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OBJECTIVE: To investigate the effect of adipose tissue-derived mesenchymal stem cell (ASC) administered either systemically or locally in a murine model of bronchiolitis obliterans. RESULTS: When compared to controls, systemic treatment with 106 ASCs on D0 and a second dose on D7 significantly prevented tracheal obliteration 28 days after heterotopic tracheal transplantation (median of 94 vs. 16%; P < 0.01). A single dose tended towards less stenosis than controls, but did not reach statistical significance (28 vs. 94%; P = 0.054). On the contrary, repeated local injection was incapable of preventing tracheal obliteration when compared to a single injection or controls (37 vs. 71 vs. 87%). Two intravenous doses also tended to be better than two local injections (16 vs. 37%; P = 0.058), and were better than a single local dose (16 vs. 71%; P < 0.01). CONCLUSION: A second dose of ASC, given systemically after 7 days, reduces luminal obliteration in a heterotopic tracheal transplantation model in mice, suggesting that ASC can be used to prevent obliterative bronchiolitis after lung transplantation.
Assuntos
Tecido Adiposo/citologia , Bronquiolite Obliterante/prevenção & controle , Células-Tronco Mesenquimais/fisiologia , Traqueia , Animais , Bronquiolite Obliterante/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Traqueia/patologia , Traqueia/fisiopatologia , Traqueia/transplanteRESUMO
Background: Colitis murine models have become essential tools to investigate the molecular and cellular mechanisms that lead to inflammatory bowel disease (IBD), such as ulcerative colitis (UC). DSS-induced colitis model faithfully reproduces many of the clinical presentation and immunological disturbances observed in UC. Notwithstanding mice can show differential susceptibilities and responsiveness to dextran sodium sulfate (DSS), and varying DSS concentration and molecular weights appear to be associated with the severity of inflammation. The aim of this study was to analyze the features of mice induced colitis using different DSS concentrations and molecular weights. Materials, Methods and Results: C57BL/6 mice received 2% of high molecular weight DSS (36 000 - 50 000) in drinking water (HDSS2%) or 5% of the same molecular weight (HDSS5%); other group received 5% of low molecular weight DSS (10 000) (LDSS5%). During the 7 days of DSS administration, animals were observed for weight loss, stool consistency and presence of blood feces to determine the disease activity index (DAI). On day 8, colons were removed, measured and weighed for indirect assessment of inflammation. The tissue samples were processed for histological analysis and blood samples were collected for hematological analysis. Our results demonstrated that HDSS5% group began to show significant clinical signs sta
Background: Colitis murine models have become essential tools to investigate the molecular and cellular mechanisms that lead to inflammatory bowel disease (IBD), such as ulcerative colitis (UC). DSS-induced colitis model faithfully reproduces many of the clinical presentation and immunological disturbances observed in UC. Notwithstanding mice can show differential susceptibilities and responsiveness to dextran sodium sulfate (DSS), and varying DSS concentration and molecular weights appear to be associated with the severity of inflammation. The aim of this study was to analyze the features of mice induced colitis using different DSS concentrations and molecular weights. Materials, Methods and Results: C57BL/6 mice received 2% of high molecular weight DSS (36 000 - 50 000) in drinking water (HDSS2%) or 5% of the same molecular weight (HDSS5%); other group received 5% of low molecular weight DSS (10 000) (LDSS5%). During the 7 days of DSS administration, animals were observed for weight loss, stool consistency and presence of blood feces to determine the disease activity index (DAI). On day 8, colons were removed, measured and weighed for indirect assessment of inflammation. The tissue samples were processed for histological analysis and blood samples were collected for hematological analysis. Our results demonstrated that HDSS5% group began to show significant clinical signs sta
RESUMO
Background: Colitis murine models have become essential tools to investigate the molecular and cellular mechanisms that lead to infl ammatory bowel disease (IBD), such as ulcerative colitis (UC). DSS-induced colitis model faithfully reproduces many of the clinical presentation and immunological disturbances observed in UC. Notwithstanding mice can show differential susceptibilities and responsiveness to dextran sodium sulfate (DSS), and varying DSS concentration and molecular weights appear to be associated with the severity of inflammation. The aim of this study was to analyze the features of mice induced colitis using different DSS concentrations and molecular weights. Materials, Methods and Results: C57BL/6 mice received 2% of high molecular weight DSS (36 000 - 50 000) in drinking water (HDSS2%) or 5% of the same molecular weight (HDSS5%); other group received 5% of low molecular weight DSS (10 000) (LDSS5%). During the 7 days of DSS administration, animals were observed for