Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis.

BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously. RESULTS: Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1ß decreased, while VEGF and TGF-ß did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas. CONCLUSIONS: Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.

Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury.

The objective of our study was to evaluate the therapeutic potential of bone marrow mesenchymal stromal cells (MSC) in a rat model of severe chronic liver injury. Fourteen female Wistar rats were fed exclusively an alcoholic liquid diet and received intraperitoneal injections of carbon tetrachloride every other day during 15 weeks. After this period, eight animals (MSC group) had 1 x 10(7) cells injected into the portal vein while six animals (placebo group) received vehicle. Blood analysis was performed to evaluate alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin before cell therapy and 1 and 2 months after cell or placebo infusion. Fibrosis was evaluated before and 1 month after cell or placebo injection by liver biopsies. Two months after cell delivery, animals were sacrificed and histological analysis of the livers was performed. Fibrosis was quantified by histomorphometry. Biopsies obtained before cell infusion showed intense collagen deposition and septa interconnecting regenerative nodules. One month after cell injection, this result was unaltered and differences in fibrosis quantification were not found between MSC and placebo groups. ALT and AST returned to normal values 2 weeks after cell or placebo infusion, without significant differences between experimental groups. Two months after cell or placebo injection, albumin had also returned to normal values and histological results were maintained, again without differences between MSC and placebo groups. Therefore, under our experimental conditions, MSC were unable to reduce fibrosis or improve liver function in a rat model of severe chronic liver injury.

[Procedural memory and brain SPECT: blood flow evaluation in the cerebellum and pre-frontal cortex during a visuo-motor task]. / Memória de procedimentos e SPECT cerebral: avaliação de fluxo sanguíneo cerebelar e em córtex pré-frontal durante uma tarefa visuo-motora.

The objective of the present study was to evaluate the cerebral blood flow in the cerebellar (4 sub-regions) and pre-frontal cortex, when subjects were in rest and during a motor task performance. The sample consisted of 8 healthy subjects, male or female, between 23 and 36 of age. The visuo-motor task - implicit memory - requires the subjects to navigate and swerve a graphic submarine from missiles that run on the screen. Semi-quantitative analysis with brain SPECT (99mTc-ECD) was used to evaluate regional perfusion. The results revealed an increased activity in all areas of interest during motor task. In conclusion, four sub-regions of cerebellar cortex and both pre-frontal hemispheres showed a simultaneous activation during task. Moreover, our findings suggest as seen in previous experiments that the central nervous system operates in a parallel fashion, in order to integrate sensory and motor information.

Memória de procedimentos e SPECT cerebral: avaliação de fluxo sanguíneo cerebelar e em córtex pré-frontal durante uma tarefa visuo-motora / Procedural memory and brain SPECT: blood flow evaluation in the cerebellum and pre-frontal cortex during a visuo-motor task

O objetivo deste estudo foi avaliar o fluxo sanguíneo cerebral no córtex cerebelar (4 sub-regiões) e no córtex pré-frontal, em repouso e durante uma tarefa motora. A amostra foi composta por 8 sujeitos saudáveis, ambos os sexos, entre 23 e 36 anos. O grupo foi submetido a tarefa visuo-motora (memória implícita) que consistia na ação de desviar um submarino de supostas minas que percorriam a tela do monitor. Para avaliar a perfusão, foi utilizado o método de análise semi-quantitativa para imagens de SPECT cerebral - 99mTc-ECD. Os resultados evidenciaram aumento de atividade nas áreas de interesse durante a realização da tarefa. Em conclusão, quatro sub-regiões do córtex cerebelar e ambos os hemisférios do córtex pré-frontal apontaram uma ativação simultânea durante a tarefa. Ainda, e conforme estudos prévios, nossos resultados sugerem um modo de operação em paralelo do sistema nervoso central, no intuito de integrar uma informação sensorial e motora.

The objective of the present study was to evaluate the cerebral blood flow in the cerebellar (4 sub-regions) and pre-frontal cortex, when subjects were in rest and during a motor task performance. The sample consisted of 8 healthy subjects, male or female, between 23 and 36 of age. The visuo-motor task _ implicit memory _ requires the subjects to navigate and swerve a graphic submarine from missiles that run on the screen. Semi-quantitative analysis with brain SPECT (99mTc-ECD) was used to evaluate regional perfusion. The results revealed an increased activity in all areas of interest during motor task. In conclusion, four sub-regions of cerebellar cortex and both pre-frontal hemispheres showed a simultaneous activation during task. Moreover, our findings suggest as seen in previous experiments that the central nervous system operates in a parallel fashion, in order to integrate sensory and motor information.

Detecção do linfonodo sentinela com injeções periareolar do corante azul patente V e peritumoral do 99MTc-Fitato em carcinoma invasor de mama / Blue dye periareolar and 99MTc-Phytate peritumoral injections in sentinel node localization for invasive breast cancer

Objetivo: verificar o sucesso da localização do linfonodo sentinela (LS) com injeção periareolar de azul patente V em casos de carcinoma de mama, correlacionando-o a variáveis como, idade, tamanho da lesão, resultado da linfocintilografia pré-operatória, localização e grau histopatológico do tumor. A injeção peritumoral de 99mTc-fitato, realizada simultaneamente em toda a amostra - considerada padrão-ouro - permitiu o cálculo da sensibilidade da via periareolar e avaliar se os mesmos LSs eram marcados por ambas as técnicas. Métodos: realizaram-se 54 procedimentos para a biópsia do linfonodo sentinela (BLS) após injeções de 0,1 mCi de 99mTc-fitato, via peritumoral, seguidas de linfocintilografias mamárias, e de 2 mL de azul patente V periareolar. Resultados: as injeções com o corante conseguiram êxito em 53 casos (98,15 por cento) versus 50 (92,59 por cento) no método radioguiado, e no único insucesso do azul patente V também não houve marcação com o 99mTc-fitato. A sensibilidade da injeção periareolar foi de 100 por cento. Entre as variáveis, somente o resultado da linfocintilografia influiu significativamente na marcação do LS por ambos os métodos. Conclusão: a injeção periareolar conseguiu marcar o mesmo LS que a peritumoral, a despeito da localização do tumor. Tal constatação é importante, pois a via periareolar é mais simples, de rápido aprendizado e em lesões impalpáveis dispensa métodos especiais.