Células derivadas da medula óssea no reparo de lesões causadas por infecções parasitárias em camundongos quiméricos

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-05-22T15:50:32Z No. of bitstreams: 1 Carine Machado Azevedo. Células derivadas...2013.pdf: 3773108 bytes, checksum: 06792c88bd29e905b54c5a3d77de8db6 (MD5)Made available in DSpace on 2014-05-22T15:50:32Z (GMT). No. of bitstreams: 1 Carine Machado Azevedo. Células derivadas...2013.pdf: 3773108 bytes, checksum: 06792c88bd29e905b54c5a3d77de8db6 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilA contribuição das células de medula óssea na regeneração de tecidos não hematopoiéticos tem sido intensamente investigada desde a descoberta de células-tronco multipotentes neste órgão. Estudos prévios tem demonstrado que células derivadas da medula óssea podem contribuir para a formação de novos hepatócitos e cardiomiócitos. No presente estudo avaliamos a participação endógena das células-tronco de medula óssea no processo de reparo de lesões teciduais na fase crônica da doença de Chagas e esquistossomose experimentalmente induzidas. Para isso, camundongos quiméricos de medula óssea foram gerados após irradiação com dose letal e posterior reconstituição com células de medula óssea provenientes de camundongos transgênicos para a proteína fluorescente verde (GFP). Um mês após a reconstituição, as quimeras foram infectadas pelo T. cruzi ou S. mansoni. Animais quiméricos saudáveis foram mantidos como controles. Camundongos foram eutanasiados em diferentes períodos para análise morfológica, morfométrica e de marcadores específicos através de imunofluorescência do coração e músculo esquelético ou fígado de acordo com o grupo. As infecções por S. mansoni e T. cruzi causaram a mobilização de diferentes populações celulares para o sangue periférico, tais como monócitos, células-tronco hematopoiéticas e mesenquimais e progenitores endoteliais. Nos dois modelos estudados, observamos um aumento no número de células GFP+ após estímulo lesivo nos tecidos analisados. No modelo de doença de Chagas, há um aumento da expressão de MCP-1, 2 e 3 e SDF-1 no coração e músculo esquelético em comparação com animais não infectados, o que pode contribuir para o recrutamento destas células. As células GFP+ contribuem tanto para a formação da lesão, compondo o infiltrado inflamatório, como para a regeneração tecidual através da formação de miofibras, cardiomiócitos, hepatócitos e vasos sanguíneos. As poucas células GFP+ encontradas nos tecidos de camundongos quimeras normais não possuíam morfologia de células parenquimatosas. Concluímos que a medula óssea pode contribuir para a regeneração dos tecidos lesados através de células-tronco ou progenitores que originam células dos músculos cardíaco e esquelético, hepatócitos e vasos sangüíneos.The contribution of bone marrow cells in non-hematopoietic tissue regeneration has been intensely investigated since the discovery of multipotent stem cells in this organ. Previous studies have shown that bone marrow derived cells may contribute to the formation of new hepatocytes and cardiomyocytes. In the present study, we evaluated the participation of endogenous bone marrow stem cells in the repair of tissue injury in experimentally induced chronic phases of Chagas disease and schistosomiasis. For this purpose, chimeric mice were generated from bone marrow after a lethal irradiation dose and subsequent reconstitution with bone marrow cells from green fluorescent protein (GFP) transgenic mice. A month after reconstitution, chimeras were either infected with Trypanosoma cruzi or Schistosoma mansoni, or kept healthy as controls. Mice were euthanized at different time points for histological, morphometric and specific markers by immunofluorescence analysis in heart and skeletal muscle or in the liver, according to the group. Infections caused by S. mansoni and T. cruzi resulted in the mobilization of different cell populations to the peripheral blood, including monocytes, hematopoietic and mesenchymal stem cells, and endothelial progenitors. In the two models studied, we observed an increase in the number of GFP+ cells after injury stimulus in the tissues analyzed. In the model of Chagas disease, there is an increased expression of MCP-1, 2, 3 and SDF-1 in heart and skeletal muscle compared to uninfected animals, which can contribute to the recruitment of these cells. The GFP+ cells both contribute to lesion formation, comprised of inflammatory infiltrate, as well as tissue regeneration by forming myofibers, cardiomyocytes, hepatocytes and blood vessels. The few GFP+ cells found in control chimera mice tissue lacked parenchymal cell morphology. We concluded that bone marrow may contribute to the regeneration of injured tissues through stem or progenitor cells, which gives rise cardiac and skeletal muscle cells, hepatocytes and blood vessels

