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Bone Marrow Mononuclear Cell Transplantation Improves Survival and Induces Hepatocyte Proliferation in Rats after CCl4 Acute Liver Damage

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Abstract

Aim

The aim of this research was to evaluate the effects of bone marrow mononuclear cell (BMC) transplantation in rats with toxic acute liver damage induced by carbon tetrachloride (CCl4).

Methods

Cells from male Wistar rats were obtained using Ficoll density gradient and 0.2 ml (1 × 106 cells) were injected into the portal vein of female rats (n = 15) 24 h after damage. Sham group (n = 15) was performed injecting only vehicle in CCl4-treated animals. Survival, liver histology, number of mitosis and apoptosis, and identification of stained donor cells were observed 72 h after damage. ALT levels were measured at 0 h, 24 h, 48 h, and 72 h after injury.

Results

Donor cells could be detected in recipient rats’ livers by fluorescence staining and Sry PCR. The treated group revealed a significant improvement in survival rate after 72 h (p = 0.003). There was also a significant increase in the number of mitotic events in treated livers (p = 0.029). This result was confirmed using an in vitro cell proliferation assay in isolated hepatocytes treated with conditioned medium from BMC. ALT was reduced in the treated group after 72 h (p = 0.034).

Conclusions

Results indicate that BMC transplantation has potential as a new therapeutic option for acute liver disease and suggest that these cells may contribute to hepatic recovery through release of mitotic cytokines.

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Acknowledgments

We would like to thank Simone Castro (Pharmacy School, UFRGS) for her support and comments and Katia Delgado do Santos (Hematology Unit, HCPA) for technical assistance. We also thank Daniela Rodrigues (Post-Graduation Program in Medical Sciences: Gastroenterology, UFRGS) for helping us with hepatocyte isolation. This work was supported by CNPq, Millennium Institutes- Gene Therapy Network and FIPE-HCPA. Roberto Giugliani and Ursula Matte are recipients of CNPq research scholarships. Guilherme Baldo is a recipient of a CAPES scholarship.

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Authors and Affiliations

  1. Gene Therapy Center, Research Center, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil

    Guilherme Baldo, Roberto Giugliani, Carolina Uribe, Maria Cristina Belardinelli & Ursula Matte

  2. Post-Graduation Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Guilherme Baldo, Roberto Giugliani & Maria Cristina Belardinelli

  3. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Roberto Giugliani

  4. Experimental Animal Unit-Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Marcos Eugênio Soares Duarte

  5. Pathology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Luíse Meurer

  6. Experimental Hepatology Laboratory, Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Themis Reverbel da Silveira & Ursula Matte

Authors
  1. Guilherme Baldo
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  2. Roberto Giugliani
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  3. Carolina Uribe
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  4. Maria Cristina Belardinelli
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  5. Marcos Eugênio Soares Duarte
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  6. Luíse Meurer
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  7. Themis Reverbel da Silveira
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  8. Ursula Matte
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Corresponding author

Correspondence to Ursula Matte.

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Baldo, G., Giugliani, R., Uribe, C. et al. Bone Marrow Mononuclear Cell Transplantation Improves Survival and Induces Hepatocyte Proliferation in Rats after CCl4 Acute Liver Damage. Dig Dis Sci 55, 3384–3392 (2010). https://doi.org/10.1007/s10620-010-1195-4

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  • DOI: https://doi.org/10.1007/s10620-010-1195-4

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