Terapia celular para acidente vascular cerebral isquêmico: esperança ou panacéia?
Hospital Pró-Cardíaco, Universidade Federal do Rio de Janeiro e Instituto do Milênio de Bioengenharia Tecidual - Rio de Janeiro - RJ
Células-tronco são definidas como células que mantêm a capacidade de auto-replicação e diferenciação em múltiplas linhagens1. Estas células, presentes em proporções variáveis em órgãos adultos, teoricamente podem dar origem a qualquer tecido vivo de um organismo. Embora o conceito de transplante de células-tronco não seja novo, vem tendo um interesse crescente com este tipo de terapia, após a demonstração de que a medula óssea adulta poderia fornecer uma quantidade suficiente de células multipotentes para um transplante autólogo2. Entretanto, o otimismo relacionado a qualquer novo tratamento deve ser avaliado com cautela.
Exames de neuroimagem para avaliação da evolução do AVC nesta paciente também foram realizados e incluíram ressonância magnética, cintilografia (SPECT) e tomografia computadorizada com emissão de pósitrons (PET) cerebral. Tais imagens também devem ser interpretadas no contexto da evolução natural do AVC isquêmico agudo. O padrão mais freqüente em pacientes com AVC agudo é que a área de necrose (
A pesquisa com células-tronco abre uma avenida fascinante em doenças neurológicas. Entretanto muito ainda precisa ser esclarecido: estudos de ciência básica devem elucidar os mecanismos exatos pelos quais a terapia celular é capaz de recuperar déficits relacionados ao AVC; estudos clínicos em seres humanos, controlados e randomizados serão necessários para avaliação dos pacientes submetidos ao transplantes com células-tronco da medula óssea comparados àqueles com história natural do AVC isquêmico. A avaliação cuidadosa da segurança deste tipo de procedimento também é fundamental, uma vez que um risco aumentado de trombose no sítio de injeção e desenvolvimento de focos epileptogênicos são ainda uma preocupação à medida que mais pacientes são estudados. Os autores do estudo mencionado devem ser parabenizados tanto pela experiência pioneira quanto pelos comentários realísticos, sendo que os resultados comparativos da fase I são ansiosamente esperados. A terapia celular provavelmente não será uma panacéia para o tratamento de doenças neurológicas, mas a esperança do sucesso deve estimular a continuidade da pesquisa científica nesta área. Nossos pacientes merecem isso.
1. Körbling M, Estrov Z. Adult stem cells for tissue repair - a new therapeutic concept? N Engl J Med. 2003;349:570-82.
2. Jiang Y, Jahagirdar BN, Reinhardt RL et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41-9.
3. Oliveira-Filho J, Silva SCS, Trabuco CC et al. Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology. 2003;61:1047–51.
4. Baracchini C, Manara R, Ermani M, Meneghetti G. The quest for early predictors of stroke evolution. Can TCD be a guiding light? Stroke. 2000;31:2942-7.
5. Alexandrov AV, Felberg RA, Demchuk AM et al. Deterioration following spontaneous improvement: Sonographic findings in patients with acutely resolving symptoms of cerebral ischemia. Stroke. 2000;31:915-9.
6. Schwamm LH, Koroshetz WJ, Sorensen AG et al. Time course of lesion development in patients with acute stroke. Serial diffusion- and hemodynamic-weighted magnetic resonance imaging. Stroke. 1998;29:2268-76.
7. Lecouvet FE, Duprez TPJ, Raymackers JM, Peeters A, Cosnard G. Resolution of early diffusion-weighted and FLAIR MRI abnormalities in a patient with TIA. Neurology. 1999; 52:1085–7.
8. Krueger K, Kugel H, Grond M, Thiel A, Maintz D, Lackner K. Late resolution of diffusion-weighted MRI changes in a patient with prolonged reversible ischemic neurological deficit after thrombolytic therapy. Stroke. 2000;31:2715-8.
