Hematopoietic stem cell trafficking in liver injury

Dalakas, Evangelos; Newsome, Philip N.; Harrison, David J.; Plevris, John

doi:10.1096/fj.04-2604rev

Cited by 102 publications

(78 citation statements)

References 103 publications

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“…Thus, discrepancies in detecting both Thy1 and AFP in hepatic progenitors may arise from differences in the type of treatment as well as time of phenotypic analysis. Corroborating previous studies, we propose that, during liver injury, two different cell types may be involved in repopulating the regenerating organ: (1) c-kit + (and likely Thy1 + ) HSCs which are mobilized from the BM and invade the liver through the circulation [39] and (2) endogenous OV6/CK19/Rab3b + oval cells which emanate from biliary ducts [12,32].…”

Section: Discussionsupporting

confidence: 79%

“…Human studies have shown increased levels of circulating HSCs in response to liver trauma [37,38]. These cells are thought to be activated in the BM and mobilized from the circulation in order to repopulate the damaged tissue [39]. We thus investigated whether HSCs expressing c-kit and potentially Thy1 could be detected in the BM of 2-AAF/CCl 4 -treated rats.…”

Section: Immunohistochemical Characteristics Of Activated Hepatic Promentioning

confidence: 99%

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Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

Corcelle¹,

Stieger

Gjinovci³

et al. 2006

Experimental Cell Research

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Despite extensive studies, the hematopoietic versus hepatic origin of liver progenitor oval cells remains controversial. The aim of this study was to determine the origin of such cells after liver injury and to establish an oval cell line. Rat liver injury was induced by subcutaneous insertion of 2-AAF pellets for 7 days with subsequent injection of CCl 4 . Livers were removed 9 to 13 days post-CCl 4 treatment. Immunohistochemistry was performed using anti-c-kit, OV6, Thy1, CK19, AFP, vWF and Rab3b. Isolated non-parenchymal cells were grown on mouse embryonic fibroblast, and their gene expression profile was characterized by RT-PCR. We identified a subpopulation of OV6/CK19/Rab3b-expressing cells that was activated in the periportal region of traumatized livers. We also characterized a second subpopulation that expressed the HSCs marker c-kit but not Thy1. Although we successfully isolated both cell types, OV6/CK19/Rab3b + cells fail to propagate while c-kit + -HSCs appeared to proliferate for up to 7 weeks. Cells formed clusters which expressed c-kit, Thy1 and albumin. Our results indicate that a bona fide oval progenitor cell population resides within the liver and is distinct from c-kit + -HSCs. Oval cells require the hepatic niche to proliferate, while cells mobilized from the circulation proliferate and transdifferentiate into hepatocytes without evidence of cell fusion.

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Section: Discussionsupporting

confidence: 79%

Section: Immunohistochemical Characteristics Of Activated Hepatic Promentioning

confidence: 99%

Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

Corcelle¹,

Stieger

Gjinovci³

et al. 2006

Experimental Cell Research

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“…A direct interaction between MMP9 and IL-8 has been reported in hematopoietic stem cell trafficking in liver injury (17,20), in retinoic acid syndrome (45), and in leucocytes (51). Beklen et al (7) showed that there was an upregulation of both MMP9 and IL-8 in periodontitis.…”

Section: Discussionmentioning

confidence: 99%

Constitutive expression of MMP9 in intestinal epithelium worsens murine acute colitis and is associated with increased levels of proinflammatory cytokine Kc

