1,113 research outputs found

    Improved isolation and expansion of bone marrow mesenchymal stromal cells using a novel marrow filter device

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    Background aims. Mesenchymal stromal cells (MSCs) have been studied as cell therapy to treat a vast array of diseases. In clinical MSC production, the isolated cells must undergo extensive ex vivo expansion to obtain a sufficient dose of MSCs for the investigational treatment. However, extended tissue culture is fraught with potential hazards, including contamination and most worrisome, malignant transformation. Moreover, changes of gene expression with prolonged culture may alter the therapeutic potential of the cells. Therefore, increasing the recovery of MSCs from the freshly harvested bone marrow allowing for less ex vivo expansion would represent a major advance in MSC therapy. Methods. Human bone marrow cells from 8 healthy donors were processed using a marrow filter device and, in parallel, using buoyant density centrifugation by two independent investigators. The initial nucleated cell recovery as well as the final yield, immunophenotype, and trilineage differentiation potential of passage 2 MSCs were examined. Results. The marrow filter device generated significantly greater initial cell recovery requiring less investigator time and resulted in approximately 2.5-fold more MSCs after passage 2. The immunophenotype and differentiation potential of MSCs isolated using the two methods was equivalent and consistent the defining criteria. The two independent investigators generated comparable results. Conclusions. This novel filter device is a fast, efficient, and reliable system to isolate MSCs and should greatly expedite preclinical and clinical investigations of MSC therapy.Background aims. Mesenchymal stromal cells (MSCs) have been studied as cell therapy to treat a vast array of diseases. In clinical MSC production, the isolated cells must undergo extensive ex vivo expansion to obtain a sufficient dose of MSCs for the investigational treatment. However, extended tissue culture is fraught with potential hazards, including contamination and malignant transformation. Changes of gene expression with prolonged culture may alter the therapeutic potential of the cells. Increasing the recovery of MSCs from the freshly harvested bone marrow allowing for less ex vivo expansion would represent a major advance in MSC therapy. Methods. Human bone marrow cells from eight healthy donors were processed using a marrow filter device and, in parallel, using buoyant density centrifugation by two independent investigators. The initial nucleated cell recovery and the final yield, immunophenotype and trilineage differentiation potential of second-passage MSCs were examined. Results. The marrow filter device generated significantly greater initial cell recovery requiring less investigator time and resulted in approximately 2.5-fold more MSCs after the second passage. The immunophenotype and differentiation potential of MSCs isolated using the two methods were equivalent and consistent with the defining criteria. The two independent investigators generated comparable results. Conclusions. This novel filter device is a fast, efficient and reliable system to isolate MSCs and should greatly expedite pre-clinical and clinical investigations of MSC therapy. © 2013, International Society for Cellular Therapy

    From self assembled monolayers to clickable gold nanoparticles

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    The aim of the present PhD thesis was the investigation of the behavior of gold nanoparticle stabilizing oligo thioether ligands on gold surfaces and further on to develop a protocol for the directed assembly of mono functionalized gold nanoparticle into defined oligomer structures. Outline The present cumulative PhD thesis consists of the following parts: In the Introduction the research field of gold nanoparticles is presented with to point out their unique electronic and physical properties. The second focus will be on the controlled interlinking and functionalization of gold nanoparticles using click chemistry and their potential applications, which will be submitted as a review article. Within Concept and Strategy the goals of the research project are introduced and the concepts and outputs of the resulting publications are presented. The Publications are accumulated with their respective Supporting Information, in the order in which they were prepared: “Loops versus Stems: Benzylic Sulfide Oligomers Forming Carpet Type Monolayers“ F. Sander, T. Peterle, N. Ballav, F. Wrochem, M. Zharnikov, M. Mayor J. Phys. Chem. C, 2010, 114, 4118 – 4125. “Add a Third Hook: S-Acetyl Protected Oligophenylene Pyridine Dithiols as Advanced Precursors for Self-Assembled Monolayers“ F. Sander, J. P. Hermes, M. Mayor, H. Hamoudi, M. Zharnikov PCCP, 2013, 15, 2836 – 2846. “Dumbbells, Trikes and Quads - Click Gold Nanopartricles together“ F. Sander, U. Fluch, J. P. Hermes and M. Mayor Small 2014, 10, 349 – 359. “Click Chemistry with Gold Nanoparticles – A Tool for Functionalization, Interlinking and Labeling” Fabian Sander and Marcel Mayor, manuscript prepared for submission. Finally, within Conclusion and Outlook the main results are briefly summarized and further potential research is proposed