Hans Fernando Rocha Dohmann Av. Nossa Senhora de Copacabana, 2/602 22010-120 – Rio de Janeiro – RJ E-mail:
Recebido em 21/12/04
Aceito em 10/01/05
Stem cells for ischemic stroke: hope or panacea?
Hospital Pró-Cardíaco, Universidade Federal do Rio de Janeiro e Instituto do Milênio de Bioengenharia Tecidual - Rio de Janeiro - RJ - Brazil
Stem cells are defined as cells that retain the capability to replicate and differentiate into multiple cell lineages1. These cells, which are present in variable proportions in the adult organs, could theoretically generate any living tissue of a particular organism. Although the concept of (fetal) stem cell transplantation is not new, considerable interest has arisen since the demonstration of such cells in the adult bone marrow, which could potentially provide enough cells for autologous transplantation2. However, optimism that comes with any new therapy must be viewed with tempered caution.
In the issue of January/06 of the
Neuroimaging surrogate endpoints for stroke outcome are also presented in the case report, including MRI, SPECT and PET. These should also be interpreted in the context of the natural history of stroke on neuroimaging. The most frequent pattern in acute stroke patients is that of an area of necrosis ("core") surrounded an area of hypoperfusion that is ischemic but still viable ("penumbra")6. This pattern usually persists for 24 hours, where cells located in the penumbra progressively die and the core expands approximately to the area of the initial hypoperfusion6. Improvement in the initial hypoperfusion is expected in most stroke patients over time, and even diffusion abnormalities have been shown to recover in select cases7,8. Regional improvement in metabolism by PET was suggested in this report, but some spontaneous improvement is expected in stroke patients, and the lack of quantitative data somewhat limits the conclusions.
Stem cell research is an exciting new avenue in neurological diseases. Much is still needed: basic science studies should clarify the exact mechanisms by which stem cells improve stroke-related deficits; and clinical studies with control groups should compare natural history with treatment groups. Safety also requires more thorough evaluation, as risk of thrombosis at the site of injection and long-term epilepsy are still concerns as more patients are studied. The authors are to be congratulated for their pioneering experience as well as for their realistic comments. Future comparative data from their phase I study is anxiously waited. Stem cells will probably not be a panacea for neurological diseases, but hope should foster sound scientific research. Our patients deserve it.
1. Körbling M, Estrov Z. Adult stem cells for tissue repair - a new therapeutic concept? N Engl J Med. 2003;349:570-82.
2. Jiang Y, Jahagirdar BN, Reinhardt RL et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41-9.
3. Oliveira-Filho J, Silva SCS, Trabuco CC et al. Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology. 2003;61:1047–51.
4. Baracchini C, Manara R, Ermani M, Meneghetti G. The quest for early predictors of stroke evolution. Can TCD be a guiding light? Stroke. 2000;31:2942-7.
5. Alexandrov AV, Felberg RA, Demchuk AM et al. Deterioration following spontaneous improvement: Sonographic findings in patients with acutely resolving symptoms of cerebral ischemia. Stroke. 2000;31:915-9.
6. Schwamm LH, Koroshetz WJ, Sorensen AG et al. Time course of lesion development in patients with acute stroke. Serial diffusion- and hemodynamic-weighted magnetic resonance imaging. Stroke. 1998;29:2268-76.
7. Lecouvet FE, Duprez TPJ, Raymackers JM, Peeters A, Cosnard G. Resolution of early diffusion-weighted and FLAIR MRI abnormalities in a patient with TIA. Neurology. 1999; 52:1085–7.
8. Krueger K, Kugel H, Grond M, Thiel A, Maintz D, Lackner K. Late resolution of diffusion-weighted MRI changes in a patient with prolonged reversible ischemic neurological deficit after thrombolytic therapy. Stroke. 2000;31:2715-8.
Hans Fernando Rocha Dohmann Av. Nossa Senhora de Copacabana, 2/602 22010-120 – Rio de Janeiro – RJ - Brazil E-mail:
Received on 12/21/04
Accepted on 01/10/05