Alterações induzidas em biomphalaria glabrata (Say, 1818) após tentativas de estimulação artificial do seu sistema interno de defesa

Submitted by Repositório Arca ([email protected]) on 2019-07-08T17:27:34Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-09T18:52:23Z (GMT) No. of bitstreams: 2 Carine Machado Azevedo 2006.pdf: 31683980 bytes, checksum: ef126d1655e5f61464776fe40ad8a16a (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-07-09T18:52:23Z (GMT). No. of bitstreams: 2 Carine Machado Azevedo 2006.pdf: 31683980 bytes, checksum: ef126d1655e5f61464776fe40ad8a16a (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2006CNPqUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.A Biomphalaria glabrata pode responder de diferentes maneiras à penetração dos miracídios de Schistosoma mansoni. conforme os variados graus de resistência existentes entre as diferentes linhagens. Sabe-se que o caráter resistência/susceptibilidade é determinado geneticamente, sendo a resistência dominante sobre a susceptibilidade. Por outro lado, caramujos muito susceptíveis de início (como os da linhagem FS) podem vir a exibir um padrão de eliminação de cercárias e de reações histopatológicas sugestivo da presença de alta resistência, com o decorrer do tempo de infecção. Esta observação sugere que a B. glabrata pode desenvolver um tipo de imunidade adaptativa. O presente trabalho teve como objetivo estudar o comportamento da infecção pelo S.mansoni em B. glabrata após tentativa de estimulação artificial do Sistema Interno de Defesa destes caramujos. Para isso, caramujos foram previamente inoculados (Grupo I) com miracídios irradiados; tratados com antígenos do S. mansoni (Grupo liA) ou de um outro parasito a ele não relacionado, a Capillaria hepatica (Grupo 118); e um outro grupo (Grupo 111) constituído por caramujos infectados e posteriormente tratados com oxamniquina + praziquantel. Em seguida, os animais de todos os grupos foram desafiados com 20 miracídios normais, exceto o último grupo, pois no mesmo não ocorreu a cura esperada. Os animais de todos os grupos foram analisados quanto à emissão de cercarias e sacrificados em diferentes pontos da infecção para exame histopatológico. Nos tecidos dos animais previamente sensibilizados apareceram nódulos de proliferação hemocitária (granulomas) sem elementos parasitários em seu interior, sendo em menor numero e intensidade no grupo inoculado com antígeno de C. hepatica. O aparecimento destes granulomas não evitou o desenvolvimento normal da infecção de prova, a qual ocorreu em vários órgãos sem aparente reação do hospedeiro, com emissão de cercarias, tal como visto nos controles. Os dados indicam que os hemócitos reagem focalmente e que sua mobilização por estimulação antigênica não se transmite ao resto da população hemocitária.Biomphalaria glabrata can react through different pathways to Schistosoma mansoni miracidium penetration, according to the degree of resistance/susceptibility presented by different snail strains, which is a genetically determined character, resistance being dominant..However, it has been observed that previous susceptible snail strain may change its reactive behavior along the course of infection, and later exhibits a pattern of cercarial shedding and histopatopathologicai picture compatible with high resistance. Such observation suggests the possibility of B. glabrata to develop a sort of adaptative immunity face a schistosome infection. To explore on this aspect, the present investigation looked for the behavior of S. mansoni infection in B. glabrata previously subjected to different means of artificial stimulation of its intemal defense system. Snails previously inoculated with irradiated miracidia (Group lA); treated with S. mansoni antigens (Group IIA) or with a non-related parasite antigen (Group IIB) were challenged with 20 viable S. mansoni miracidia, and later looked for cercarial shedding and histopathologic changes at different times from exposition. Nodules of hemocyte accumulations were found at the site of “antigen” injection. These nodules resembled solid granulomas, and were larger and more frequent in snails injected with S. mansoni products as compared to those injected with C. hepatica. However, the presence of such granulomas did not avoid the S. mansoni challenge infection from developing in a similar way as that seen in their controls. The data are indicative that hemocytes are able to proliferate locally when stimulated, such capacity also remaining localized, not being shared by the population of hemocytes located everywhere else within the snail body

