters at 6-7 months, fibrosis involved 30.0 +/- 5.0% of left ventricle and 35.0 +/- 5.0% of septum. By contrast, in HUCBC-treated hamsters, fibrosis involved only 6.5 +/- 2.3% of the left ventricle and 6.3 +/- 1.8% of septum (p < 0.05). The average number of blood vessels per myocardial microscopic field in HUCBC-treated hearts was 53.5 +/- 0.8 versus 46.2 +/- 3.0 in Isolyte-treated TO2 hearts (p < 0.05). CONCLUSION: HUCBC, when given as a single intramyocardial injection, can limit fibrosis and increase h! eart function over the short term in TO2 hamsters with cardiom! yopathy. PMID: 20017693 [PubMed - indexed for MEDLINE] | | |
| Tracking the rise of stem cell tourism.
April 16, 2010 at 8:12 AM
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| | Tracking the rise of stem cell tourism. Regen Med. 2010 Jan;5(1):27-33 Authors: Ryan KA, Sanders AN, Wang DD, Levine AD AIMS: Driven by hype surrounding stem cell research, a number of clinics around the world currently offer 'stem cell therapies' to patients. These unproven interventions have attracted policy interest owing to the risks they may pose to patients and to the progress of legitimate translational stem cell research, yet remarkably little data exists about the patients who undergo these unproven therapies or their experiences. We sought to characterize this patient population. MATERIALS & METHODS: We developed a comprehensive data set of blogs written by patients (or their caretakers) about their experiences with unproven stem cell therapies. RESULTS & CONCLUSIONS: Analyzing these data suggests that unproven stem cell therapies are increasing rapidly in popularity and are attracting a wide range of patients--both young and old and with a diverse collection of medical conditions. These results should help clinicians advise individual patients and help policymake! rs devise strategies to mitigate the risks these treatments pose. PMID: 20017692 [PubMed - indexed for MEDLINE] | | |
| Stem cell charter.
April 16, 2010 at 8:12 AM
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| | Stem cell charter. Regen Med. 2010 Jan;5(1):5-6 Authors: Knoppers BM, Isasi R, Willemse L PMID: 20017687 [PubMed - indexed for MEDLINE] | | | | 
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