59 research outputs found

    Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies

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    Appendix B: A report on the visit to the region stricken by the Wenchuan Earthquake

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    Earthquake ground shaking is one of the environmental actions to be considered in structural design. In regions of high seismicity, the design of structural elements is usually governed by load combinations which include seismic loading. The effects of an earthquake on non-structural elements such as damage to facades, glass, plasters, veneers, gas and water pipes, etc. can also be a significant issue even in the regions with low-to-moderate seismic activity. The Wenchuan Earthquake with the moment magnitude of 7.9 (reported by USGS) occurred in Sichuan Province in China on May 12, 2008 at local time 14:28. As of July 2 2008, 69,195 people have been killed, 373,606 injured, 18,389 missing, 5 million homeless, and 79,852 rescued (Ref. 3). To investigate damage to infrastructure caused by this earthquake, a group of 8 researchers (2 from The University of Melbourne, 1 from Swinburne University of Technology and 5 from The University of Hong Kong) was sent to Sichuan, China in late June-early July 2008 (about 50 days after the event) for visiting the city of Chengdu, Dujiangyang, YingXiu and Mianyang cities which have suffered different degrees of damage. This report is mainly on the observations of the damaged area. The aim herein is to classify damage based on building types, modes of failure, distance from the epicentre and relevant ground motion parameters

    The Effect Of 8 Day Storage At 4˚C On Total Nucleated Cell Count, Cell Viability, And Granulocyte-Macrophage Colony Forming Unit Of Mobilized Peripheral Blood

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    Background: Hematopoietic stem cell (HSC) transplantation has brought the possibility of the use of high dose chemotherapy in the treatment of malignant hematopoietic diseases. Short-term HSC preservation at 4˚C is the most common method for autologous peripheral blood stem cell transplantation (PBSCT). Materials and Methods: Thirty-seven mobilized PBSC samples from thirteen hematological patients (4 AML, 4 MM and 5 Lymphoma cases) who were selected for autologous PBSCT and 24 normal candidates for allogenic PBSCT were preserved in five separate sterile 2 ml tubes in 4˚C. Each sample was evaluated for total nucleated cell (TNC) count, dye exclusion cell viability and Granulocyte-Macrophage colony forming unit (GM-CFU; in semisolid medium after 16 days) in days 0, 2, 4, 6 and 8. The results were converted to percentages of day 0 measures. The data were analyzed by SPSS 10.0 using Paired Samples T test, Independent Samples T test and Regression. Results: The mean percentages (and standard deviations) of TNC count, cell viability and GM-CFU for days 0, 2, 4, 6 and 8 are shown below: No significant correlation was found between age, sex, weight and the kind of donor with TNC, viability and GM-CFU. Conclusion: In this study, we have found that during storage of mobilized PBSC in 4˚C, TNC count and cell viability still remains higher than 70% after eight days, while GM-CFU decreases more rapidly and falls to less than 50% after day 4.Therefore, TNC count and cell viability do not decrease as fast as GM-CFU

    Assessment of in vitro aging of mesenchymal stem cell

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    Mesenchyml stem cell (MSC) are receiving much attention in treatment of various diseases. The low frequency of MSCs in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of long term culture on the senescence of these cells."nBM cells were taken from 11 transplant donors with mean age of 25 years. In different passages, MSC were examined for different aging indicators including: telomere length assay, differentiation ability, immunophenotyping of CD13, CD44 and CD34 antigens, determination of cumulative population dou¬blings (CPDs), and study of morphological characteristics of MSC cultures."nThe mean long term culture was 118 day and the mean passage number was 9. The average number of PD decreased from 7.7 to 1.2 in the 10th passage. The mean telomere length decreased from 9.19 Kbp to 8.7 kbp in the 9th passage. Differentiation potential dropped from the 6th passage on. The culture's morphological abnormalities were typical of the Hayflick model of cellular aging. We believe that MSC enter senescence almost undetectably from the moment of in vitro culturing. Si¬multaneously these cells are losing their stem cell characteristics. Therefore, it is much better to con¬sider them for cell and gene therapy early on

    Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.

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    BACKGROUND: More than half of patients with multiple sclerosis have progressive disease characterised by accumulating disability. The absence of treatments for progressive multiple sclerosis represents a major unmet clinical need. On the basis of evidence that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of multiple sclerosis, we aimed to assess the safety and efficacy of these cells as a potential neuroprotective treatment for secondary progressive multiple sclerosis. METHODS: Patients with secondary progressive multiple sclerosis involving the visual pathways (expanded disability status score 5·5-6·5) were recruited from the East Anglia and north London regions of the UK. Participants received intravenous infusion of autologous bone-marrow-derived mesenchymal stem cells in this open-label study. Our primary objective was to assess feasibility and safety; we compared adverse events from up to 20 months before treatment until up to 10 months after the infusion. As a secondary objective, we chose efficacy outcomes to assess the anterior visual pathway as a model of wider disease. Masked endpoint analyses was used for electrophysiological and selected imaging outcomes. We used piecewise linear mixed models to assess the change in gradients over time at the point of intervention. This trial is registered with ClinicalTrials.gov, number NCT00395200. FINDINGS: We isolated, expanded, characterised, and administered mesenchymal stem cells in ten patients. The mean dose was 1·6×10(6) cells per kg bodyweight (range 1·1-2·0). One patient developed a transient rash shortly after treatment; two patients had self-limiting bacterial infections 3-4 weeks after treatment. We did not identify any serious adverse events. We noted improvement after treatment in visual acuity (difference in monthly rates of change -0·02 logMAR units, 95% CI -0·03 to -0·01; p=0·003) and visual evoked response latency (-1·33 ms, -2·44 to -0·21; p=0·020), with an increase in optic nerve area (difference in monthly rates of change 0·13 mm(2), 0·04 to 0·22; p=0·006). We did not identify any significant effects on colour vision, visual fields, macular volume, retinal nerve fibre layer thickness, or optic nerve magnetisation transfer ratio. INTERPRETATION: Autologous mesenchymal stem cells were safely given to patients with secondary progressive multiple sclerosis in our study. The evidence of structural, functional, and physiological improvement after treatment in some visual endpoints is suggestive of neuroprotection. FUNDING: Medical Research Council, Multiple Sclerosis Society of Great Britain and Northern Ireland, Evelyn Trust, NHS National Institute for Health Research, Cambridge and UCLH Biomedical Research Centres, Wellcome Trust, Raymond and Beverly Sackler Foundation, and Sir David and Isobel Walker Trust
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