Oliveira SA, Souza BSF, Guimarães-Ferreira CA, Barreto ES, Souza SC, Freitas LAR, Ribeiro-dos-Santos R, Soares MBP. Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni. World J Gastroenterol 2008; 14(38): 5842-5850 [PMID: 18855983 DOI: 10.3748/wjg.14.5842]
Corresponding Author of This Article
Milena Botelho Pereira Soares, PhD, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Brotas, Salvador 40295-001, BA, Brazil. milena@bahia.fiocruz.br
Article-Type of This Article
Basic Research
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World J Gastroenterol. Oct 14, 2008; 14(38): 5842-5850 Published online Oct 14, 2008. doi: 10.3748/wjg.14.5842
Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni
Sheilla Andrade Oliveira, Bruno Solano Freitas Souza, Carla Adriana Guimarães-Ferreira, Elton Sá Barreto, Siane Campos Souza, Luiz Antonio Rodrigues Freitas, Ricardo Ribeiro-dos-Santos, Milena Botelho Pereira Soares
Sheilla Andrade Oliveira, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Brotas, 40295-001 Salvador, BA, Brazil and Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Av Moraes Rego s/n, Cidade Universitária, Recife 50670-420, PE, Brazil
Bruno Solano Freitas Souza, Carla Adriana Guimarães-Ferreira, Elton Sá Barreto, Siane Campos Souza, Luiz Antonio Rodrigues Freitas, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Brotas, Salvador 40295-001, BA, Brazil
Ricardo Ribeiro-dos-Santos, Milena Botelho Pereira Soares, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Brotas, 40295-001 Salvador, BA, Brazil and Hospital São Rafael, Av São Rafael, 2152, São Marcos, Salvador 41256-900, BA, Brazil
Author contributions: Oliveira SA designed, conducted the study and analyzed the data; Souza BSF and Barreto ES conducted the morphometric and immunofluorescence studies; Guimarães-Ferreira CA and Souza SC performed FISH and PCR analyses; Freitas LAR performed the histopathological analyses; Ribeiro-dos-Santos R and Soares MBP were involved in designing the study, reviewing and interpreting the results. All authors were involved in drafting the manuscript.
Supported by Instituto do Milênio de Bioengenharia Tecidual (IMBT, CNPq/MCT), Rede Nordeste de Biotecnologia (RENORBIO, FINEP/MCT), Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) and Fundação Oswaldo Cruz (FIOCRUZ)
Correspondence to: Milena Botelho Pereira Soares, PhD, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Brotas, Salvador 40295-001, BA, Brazil. milena@bahia.fiocruz.br
Telephone: +55-71-31762260 Fax: +55-71-31762292
Received: July 8, 2008 Revised: August 21, 2008 Accepted: August 28, 2008 Published online: October 14, 2008
Abstract
AIM: To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.
METHODS: Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-β), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.
RESULTS: Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.mansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.
CONCLUSION: In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.
