A terapia celular no tratamento da isquemia crítica dos membros inferiores Cell therapy for the treatment of critical ischemia of the lower limbs

The authors review the history of the researches on embryonic and umbilical cord vein stem cells, their advantages and disadvantages. They proceed with comments on adult stem cells, their concept, history, sources and role on tissue regenerative processes, mainly on the endothelium. They stress the importance of factors that mobilize the adult stem cells from the bone marrow: cytokines, angyopoietine and other growth factors. The adult stem cells are mobilized as endothelial progenitor cells, which have a common origin with the endothelial cells from the hemangioblasts. The mobilizing factors are activated under hypoxia and promote the homing of the endothelial progenitor cells on the ischemic sites in order to generate the neovasculogenesis, which is accomplished through three possible mechanisms: angiogenesis (new capillaries from sprouts of the existing ones), arteriogenesis (related to collateral circulation) and vasculogenesis (actual new vessels). An appraisal of the literature is made with regard to animal and clinical sets Finally, they stress that adult stem cells, although bearing an enormous potential, still demand a considerable amount of work to become a current therapeutic method. Resumo Os autores fazem um historico sobre as pesquisas com celulastronco embrionarias e do cordao umbilical, suas respectivas vantagens e desvantagens. Seguem com as discussoes sobre celulas-tronco adultas, sua definicao, historico, fontes e participacao nos processos de regeneracao tecidual, particularmente no endotelio. Ressaltam a importância de fatores que mobilizam as celulas-tronco adultas a partir da medula ossea: citocinas, angiopoietinas e outros fatores de crescimento. As celulas-tronco adultas mobilizam-se sob a forma de celulas endoteliais progenitoras, que tem origem comum com as celulas endoteliais a partir dos hemangioblastos. Os fatores de mobilizacao manifestam-se em condicoes de hipoxia e fazem com que as celulas endoteliais progenitoras se localizem nos locais de isquemia para produzir a neovasculogenese, que se faz por tres possiveis mecanismos: a angiogenese (formacao de novos capilares a partir de brotos de capilares ja existentes), a arteriogenese (relacionada a circulacao colateral) e a vasculogenese (vasos realmente novos). Fazem, a seguir, uma analise da literatura relativa a experimentacao animal e aos estudos clinicos. Concluem ressaltando que as celulas-tronco adultas, embora tenham um grande potencial de uso, ainda demandam muito estudo e pesquisa para se firmar como metodo terapeutico. Palavras-chave: terapia celular, celulas tronco, isquemia critica.