Changes induced in Biomphalaria glabrata (Say, 1818) following trials for artificial stimulation of its internal defense system

Biomphalaria glabrata can react through different pathways to Schistosoma mansoni miracidium penetration, according to the degree of resistance/susceptibility presented by different snail strains, which is a genetically determined character, resistance being the dominant feature. However, it has been observed that previous susceptible snail strain may change its reactive behavior along the course of infection, exhibiting later a pattern of cercarial shedding and histopatopathological picture compatible with high resistance. Such observation suggests the possibility of B. glabrata to develop a sort of adaptative immunity face a schistosome infection. To explore on this aspect, the present investigation looked for the behavior of S. mansoni infection in B. glabrata previously subjected to different means of artificial stimulation of its internal defense system. Snails previously inoculated with irradiated miracídia (Group I); treated with S. mansoni antigens (Group II) or with a non-related parasite antigen (Group III) were challenged with 20 viable S. mansoni miracidia, and later looked for cercarial shedding and histopathologic changes at different times from exposition. Nodules of hemocyte accumulations were found at the site of antigen injection. These nodules resembled solid granulomas, and were larger and more frequent in snails injected with S. mansoni products as compared to those injected with Capillaria hepatica . However, the presence of such granulomas did not avoid the S. mansoni challenge infection from developing in a similar way as that seen in controls. The data are indicative that hemocytes are able to proliferate locally when stimulated, such capacity also remaining localized, not being shared by the population of hemocytes located elsewhere within the snail body

Changes induced in Biomphalaria glabrata (Say, 1818) following trials for artificial stimulation of its internal defense system

Biomphalaria glabrata can react through different pathways to Schistosoma mansoni miracidium penetration, according to the degree of resistance/susceptibility presented by different snail strains, which is a genetically determined character, resistance being the dominant feature. However, it has been observed that previous susceptible snail strain may change its reactive behavior along the course of infection, exhibiting later a pattern of cercarial shedding and histopatopathological picture compatible with high resistance. Such observation suggests the possibility of B. glabrata to develop a sort of adaptative immunity face a schistosome infection. To explore on this aspect, the present investigation looked for the behavior of S. mansoni infection in B. glabrata previously subjected to different means of artificial stimulation of its internal defense system. Snails previously inoculated with irradiated miracídia (Group I); treated with S. mansoni antigens (Group II) or with a non-related parasite antigen (Group III) were challenged with 20 viable S. mansoni miracidia, and later looked for cercarial shedding and histopathologic changes at different times from exposition. Nodules of hemocyte accumulations were found at the site of antigen injection. These nodules resembled solid granulomas, and were larger and more frequent in snails injected with S. mansoni products as compared to those injected with Capillaria hepatica. However, the presence of such granulomas did not avoid the S. mansoni challenge infection from developing in a similar way as that seen in controls. The data are indicative that hemocytes are able to proliferate locally when stimulated, such capacity also remaining localized, not being shared by the population of hemocytes located elsewhere within the snail body

Intramyocardial transplantation of cardiac mesenchymal stem cells reduces myocarditis in a model of chronic Chagas disease cardiomyopathy

