Sobre limites: embriões e a ANT
Paper presented in the panel “A composição do social: coletando humanos e não-humanos”, 26th Brazilian Anthropology Meeting, June 1-4, 2010, Porto Seguro, Bahia, Braszil.
A comunicação baseia-se no resultado de pesquisa realizada entre 2004 e 2005 sobre a tramitação do Projeto de Lei da... more A comunicação baseia-se no resultado de pesquisa realizada entre 2004 e 2005 sobre a tramitação do Projeto de Lei da Biossegurança no Congresso Nacional brasileiro. Tal legislação visou regular a pesquisa e comercialização de organismos geneticamente modificados (OGMs) e a pesquisa com células-tronco embrionárias humanas (CTEHs) no país. Originalmente realizada dentro do escopo da teoria do ator-rede (ANT), em especial conforme delineada por Latour em seu Políticas da Natureza, a análise do material empírico posteriormente suscitou importantes questões a serem colocadas para a própria teoria. Em especial, o lugar (cosmológico e prático) central do livre-mercado e da ideologia do progresso na composição da rede que deu forma final às regras para OGMs, e, no caso das células- tronco, uma hierarquização interna à categoria do "humano" guiando a liberação parcial de embriões excedentes para a pesquisa terapêutica com CTEHs, parecem sugerir a necessidade de um diálogo maior entre a ANT e outras vertentes teóricas, por exemplo, economia política e estudos sobre a noção de "pessoa". A comunicação traz uma tentativa de tal diálogo no último caso, onde um maior aprofundamento histórico e comparativo em torno das noções de "indivíduo", "vida", e "humano" mostrou-se profícuo para refinar a compreensão teórica sobre a problemática dos embriões.
Regenerative Nanomedicine: Ethical, Legal, and Social Issues
Co-authored with Dr. Jeannann S. Boyce, published in Methods in Molecular Biology, 2012
Advances in regenerative nanomedicine raise a host of ethical, legal, and social questions that healthcare providers... more Advances in regenerative nanomedicine raise a host of ethical, legal, and social questions that healthcare providers and scientists will need to consider. These questions and concerns include definitions, appropriate applications, dual use, potential risks, regulations, and access. In this chapter, we provide an overview of the questions and concerns and recommend proactive consideration and solutions.
Transcriptomics Comparison between Porcine Adipose and Bone Marrow Mesenchymal Stem Cells during In Vitro Osteogenic and Adipogenic Differentiation
Co-authored with Elisa Monaco, Sandra Rodriguez-Zas, Walter L Hurley, and Matthew B Wheeler
Bone-marrow mesenchymal stem cells (BMSC) are considered the gold standard for use in tissue regeneration among... more Bone-marrow mesenchymal stem cells (BMSC) are considered the gold standard for use in tissue regeneration among mesenchymal stem cells (MSC). The abundance and ease of harvest make the adipose-derived stem cells (ASC) an attractive alternative to BMSC. The aim of the present study was to compare the transcriptome of ASC and BMSC, respectively isolated from subcutaneous adipose tissue and femur of 3 adult pigs, during in vitro osteogenic and adipogenic differentiation for up to four weeks. At 0, 2, 7, and 21 days of differentiation RNA was extracted for microarray analysis. A False Discovery Rate ≤0.05 for overall interactions effect and P<0.001 between comparisons were used to determine differentially expressed genes (DEG). Ingenuity Pathway Analysis and DAVID performed the functional analysis of the DEG. Functional analysis of highest expressed genes in MSC and genes more expressed in MSC vs. fully differentiated tissues indicated low immunity and high angiogenic capacity. Only 64 genes were differentially expressed between ASC and BMSC before differentiation. The functional analysis uncovered a potential larger angiogenic, osteogenic, migration, and neurogenic capacity in BMSC and myogenic capacity in ASC. Less than 200 DEG were uncovered between ASC and BMSC during differentiation. Functional analysis also revealed an overall greater lipid metabolism in ASC, while BMSC had a greater cell growth and proliferation. The time course transcriptomic comparison between differentiation types uncovered <500 DEG necessary to determine cell fate. The functional analysis indicated that osteogenesis had a larger cell proliferation and cytoskeleton organization with a crucial role of G-proteins. Adipogenesis was driven by PPAR signaling and had greater angiogenesis, lipid metabolism, migration, and tumorigenesis capacity. Overall the data indicated that the transcriptome of the two MSC is relatively similar across the conditions studied. In addition, functional analysis data might indicate differences in therapeutic application.
Cellular and Molecular Determinants of Stroke-Induced Changes in Subventricular Zone Cell Migration
Young CC, Brooks KJ, Buchan AM, Szele FG.
Department of Physiology, Anatomy and Genetics, University of... more
Young CC, Brooks KJ, Buchan AM, Szele FG.
