Fabíola Schons Meyer

Intravenous vs intraperitoneal mesenchymal stem cells administration: What is the best route for treating experimental colitis?

AIMnTo investigate the therapeutic effects of mesenchymal stem cells (MSCs) transplanted intraperitoneally and intravenously in a murine model of colitis.nnnMETHODSnMSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were analyzed according to morphology, cellular differentiation potential, and surface molecular markers. Experimental acute colitis was induced in C57BL/6 mice by oral administration of 2% dextran sulfate sodium (DSS) in drinking water ad libitum from days 0 to 7. Colitis mice were treated with 1 × 10(6) MSCs via intraperitoneal or intravenous injection on days 2 and 5. The disease activity index was determined daily based on the following parameters: weight loss, stool consistency and presence of blood in the feces and anus. To compare morphological and functional differences in tissue regeneration between different MSC injection modalities, mice were euthanized on day 8, and their colons were examined for length, weight, and histopathological changes. Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling assay.nnnRESULTSnIntravenous infusion of MSCs was more effective than intraperitoneal treatment (P < 0.001) in reducing the clinical and histopathologic severity of colitis, which includes weight loss, diarrhea and inflammation. An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells. This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)]; and by the up-regulation of anti-inflammatory cytokines (IL-10 and IL-4). Intravenous transplantation also induced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs, which did not occur with intraperitoneal transplantation (P = 0.006). An increase in apoptotic T cells was observed after intravenous, but not intraperitoneal, MSC infusion, suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation (P = 0.027).nnnCONCLUSIONnOur results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.

Análise morfométrica da carótida de suínos submetidos a angioplastia com ou sem implante de stent de cromo-cobalto

Background: Intimal hyperplasia is the most common delayed response to angioplasty. The use of cobalt-chromium stents is well studied in the coronary circulation; however, there are few studies on their use in the carotid and peripheral circulation. Objective: To analyze the intimal reaction in a swine carotid artery undergoing simple angioplasty and angioplasty followed by implantation of cobalt-chromium stent. Materials and methods: We carried out angioplasty in the right common carotid artery and angioplasty with cobalt-chromium stent in the left common carotid artery in eight swine. Four weeks later, all animals were sacrificed for arterial tissue sampling and preparation of histological slides. Slide images were scanned and analyzed using a digital morphometry program. Statistical analysis was performed by mean values and standard deviations of the areas in each group, using the Students t test. A p value of < 0.05 was considered significant. Results: Angioplasty with cobalt-chromium stent implantation resulted in a higher degree of hyperplasia compared with simple angioplasty. The difference was statistically significant when the lumen area, the internal elastic lamina area, and the external elastic lamina area were compared between the two groups. No statistically significant difference was found when the media layers of both groups were compared. Conclusion: Cobalt-chromium stent implantation resulted in more intimal hyperplasia than simple angioplasty, however the stent was not enough to reduce the arterial lumen.

Cell therapy in the treatment of bronchiolitis obliterans in a murine model

OBJECTIVEnTo evaluate the importance of stem cells derived from adipose tissue in reducing graft inflammation in a murine model of allogeneic heterotopic tracheal transplant.nnnMETHODSnWe performed a heterotopic tracheal allografting in dorsal subcutaneous pouch and systemically injected 5x105 mesenchymal stem cells derived from adipose tissue. The animals were divided into two groups according to the time of sacrifice: T7 and T21. We also carried out histological analysis and digital morphometry.nnnRESULTSnThe T7 animals treated with cell therapy had median obstructed graft area of 0 versus 0.54 of controls (p = 0.635). The treated T21 subjects had median obstructed graft area of 0.25 versus 0 in controls (p = 0.041).nnnCONCLUSIONnThe systemically injected cell therapy in experimental murine model of bronchiolitis obliterans did not reduce the severity of the allograft inflammation in a statistically significant way in seven days; Conversely, in 21 days, it increased the allograft inflammatory process.

Histological analysis of cobalt–chromium stents with and without Camouflage® polymer coating: experimental porcine carotid artery model:

This study evaluated the arterial response to cobalt–chromium stents with and without polymer coating (Camouflage®, Hemoteq AG, Wuerselen, Germany) implanted in pigs. Cobalt–chromium balloon-expandable stents (4 × 16 mm) were implanted in the common carotid arteries of nine pigs. Histological analysis of endothelialization, inflammation and injury was performed one month later. All stents were successfully deployed, and all but one animal survived the 30 study days. All arteries were patent. Endothelialization was nearly complete in most sections of all carotid stents in both groups. There were mild inflammatory infiltrate and mild-to-moderate injury, which were associated with the stent shafts and not significantly different between groups. Our findings suggest that, in porcine carotid arteries, the histological response to balloon-expandable cobalt–chromium stents coated with polymer (Camouflage®, Hemoteq AG) is similar to the response to non-coated cobalt–chromium stents.

O modelo experimental de carcinogênese gástrica induzido por n-methyl-n-nitrosourea em ratos F344 e camundongos C3H é válido para os ratos Wistar?

INTRODUCAO: O N-metil-N-nitrosourea (MNU) tem acao cancerigena direta, induzindo tumores em varias especies em uma variedade de orgaos, incluindo o estomago de ratos. Tratamento do MNU na agua de beber por 25-42 semanas, seletivamente, induz carcinoma gastrico glandular de ratos F344 e camundongos C3H. OBJETIVO: Estabelecer um modelo experimental para inducao seletiva de câncer no estomago glandular de ratos Wistar com MNU. METODOS: Um total de 48 ratos Wistar machos com oito semanas, foram utilizados no presente estudo. MNU (Sigma-Aldrich) foi dissolvido em DMSO e liberada agua potavel ad libitum por um periodo variando de 16 a 70 semanas. Apos 16 semanas, quatro ratos foram selecionados aleatoriamente e mortos. Depois, de seis em seis semanas, quatro animais tambem foram mortos ate 70 semanas. RESULTADOS: A taxa de sobrevivencia foi superior a 90%. Ocorreu a inducao de dois adenocarcinomas, um carcinoma espinocelular e um sarcoma. A incidencia de adenocarcinoma gastrico foi de 4,5% (0,5 a 15). CONCLUSOES: O modelo experimental de carcinogenese gastrica em ratos Wistar, utilizando MNU dissolvido na agua, nao mostrou viabilidade pratica neste estudo, devido a baixa taxa de adenocarcinoma gastrico que ocorreu.