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-10-08T16:56:49Z No. of bitstreams: 1 Silva D N Intramyocardial....pdf: 1440616 bytes, checksum: 8df954e30732cb7c8f805b3f571d2e66 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-10-08T16:57:02Z (GMT) No. of bitstreams: 1 Silva D N Intramyocardial....pdf: 1440616 bytes, checksum: 8df954e30732cb7c8f805b3f571d2e66 (MD5)Made available in DSpace on 2014-10-08T17:42:59Z (GMT). No. of bitstreams: 1 Silva D N Intramyocardial....pdf: 1440616 bytes, checksum: 8df954e30732cb7c8f805b3f571d2e66 (MD5) Previous issue date: 2014Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilINTRODUCTION: New therapeutic options are necessary for patients with chronic Chagas disease, a leading cause of heart failure in Latin American countries. Stem cell therapy focused on improving cardiac function is a promising approach for treating heart disease. Here, we evaluated the therapeutic effects of cardiac mesenchymal stem cells (CMSCs) in a mouse model of chronic Chagas disease. METHODS: CMSCs were isolated from green fluorescent protein (GFP) transgenic C57BL/6 mouse hearts and tested for adipogenic, osteogenic, chondrogenic, endothelial, and cardiogenic differentiation potentials evaluated by histochemical and immunofluorescence techniques. A lymphoproliferation assay was performed to evaluate the immunomodulatory activity of CMSCs. To investigate the therapeutic potential of CMSCs, C57BL/6 mice chronically infected with Trypanosoma cruzi were treated with 106 CMSCs or saline (control) by echocardiography-guided injection into the left ventricle wall. All animals were submitted to cardiac histopathological and immunofluorescence analysis in heart sections from chagasic mice. Analysis by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed in the heart to evaluate the expression of cytokines involved in the inflammatory response. RESULTS: CMSCs demonstrated adipogenic, osteogenic, and chondrogenic differentiation potentials. Moreover, these cells expressed endothelial cell and cardiomyocyte features upon defined stimulation culture conditions and displayed immunosuppressive activity in vitro. After intramyocardial injection, GFP+ CMSCs were observed in heart sections of chagasic mice one week later; however, no observed GFP+ cells co-expressed troponin T or connexin-43. Histopathological analysis revealed that CMSC-treated mice had a significantly decreased number of inflammatory cells, but no reduction in fibrotic area, two months after treatment. Analysis by qRT-PCR demonstrated that cell therapy significantly decreased tumor necrosis factor-alpha expression and increased transforming growth factor-beta in heart samples. CONCLUSIONS: We conclude that the CMSCs exert a protective effect in chronic chagasic cardiomyopathy primarily through immunomodulation

Phagocytosis is inhibited by autophagic induction in murine macrophages.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-05-30T16:56:31Z No. of bitstreams: 1 Lima JGB Phagocytosis is....pdf: 836654 bytes, checksum: 7d68ca3472c63cc339313f0c944bf60f (MD5)Made available in DSpace on 2014-05-30T16:56:31Z (GMT). No. of bitstreams: 1 Lima JGB Phagocytosis is....pdf: 836654 bytes, checksum: 7d68ca3472c63cc339313f0c944bf60f (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilRecent studies have demonstrated that communication takes place between the autophagic and phagocytic pathways, indicating that the convergence of these two pathways plays an important role in the innate immune response against intracellular microbes. The present study investigated the effect of autophagic induction on the phagocytic capacity of murine macrophages. Autophagy induced by physiological and pharmacological means was shown to reduce the phagocytic capacity of murine macrophages, regardless of cell origin or the nature of the phagocytosed particles themselves. This autophagic inhibitory effect on phagocytosis was shown to be an early and reversible event that results in no loss of cell viability. Furthermore, the data presented herein demonstrate that the induction of autophagy does not affect a macrophage’s capacity to recognize and bind to particles, indicating that autophagy does not inhibit the particle recognition process, even though particle internalization is suppressed. The findings herein support the notion that phagocytosis and autophagy may be interdependent and complementary processe