weight loss, stool consistency and presence of blood feces to determine the disease activity index (DAI). On day 8, colons were removed, measured and weighed for indirect assessment of infl ammation. The tissue samples were processed for histological analysis and blood samples were collected for hematological analysis. Our results demonstrated that HDSS5% group began to show significant clinical signs starting from day 1, HDSS2% on day 2 and LDSS5% on day 3 (P < 0.05). However, from day 3, HDSS5% group presented DAI significantly higher than other groups (P < 0.001). In addition, DSS administration for 7 days was associated with significant (P < 0.05) changes in mice body weight compared to control animals. Group HDSS2% showed a weight loss of 23.8%±3.0, and HDSS5% and LDSS5% groups, presented weight loss of 32.65%±0.0 and 8.7%±1.7, respectively. From day 6, HDSS5% group presented weight loss significantly greater than HDSS2% and LDSS5% groups (P < 0.05). In colon macroscopic analysis, high molecular weight DSS groups showed a significantly macroscopic colon changes (P = 0.001) and hematological parameters alteration (P < 0.005) compared to control group. In histological features of colitis, these groups presented a higher histological score compared to normal colon (P < 0.001), with crypt damage, mucosal ulceration and cell inflammatory infiltration. Mice from group LDSS5% did not present significant macroscopic colon changes, hematological parameters alteration, and histological score compared to control group. Discussion: Results of the present study evidenced that acute colonic mucosal injury induced by DSS is dependent on the concentration and molecular weight of DSS administered in drinking water, and these findings are important consideration for reproducible induction of experimental colitis with this model. Moreover, DSS with high molecular weight and high concentration can initiate a severe colitis, which may not be an appropriate model for studies of therapeutic regeneration of the colonic mucosa. Thus, identification of differences in mice response to DSS could provide the basis for investigations of susceptibility or resistance to colitis. DSS-induced colitis model study contributes to the understanding of IBD and in the finding for new therapies targeting the reduction of inflammation.
Assuntos
Animais , Masculino , Camundongos , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana/efeitos adversosRESUMO
Background: Colitis murine models have become essential tools to investigate the molecular and cellular mechanisms that lead to inflammatory bowel disease (IBD), such as ulcerative colitis (UC). DSS-induced colitis model faithfully reproduces many of the clinical presentation and immunological disturbances observed in UC. Notwithstanding mice can show differential susceptibilities and responsiveness to dextran sodium sulfate (DSS), and varying DSS concentration and molecular weights appear to be associated with the severity of inflammation. The aim of this study was to analyze the features of mice induced colitis using different DSS concentrations and molecular weights. Materials, Methods and Results: C57BL/6 mice received 2% of high molecular weight DSS (36 000 - 50 000) in drinking water (HDSS2%) or 5% of the same molecular weight (HDSS5%); other group received 5% of low molecular weight DSS (10 000) (LDSS5%). During the 7 days of DSS administration, animals were observed for weight loss, stool consistency and presence of blood feces to determine the disease activity index (DAI). On day 8, colons were removed, measured and weighed for indirect assessment of inflammation. The tissue samples were processed for histological analysis and blood samples were collected for hematological analysis. Our results demonstrated that HDSS5% group began to show significant clinical signs sta
Background: Colitis murine models have become essential tools to investigate the molecular and cellular mechanisms that lead to inflammatory bowel disease (IBD), such as ulcerative colitis (UC). DSS-induced colitis model faithfully reproduces many of the clinical presentation and immunological disturbances observed in UC. Notwithstanding mice can show differential susceptibilities and responsiveness to dextran sodium sulfate (DSS), and varying DSS concentration and molecular weights appear to be associated with the severity of inflammation. The aim of this study was to analyze the features of mice induced colitis using different DSS concentrations and molecular weights. Materials, Methods and Results: C57BL/6 mice received 2% of high molecular weight DSS (36 000 - 50 000) in drinking water (HDSS2%) or 5% of the same molecular weight (HDSS5%); other group received 5% of low molecular weight DSS (10 000) (LDSS5%). During the 7 days of DSS administration, animals were observed for weight loss, stool consistency and presence of blood feces to determine the disease activity index (DAI). On day 8, colons were removed, measured and weighed for indirect assessment of inflammation. The tissue samples were processed for histological analysis and blood samples were collected for hematological analysis. Our results demonstrated that HDSS5% group began to show significant clinical signs sta