    Keeping It Real in the Hills: Representing Appalachia in Americana Music

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    KEEPING IT REAL IN THE HILLS: REPRESENTING APPALACHIA IN AMERICANA was led by leading author, journalist and media personality Craig Havighurst and panelists radio producer Kris Truelsen, artist Kathy Mattea, artist Amythyst Kiah, and music educator Ted Olson. The topic of discussion was the state of old-time and Appalachian folk music and its sounds today, and the making of Kathy Mattea’s album Calling Me Home

    Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning

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    Successful hematopoietic stem cell (HSC) transplantation requires donor HSC engraftment within specialized bone marrow microenvironments known as HSC niches. We have previously reported a profound remodeling of the endosteal osteoblastic HSC niche after total body irradiation (TBI), defined as relocalization of surviving megakaryocytes to the niche site and marked expansion of endosteal osteoblasts. We now demonstrate that host megakaryocytes function critically in expansion of the endosteal niche after preparative radioablation and in the engraftment of donor HSC. We show that TBI-induced migration of megakaryocytes to the endosteal niche depends on thrombopoietin signaling through the c-MPL receptor on megakaryocytes, as well as CD41 integrin-mediated adhesion. Moreover, niche osteoblast proliferation post-TBI required megakaryocyte-secreted platelet-derived growth factor-BB. Furthermore, blockade of c-MPL-dependent megakaryocyte migration and function after TBI resulted in a significant decrease in donor HSC engraftment in primary and competitive secondary transplantation assays. Finally, we administered thrombopoietin to mice beginning 5 days before marrow radioablation and ending 24 hours before transplant to enhance megakaryocyte function post-TBI, and found that this strategy significantly enhanced donor HSC engraftment, providing a rationale for improving hematopoietic recovery and perhaps overall outcome after clinical HSC transplantation.Successful hematopoietic stem cell (HSC) transplantation requires donor HSC engraftment within specialized bone marrow microenvironments known as HSC niches. We have previously reported a profound remodeling of the endosteal osteoblastic HSC niche after total body irradiation (TBI), defined as relocalization of surviving megakaryocytes to the niche site and marked expansion of endosteal osteoblasts. We now demonstrate that host megakaryocytes function critically in expansion of the endosteal niche after preparative radioablation and in the engraftment of donor HSC. We show that TBI-induced migration of megakaryocytes to the endosteal niche depends on thrombopoietin signaling through the c-MPL receptor on megakaryocytes, as well as CD41 integrin-mediated adhesion. Moreover, niche osteoblast proliferation post-TBI required megakaryocyte-secreted platelet-derived growth factor-BB. Furthermore, blockade of c-MPL-dependent megakaryocyte migration and function after TBI resulted in a significant decrease in donor HSC engraftment in primary and competitive secondary transplantation assays. Finally, we administered thrombopoietin to mice beginning 5 days before marrow radioablation and ending 24 hours before transplant to enhance megakaryocyte function post-TBI, and found that this strategy significantly enhanced donor HSC engraftment, providing a rationale for improving hematopoietic recovery and perhaps overall outcome after clinical HSC transplantation

    Genomic and functional comparison of mesenchymal stromal cells prepared using two isolation methods

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    Background aims: Mesenchymal stromal cells (MSCs) have been applied to patients in cell therapy for various diseases. Recently, we introduced a novel MSC separation filter device which could yield approximately 2.5-fold more MSCs from bone marrow in a closed system compared with the conventional open density gradient centrifugation method. MSCs isolated with these two methods were phenotypically similar and met the criteria defining human MSC proposed by the International Society for Cellular Therapy. However, these criteria do not reflect the functional capacity of MSCs. It has been shown that the donor, source, isolation method, culture condition and cryopreservation of MSCs have potential to alter their therapeutic efficacy. To determine the equivalency of MSCs isolated by these two methods, we compared their genomic profiles as an index of their biologic potential and evaluated their growth promoting potential as an index of function. Methods: The gene expression profiles of human MSCs isolated from 5 healthy donors with two distinct methods were obtained from microarray analyses. The functional activity of freshly expanded/cryopreserved MSCs from these two isolation methods was evaluated using an invitro chondrocyte proliferation assay. Results: Freshly expanded MSCs isolated by these two methods were found to exhibit similar gene expression profiles and equivalent therapeutic effects, while freshly thawed, cryopreserved MSCs lacked all measureable therapeutic activity. Conclusions: The MSC separation device generates genomically and functionally equivalent MSCs compared with the conventionally isolated MSCs, although freshly thawed, cryopreserved MSCs, isolated by either method, are devoid of activity in our bioassay

    A novel method to test non-exclusive hypotheses applied to Arctic ice projections from dependent models