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
A remarkable aspect of adult neurogenesis is that the tight regulation of subventricular zone (SVZ) neuroblast migration is altered after ischemic stroke and newborn neurons emigrate towards the injury. This phenomenon is an essential component of endogenous repair and also serves to illuminate normal mechanisms and rules that govern SVZ migration. Stroke causes inflammation that leads to cytokine and chemokine release, and SVZ neuroblasts that express their receptors are recruited. Metalloproteinases create pathways and new blood vessels provide a scaffold to facilitate neuroblast migration between the SVZ and the infarct. Most experiments have studied the peri-lesion parenchyma and relatively little is known about SVZ remodeling after stroke. Migration in the SVZ is tightly regulated by cellular interactions and molecular signaling; how are these altered after stroke to allow emigration? Do ependymal cells contribute to this process, given their reported neurogenic potential? How does stroke affect ependymal cell regulation of cerebrospinal fluid flow? Given the heterogeneity of SVZ progenitors, do all types of neuroblasts migrate out, or is this confined to specific subtypes of cells? We discuss these and other questions in our review and propose experiments to address them.
Ependymal Ciliary Dysfunction and Reactive Astrocytosis in a Reorganized Subventricular Zone after Stroke
Published in "Cerebral Cortex"
Young CC, van der Harg JM, Lewis NJ, Brooks KJ, Buchan AM, Szele FG.
Department of Physiology, Anatomy and... more
Young CC, van der Harg JM, Lewis NJ, Brooks KJ, Buchan AM, Szele FG.
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX13QX, UK
Subventricular zone (SVZ) astrocytes and ependymal cells are both derived from radial glia and may have similar gliotic reactions after stroke. Diminishing SVZ neurogenesis worsens outcomes in mice, yet the effects of stroke on SVZ astrocytes and ependymal cells are poorly understood. We used mouse experimental stroke to determine if SVZ astrocytes and ependymal cells assume similar phenotypes and if stroke impacts their functions. Using lateral ventricular wall whole mount preparations, we show that stroke caused SVZ reactive astrocytosis, disrupting the neuroblast migratory scaffold. Also, SVZ vascular density and neural proliferation increased but apoptosis did not. In contrast to other reports, ependymal denudation and cell division was never observed. Remarkably, however, ependymal cells assumed features of reactive astrocytes post stroke, robustly expressing de novo glial fibrillary acidic protein, enlargening and extending long processes. Unexpectedly, stroke disrupted motile cilia planar cell polarity in ependymal cells. This suggested ciliary function was affected and indeed ventricular surface flow was slower and more turbulent post stroke. Together, these results demonstrate that in response to stroke there is significant SVZ reorganization with implications for both pathophysiology and therapeutic strategies.
Cellular therapies for treating pain associated with spinal cord injury. Leung, L.
Journal of Translational Medicine 2012, 10:37
Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical... more Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing.
Embriões e células-tronco embrionárias têm direito à vida?
Ethic@, 4, 3, 2005: 301-308.
Na polêmica em torno da permissão ou proibição da pesquisa com células-tronco embrionárias freqüentemente são... more Na polêmica em torno da permissão ou proibição da pesquisa com células-tronco embrionárias freqüentemente são empregados argumentos que apelam a considerações sobre direitos. Porém, faz sentido dizer que embriões têm direitos? Há argumentos fortemente plausíveis em favor da tese de que embriões de laboratório não são seres candidatos a terem direitos. Da alegação, por exemplo, de que se tratam de pessoas em potencial não se segue que pré-embriões possuam quaisquer direitos, já que ninguém tem direitos equivalentes aos de outrem pelo fato de o ser em potência. Além disso, é discutível se pré-embriões são seres individualizáveis ou apenas células totipotentes das quais podem vir a surgir nenhum, um ou mais indivíduos. Contudo, o direito à pesquisa é um direito inquestionável. Ora, para que se proíba a pesquisa científica é preciso uma razão imponente. Pesquisadores, por exemplo, não podem violar direitos humanos. Porém, não há consenso de que embriões tenham algum tipo de direito, quanto mais direitos humanos como o direito à vida. Logo, não é razoável proibir de forma absoluta a pesquisa com embriões de laboratório, violando com isso o direito incontroverso à liberdade de pesquisa, sob o argumento de que se está protegendo o direito, todavia controverso, de um ser cujo estatuto biológico e moral é patentemente indeterminado e dificilmente inteligível.
Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration
by Gines Viscor
BACKGROUND:
Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well... more
BACKGROUND:
Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilize hematopoietic stem cells (HSC) and increase their presence in peripheral circulation.
METHODS:
Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposure consisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure.
RESULTS:
There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli.
CONCLUSION:
Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.
Nas fronteiras do" humano": os debates britânico e brasileiro sobre a pesquisa com embriões
Mana, 2007
Com o advento das técnicas de fertilização in vitro no final da década de 70, abriu-se um debate mundial sobre o... more Com o advento das técnicas de fertilização in vitro no final da década de 70, abriu-se um debate mundial sobre o estatuto do embrião produzido em laboratório, assim como sua manipulação experimental na pesquisa científica. O objetivo do artigo é analisar comparativamente dois destes debates no âmbito dos parlamentos britânico e brasileiro. O primeiro resultou na Human Fertilisation and Embriology Act de 1990, e o segundo, nas disposições da Lei de Biossegurança de 2005 relativas às células-tronco embrionárias. A análise, partindo da literatura antropológica sobre o tema, pretendeu demonstrar não só a abertura contemporânea das fronteiras do "humano" a uma negociação explicitamente política, como também os principais vetores que vêm conformando tais negociações no caso da pesquisa científica com embriões humanos.
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