Células-tronco de origem hematopoéticas: expansão e perspectivas de uso terapêutico Hematopoietic stem cells: expansion and perspectives for therapeutic use

A célula-tronco hematopoética (CTH) tem um enorme potencial para reconstituir o sistema hematopoético, o que permitiu o desenvolvimento de estratégias de terapias celulares para doenças neoplásicas ou não. Em paralelo com os avanços clínicos, estudos sobre os mecanismos moleculares que levam as células-tronco hematopoéticas a decidir pela autorrenovação, diferenciação ou apoptose têm contribuído para o conhecimento de como controlar a cinética da CTH. Esta revisão tenta descrever como estes novos avanços podem ser utilizados no desenvolvimento de estratégias de expansão das CTHs para uso terapêutico.<br>Hematopoietic stem cells (HSCs) have the potential for reconstituting the hematopoietic system a characteristic that has enabled the development of cell based therapies for neoplastic and non-malignant diseases. In parallel with these clinical advances, elucidation of molecular mechanisms controlling self-renewal, differentiation or apoptosis have contributed to our understanding of the molecular events that control HSC kinetics. This review focuses on how these advances can be translated in new strategies for HSC expansion and their use in therapies

Seleção de doador não aparentado HLA antibodies and donor selection

Apesar da presença de anticorpos anti-HLA em transplantes de órgãos sólidos estar associada à rejeição, essa correlação não havia sido pesquisada em transplante alogênico de células progenitoras hematopoéticas (TCPH). Estudos mais recentes na literatura têm demonstrado que a falência da enxertia no TCPH pode ser mediada por aloanticorpos anti-HLA doador especifico (DSA). A especificidade desses anticorpos pode ser evidenciada pelas técnicas de fase sólida, onde os antígenos HLA únicos são aderidos a pérolas de poliestireno, que permite a realização da prova cruzada virtual. Na presença de DSA, é recomendável selecionar outro doador ou realizar as estratégias de remoção dos anticorpos.In spite of Anti-HLA antibodies being associated to rejection in solid organs transplantation, this correlation has not been well established yet in allogenic bone marrow transplantation.Recent studies in the literature have demonstrated that engraftment failure in hematopoietic cell transplantation (HCT) can be mediated by donor specific anti-HLA antibodies (DSA). These antibodies specificity can be detected by solid-phase techniques, where single HLA antigens are adhered to microbeads, which allows the interpretation of host reactivity by "virtual crossmatch". In the presence of DSA, it is advisable to either search for another donor or remove the antibodies prior to transplantation

Transplante de sangue de cordão umbilical - SCU Umbilical cord blood transplantation

A frequente utilização de sangue de cordão umbilical - SCU como fonte de células- tronco hematopoéticas - CTH, tanto em crianças, como em adultos, que não dispõem de doador na família, tem levado ao estabelecimento da padronização de critérios em sua seleção, objetivando a obtenção de melhores resultados. A escolha da unidade de SCU deve basear-se no número total de células nucleadas e no número de diferenças de antígenos leucocitários humanos (HLA). Diante de uma unidade com celularidade mínima, deve-se considerar a possibilidade da utilização de duplo cordão. Frente a mais de uma unidade com características semelhantes, a realização da contagem de células CD34 e da compatibilidade ABO, assim como a qualidade e a rapidez para obtenção da unidade, podem definir a escolha.<br>The frequent use of umbilical cord blood as the source of hematopoietic stem cells, both in children and adults who do not have related donors, has led to the establishment of a better standardization of selection criteria aiming at improving the results. The choice of the umbilical cord blood unit should be based on the total number of nucleated cells and the number of differences in the human leukocyte antigen (HLA) system. When a unit has minimal cellularity, the use of a double cord blood transplant should be considered. When two or more units have similar characteristics, the choice may be determined by the CD34 count, ABO compatibility and the quality and speed to obtain the unit

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients

Background. Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods. With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. Results. We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. Conclusions. Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation

Sob o signo neoliberal: as relações internacionais da América Latina

As relações internacionais da América Latina são vistas sob o ângulo da transição da diplomacia do desenvolvimento para a diplomacia neoliberal. Os estudos de relações internacionais, particularmente no Brasil e na Argentina, fundamentam a interpretação do autor sobre benefícios e malogros do paradigma neoliberal, visto como uma opção ideológica. A noção de Estado logístico é sugerida como alternativa estratégica ao Estado normal.<br>In this article, international relations in Latin America are analysed through the viewpoint of the transition from a diplomacy of development to a neoliberal model. Studies in International Relations as a discipline, especially those carried out in Brazil and Argentina, are the basis for the author's interpretation about benefits and failures of the neoliberal paradigm, understood as an ideological option. The author forwards the notion of Logistic State as a strategic alternative to the Normal State