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    © 2019, The Author(s).A major conundrum in climate science is how to account for dependence between climate models. This complicates interpretation of probabilistic projections derived from such models. Here we show that this problem can be addressed using a novel method to test multiple non-exclusive hypotheses, and to make predictions under such hypotheses. We apply the method to probabilistically estimate the level of global warming needed for a September ice-free Arctic, using an ensemble of historical and representative concentration pathway 8.5 emissions scenario climate model runs. We show that not accounting for model dependence can lead to biased projections. Incorporating more constraints on models may minimize the impact of neglecting model non-exclusivity. Most likely, September Arctic sea ice will effectively disappear at between approximately 2 and 2.5 K of global warming. Yet, limiting the warming to 1.5 K under the Paris agreement may not be sufficient to prevent the ice-free Arcti

    Pulmonary trematodosis (Pharyngostomoides sp.) in a juvenile raccoon (Procyon lotor)

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    © 2011 The Author(s)Accession Number: 21908291. Language: English. Language Code: eng. Date Created: 20110912. Date Completed: 20120113. Update Code: 20120113. Publication Type: Case Reports; Journal Article. Journal ID: 9011490. Publication Model: Print. Cited Medium: Internet. NLM ISO Abbr: J. Vet. Diagn. Invest. Linking ISSN: 10406387. Subset: IM. Date of Electronic Publication: 20110501; ID: 21908291Source type: Electronic(1

    Viren (Edwin) interview

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    Holdrege, Nebraska, United StatesEdwin Viren's parents emigrated from Sweden in the early 1900s and settled in Nebraska. Mr. Viren speaks about his parents and four brothers, his childhood in Nebraska, and other Swedish relatives that settled in the area. Near the end of the interview, Mr. Viren's wife, Margaret, speaks about her mother-in-law and adjusting to Swedish family customs. Subject timestamps: (0:19) Early family history, (0:53) Father's immigration in 1903, (2:15) Obtaining US citizenship papers, (2:44) Father learning English, (3:15) Mother's immigration in 1904, (3:45) Names and birth dates of brothers, (5:01) Grandfather's work as farmer, (5:45) Reasons for settling in Nebraska, (6:39) Relatives settled in US before parents, Anders Olson and Aluminum Company of America, (10:36) Father's career as a builder, landlord, (14:50) Father's character, sense of independence, (16:50) Tale of gambling uncle, (17:58) Anders Olson's immigration, (18:40) Father's work in Sweden making charcoal, (20:45) Career, training as a carpenter, (21:35) Living in other Nebraska towns, raising cattle, (24:18) Speaking Swedish as a child, learning English in school, (25:34) Uncle, Ernie Sundberg, (28:44) Speaking English and Swedish with cousin, (29:17) Name of wife and son, (30:10) Illnesses and injuries as children, (33:17) Attending Lutheran church in Nebraska, confirmation, (36:07) Parents' return visits to Sweden, (38:41) Halloween pranks in Loomis, (39:53) Communicating with Edwin's mother, adjusting to Swedish customs, (42:03) Swedish foods, cooking and washing, (43:28) Making rugs on a loom, (45:38) Christmas foods- lutefisk, (46:14) Fuel for mother's cook stove This accession is part of the Scandinavian Archives Project. The Sundberg Nordic Oral History Collection was a project emphasizing Scandinavian emigration and settlement in the US. The interviews were taped by Edward and Gerda Sundberg during a sabbatical from Cabrillo College in 1976. Sundberg S-20a, S-20bTo request a high resolution or uncompressed reproduction, or to obtain permission to use any portion of this item, contact the University of Washington Libraries, Special Collections. Email: [email protected]. Please reference the Digital ID Number

    MANCUR OLSON E A LÓGICA DA AÇÃO COLETIVA APLICADA AO MST

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    This paper aims to discuss Mancur Olson ideas about the collective action applied to Landless Workers' Movement(MST) settlements of agrarian reform. The author's idea is that individuals only participate in collective action when these may bring them individual profits. In the present article we try to demonstrate that there's more than personal interest on collective actions strategy. These actions also denote the criation of new values (friendship, solidarity) that don't behave only as purely pragmatic interests.Este artigo busca discutir as ideias de MancurOlson sobre a ação coletiva aplicada a assentamentos de reforma agrária do Movimento dos Trabalhadores Rurais Sem Terra (MST). A ideia de Olson (1999) é que os indivíduos só participam de ações coletivas quando estas possam lhes trazer lucros individuais. No presente artigo tentamos demonstrar que existem mais do que interesse individual nas estratégias de ações coletivas. Nestas ações, denotam-se também a criação de novos valores (amizade, solidariedade) que não se comportam apenas como interesses puramente pragmáticos
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