Liu

Patel

Walter

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Liu H, Patel NR, Walter L, Ingersoll S, Sitaraman SV, Garg P. Constitutive expression of MMP9 in intestinal epithelium worsens murine acute colitis and is associated with increased levels of proinflammatory cytokine Kc. Am J Physiol Gastrointest Liver Physiol 304: G793-G803, 2013. First published March 7, 2013 doi:10.1152/ajpgi.00249.2012.-Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic inflammatory disease associated with an increased risk for colon cancer. Matrix metalloproteinases (MMPs) are the predominant proteinases expressed in the gut mucosa during active IBD. Our laboratory has previously demonstrated that epithelial-derived MMP9 is absent in normal colonic tissue but is upregulated during IBD. In this study MMP9 transgenic mice (Tg-villin-MMP9) are generated specifically to overexpress MMP9 in intestinal epithelium to examine the role and underlying mechanism by which it modulates the pathogenesis of acute colitis. Dextran sodium sulfate (3% DSS)-and Salmonella typhimurium (S.T.)-induced colitis models were used to study gut inflammation in Tg-villin-MMP9 and wild-type littermates (WT). Colonic tissue was analyzed via Western blot, histology, myeloperoxidase (MPO) assay, and quantitative PCR. Tg-villin-MMP9 mice expressed significantly increased MMP9 mRNA and protein expression at basal level. There was a significant decrease in the goblet cells, but a significant increase in proliferation and apoptosis were observed among Tg-villin-MMP9 mice compared with WT mice. There was also a significant increase in the proinflammatory chemokine Kc among Tg-villin-MMP9 compared with WT mice. Tg-villin-MMP9 exhibited a severe inflammatory response than WT mice in both DSSand S.T.-induced colitis models as evident by greater weight loss and higher clinical score, histological score, and MPO activity, which correlated with relative levels of Kc mRNA. MMP9 expressed by intestinal epithelial cells mediates inflammation in colitis with simultaneous increase in proinflammatory cytokine Kc. inflammation; dextran sodium sulfate; transgenic mice; IL-8 INFLAMMATORY BOWEL DISEASE (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disease that affects the entire gastrointestinal (GI) tract and the colonic mucosa and is associated with an increased risk for colon cancer. IBD is characterized by relapses (acute flare) and remissions, which are related to genetic basis and involve immune-mediated tissue injury followed by repair. Recent studies have shown that cytokines play a key role in regulating IBD (9, 40). There is increased incidence of IBD in urban areas of industrialized nations (29,42). Matrix metalloproteinases (MMPs) are a group of zinc-dependent enzymes with proteolytic activity against extracellular matrix (ECM) proteins and are also known to play an important role for normal tissue remodeling (47). MMPs have also been shown to be involved in several pathological conditions such as IBD, tumor invasion, and colorect...

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“…Several lines of evidence have shown that mammalian adult stem cells display ''plasticity,'' the ability to transdifferentiate into other tissue types (15)(16)(17)(18), although the mechanism remains controversial (19). It was hypothesized that stem cell plasticity may result from a cell fusion mechanism (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Multiorgan engraftment and differentiation of human cord blood CD34 ⁺ Lin ⁻ cells in goats assessed by gene expression profiling

Zeng

Chen

Baldwin

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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To investigate multitissue engraftment of human primitive hematopoietic cells and their differentiation in goats, human CD34 ؉ Lin ؊ cord blood cells transduced with a GFP vector were transplanted into fetal goats at 45-55 days of gestation. GFP ؉ cells were detected in hematopoietic and nonhematopoietic organs including blood, bone marrow, spleen, liver, kidney, muscle, lung, and heart of the recipient goats (1.2-36% of all cells examined). We identified human ␤2 microglobulin-positive cells in multiple tissues. GFP ؉ cells sorted from the perfused liver of a transplant goat showed human insulin-like growth factor 1 gene sequences, indicating that the engrafted GFP ؉ cells were of human origin. A substantial fraction of cells engrafted in goat livers expressed the human hepatocyte-specific antigen, proliferating cell nuclear antigen, albumin, hepatocyte nuclear factor, and GFP. DNA content analysis showed no evidence for cellular fusion. Long-term engraftment of GFP ؉ cells could be detected in the blood of goats for up to 2 yr. Microarray analysis indicated that human genes from a variety of functional categories were expressed in chimeric livers and blood. The human͞goat xenotransplant model provides a unique system to study the kinetics of hematopoietic stem cell engraftment, gene expression, and possible stem cell plasticity under noninjured conditions. hematopoietic stem cell ͉ transplantation ͉ plasticity ͉ microarray

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Hematopoietic stem cell trafficking in liver injury

Cited by 102 publications

References 103 publications

Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

Constitutive expression of MMP9 in intestinal epithelium worsens murine acute colitis and is associated with increased levels of proinflammatory cytokine Kc

Multiorgan engraftment and differentiation of human cord blood CD34 ⁺ Lin ⁻ cells in goats assessed by gene expression profiling

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Hematopoietic stem cell trafficking in liver injury

Cited by 102 publications

References 103 publications

Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

Constitutive expression of MMP9 in intestinal epithelium worsens murine acute colitis and is associated with increased levels of proinflammatory cytokine Kc

Multiorgan engraftment and differentiation of human cord blood CD34 + Lin − cells in goats assessed by gene expression profiling

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Multiorgan engraftment and differentiation of human cord blood CD34 ⁺ Lin ⁻ cells in goats assessed by gene expression profiling