Bone marrow-derived cells migrate to the liver and contribute to the generation of different cell types in chronic Schistosoma mansoni infection.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-12T11:49:09Z No. of bitstreams: 1 Azevedo CM Bone marrow-derived....pdf: 3729658 bytes, checksum: 883b520fbb9c3e919e95fff44fcaeb9e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-12T12:10:32Z (GMT) No. of bitstreams: 1 Azevedo CM Bone marrow-derived....pdf: 3729658 bytes, checksum: 883b520fbb9c3e919e95fff44fcaeb9e (MD5)Made available in DSpace on 2016-05-12T12:10:32Z (GMT). No. of bitstreams: 1 Azevedo CM Bone marrow-derived....pdf: 3729658 bytes, checksum: 883b520fbb9c3e919e95fff44fcaeb9e (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilThe main pathogenic event caused by Schistosoma mansoni infection is characterized by a granulomatous inflammatory reaction around parasite eggs and fibrosis in the liver. We have previously shown that transplantation of bone marrow cells (BMC) promotes a reduction in liver fibrosis in chronically S. mansoni-infected mice. Here we investigated the presence and phenotype of bone marrow-derived cells in livers of S. mansoni-infected mice. During the chronic phase of infection, C57BL/6 mice had an increased number of circulating mesenchymal stem cells and endothelial progenitor cells in the peripheral blood when compared to uninfected controls. In order to investigate the fate of BMC in the liver, we generated bone marrow chimeric mice by transplanting BMC from transgenic green fluorescent protein (GFP) mice into lethally irradiated wild-type C57BL/6 mice. S. mansoni-infected chimeric mice did not demonstrate increased mortality and developed similar liver histopathological features, when compared to wild-type S. mansoni-infected mice. GFP(+) bone marrow-derived cells were found in the liver parenchyma, particularly in periportal regions. CD45(+)GFP(+) cells were found in the granulomas. Flow cytometry analysis of digested liver tissue characterized GFP(+) cells as lymphocytes, myeloid cells and stem cells. GFP(+) cells were also found in areas of collagen deposition, although rare GFP(+) cells expressed the myofibroblast cell marker α-SMA. Additionally GFP(+) endothelial cells (co-stained with von Willebrand factor) were frequently observed, while BMC-derived hepatocytes (GFP(+) albumin(+) cells) were sparsely found in the liver of chimeric mice chronically infected with S. mansoni. In conclusion, BMC are recruited to the liver during chronic experimental infection with S. mansoni and contribute to the generation of different cell types involved, not only in disease pathogenesis, but possibly in liver regeneration and repai

Early transplantation of bone marrow mononuclear cells promotes neuroprotection and modulation of inflammation after status epilepticus in mice by paracrine mechanisms.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-19T17:24:00Z No. of bitstreams: 1 Leal MMT Early....pdf: 781614 bytes, checksum: d9ce1f5869c3b92b18bd5f5dc7f0b8e9 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-19T17:50:20Z (GMT) No. of bitstreams: 1 Leal MMT Early....pdf: 781614 bytes, checksum: d9ce1f5869c3b92b18bd5f5dc7f0b8e9 (MD5)Made available in DSpace on 2015-05-19T17:50:20Z (GMT). No. of bitstreams: 1 Leal MMT Early....pdf: 781614 bytes, checksum: d9ce1f5869c3b92b18bd5f5dc7f0b8e9 (MD5) Previous issue date: 2014Hospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilStatus epilepticus (SE) is a severe clinical manifestation of epilepsy associated with intense neuronal loss and inflammation, two key factors involved in the pathophysiology of temporal lobe epilepsy. Bone marrow mononuclear cells (BMMC) attenuated the consequences of pilocarpine-induced SE, including neuronal loss, in addition to frequency and duration of seizures. Here we investigated the effects of BMMC transplanted early after the onset of SE in mice, as well as the involvement of soluble factors produced by BMMC in the effects of the cell therapy. Mice were injected with pilocarpine for SE induction and randomized into three groups: transplanted intravenously with 1 × 10(7) BMMC isolated from GFP transgenic mice, injected with BMMC lysate, and saline-treated controls. Cell tracking, neuronal counting in hippocampal subfields and cytokine analysis in the serum and brain were performed. BMMC were found in the brain 4 h following transplantation and their numbers progressively decreased until 24 h following transplantation. A reduction in hippocampal neuronal loss after SE was found in mice treated with live BMMC and BMMC lysate when compared to saline-treated, SE-induced mice. Moreover, the expression of inflammatory cytokines IL-1ß, TNF-α, IL-6 was decreased after injection of live BMMC and to a lesser extent, of BMMC lysate, when compared to SE-induced controls. In contrast, IL-10 expression was increased. Analysis of markers for microglia activation demonstrated a reduction of the expression of genes related to type 1-activation. BMMC transplantation promotes neuroprotection and mediates anti-inflammatory effects following SE in mice, possibly through the secretion of soluble factors