Bone marrow progenitor cells do not contribute to liver fibrogenic cells

Paredes, Bruno Diaz; Faccioli, Lanuza Alaby Pinheiro; Quintanilha, Luiz Fernando; Asensi, Karina Dutra; Valle, Camila Zaverucha do; Canary, Paulo César; Takiya, Christina Maeda; Carvalho, Antônio Carlos Campos de; Goldenberg, Regina Coeli dos Santos

doi:10.4254/wjh.v4.i10.274

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…In the present study, we detected and analysed GFP+ BM cells that migrated to the heart after T. cruzi infection in a chimeric mouse model of chagasic cardiomyopathy. Chimeric mice have been used to study the participation of BM cells in the regeneration of different tissues, such as skeletal muscle, the liver, and the heart ( Epperly et al 2003 , Fazel et al 2006 , Abedi et al 2007 , Paredes et al 2012 , Souza et al 2014 ). To develop this model, we followed the protocol used by Paredes et al (2012) , which had already been established in our laboratory, with some modifications.…”

Section: Discussionmentioning

confidence: 99%

“…Generation of chimeric mice - To generate chimeric mice, 34 C57Bl/6 mice (weighing approximately 25 g) were exposed to whole body radiation (7 Gy) in a linear accelerator (VarianClinac 2100 CD) used for radiotherapy, resulting in BM ablation as previously described ( Paredes et al 2012 ). BM cells were harvested from the femurs and tibiae of GFP transgenic mice at two months of age by centrifugation (1500 × g for 3 min).…”

Section: Methodsmentioning

confidence: 99%

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Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

Irion

Paredes

Brasil

et al. 2017

Mem. Inst. Oswaldo Cruz

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BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare.OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice.METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice.FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups.MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

Irion

Paredes

Brasil

et al. 2017

Mem. Inst. Oswaldo Cruz

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“…BALB/c, C57BL/6, and enhanced green fluorescent protein (EGFP)-expressing C57BL/6-Tg(CAG-EGFP) mice (Paredes et al, 2012) were used in this study. Animals were housed in standard conditions in a temperature-controlled room on a 12:12 h light/dark cycle.…”

Section: Animalsmentioning

confidence: 99%

Long‐term recruitment of peripheral immune cells to brain scars after a neonatal insult

Bolini,

Campos,

Spiess

et al. 2023

Glia

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Although brain scars in adults have been extensively studied, there is less data available regarding scar formation during the neonatal period, and the involvement of peripheral immune cells in this process remains unexplored in neonates. Using a murine model of neonatal hypoxic–ischemic encephalopathy (HIE) and confocal microscopy, we characterized the scarring process and examined the recruitment of peripheral immune cells to cortical and hippocampal scars for up to 1 year post‐insult. Regional differences in scar formation were observed, including the presence of reticular fibrotic networks in the cortex and perivascular fibrosis in the hippocampus. We identified chemokines with chronically elevated levels in both regions and demonstrated, through a parabiosis‐based strategy, the recruitment of lymphocytes, neutrophils, and monocyte‐derived macrophages to the scars several weeks after the neonatal insult. After 1 year, however, neutrophils and lymphocytes were absent from the scars. Our data indicate that peripheral immune cells are transient components of HIE‐induced brain scars, opening up new possibilities for late therapeutic interventions.

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“…The accumulation of collagen interferes with hepatic architecture and function which may subsequently progress into cirrhosis and liver failure [48]. BM derived cells have been proposed to contribute to collagen production and fibrosis in different models [49–51]; however, their contribution to scar tissue formation in the liver remains controversial [52–54]. …”

Section: Bm Derived Stem Cells and Fibrosismentioning

confidence: 99%

Implication for Bone Marrow Derived Stem Cells in Hepatocyte Regeneration after Orthotopic Liver Transplantation

Pilat

Unger

Berlakovich

2013

International Journal of Hepatology

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The liver has the outstanding ability to regenerate itself and restore parenchymal tissue after injury. The most common cell source in liver growth/regeneration is replication of preexisting hepatocytes although liver progenitor cells have been postulated to participate in liver regeneration in cases of massive injury. Bone marrow derived hematopoietic stem cells (BM-HSC) have the formal capacity to act as a source for hepatic regeneration under special circumstances; however, the impact of this process in liver tissue maintenance and regeneration remains controversial. Whether BM-HSC are involved in liver regeneration or not would be of particular interest as the cells have been suggested to be an alternative donor source for the treatment of liver failure. Data from murine models of liver disease show that BM-HSC can repopulate liver tissue and restore liver function; however, data obtained from human liver transplantation show only little evidence for liver regeneration by this mechanism. The cell source for liver regeneration seems to depend on the nature of regeneration process and the extent of injury; however, the precise mechanisms still need to be resolved. Current data suggest, that in human orthotopic liver transplantation, liver regeneration by BM-HSC is a rather rare event and therefore not of clinical relevance.

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Bone marrow progenitor cells do not contribute to liver fibrogenic cells

Abstract: BM progenitor cells do not contribute to fibrosis, but there is a high recruitment of inflammatory cells that stimulates HSCs and MFs of liver origin.

Cited by 7 publications

References 36 publications

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

Long‐term recruitment of peripheral immune cells to brain scars after a neonatal insult

Implication for Bone Marrow Derived Stem Cells in Hepatocyte Regeneration after Orthotopic Liver Transplantation

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