Bone marrow cells play only a very minor role in chronic liver regeneration induced by a choline-deficient, ethionine-supplemented diet

Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model.Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors.Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group.Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

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Prevention of Liver Fibrosis by Intrasplenic Injection of High-Density Cultured Bone Marrow Cells in a Rat Chronic Liver Injury Model

PLoS ONE ◽

10.1371/journal.pone.0103603 ◽

2014 ◽

Vol 9 (9) ◽

pp. e103603 ◽

Cited By ~ 9

Author(s):

Jie Lian ◽

Yang Lu ◽

Peng Xu ◽

Ai Ai ◽

Guangdong Zhou ◽

...

Keyword(s):

Bone Marrow ◽

Liver Fibrosis ◽

Liver Injury ◽

Bone Marrow Cells ◽

High Density ◽

Chronic Liver ◽

Chronic Liver Injury ◽

Injury Model ◽

Intrasplenic Injection ◽

Marrow Cells

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Bone Marrow Cells Enhance Liver Regeneration After Massive Hepatectomy in Mice

Digestive Diseases and Sciences ◽

10.1007/s10620-014-3032-7 ◽

2014 ◽

Vol 59 (7) ◽

pp. 1484-1489 ◽

Cited By ~ 6

Author(s):

Masaki Kaibori ◽

Yasushi Adachi ◽

Tomohiko Shimo ◽

Morihiko Ishizaki ◽

Kosuke Matsui ◽

...

Keyword(s):

Bone Marrow ◽

Liver Regeneration ◽

Bone Marrow Cells ◽

Massive Hepatectomy ◽

Marrow Cells

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Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration

Cell Reports ◽

10.1016/j.celrep.2016.12.008 ◽

2017 ◽

Vol 18 (1) ◽

pp. 107-121 ◽

Cited By ~ 20

Author(s):

Elisa Pedone ◽

Vlad-Aris Olteanu ◽

Lucia Marucci ◽

Maria Isabel Muñoz-Martin ◽

Sameh A. Youssef ◽

...

Keyword(s):

Bone Marrow ◽

Liver Regeneration ◽

Mouse Liver ◽

Bone Marrow Cells ◽

Dynamics And Function ◽

And Function ◽

Marrow Cells

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Fructus polygoni orentalis extract inhibited liver regeneration and proliferation of bone marrow cells of rat after partial hepatectomy

Genetics and Molecular Research ◽

10.4238/2015.july.13.12 ◽

2015 ◽

Vol 14 (3) ◽

pp. 7671-7679 ◽

Cited By ~ 2

Author(s):

J.Y. Yang ◽

J.S. Wang ◽

H.B. Liu

Keyword(s):

Bone Marrow ◽

Liver Regeneration ◽

Partial Hepatectomy ◽

Bone Marrow Cells ◽

Marrow Cells

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Intrahepatic Portal Application of Autologous CD133+ Bone Marrow Stem Cells to the Liver - Early Experience with a Novel Concept To Support Hepatic Regeneration.

Blood ◽

10.1182/blood.v104.11.2338.2338 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2338-2338

Author(s):

Jan Schulte am Esch ◽

Wolfram T. Knoefel ◽

Michael Klein ◽

Alireza Ghodsizad ◽

Guenter Fuerst ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Liver Resection ◽

Liver Regeneration ◽

Bone Marrow Cells ◽

Bone Marrow Stem Cells ◽

Stem Cell Marker ◽

Liver Mass ◽

Novel Concept ◽

Marrow Cells

Abstract The liver has a large capacity for regeneration after surgical resection. However, below a critical level of future liver remnant volume, liver resection is accompanied by significant increase of postoperative liver failure and mortality. There is accumulating evidence for the contribution of hematopoetic stem cells to participate in liver regeneration. Here we report on three patients that were subjected to intra portal application of CD133+ bone marrow stem cells to support a standard concept of preoperative proliferation of the prospective liver mass. In all three cases, scheduled for right hepatic trisegmentectomy, isolated portal venous embolisation (PVE) of liver segments I and IV–VIII routinely utilized to expand left lateral hepatic segments II/III (prospective remaining liver mass) was questionably sufficient. Autologous bone marrow cells were enriched for stem cell marker CD133 utilizing an immunomagnetic device. For characterisation, each preparation of Cells was subjected to FACS-analyses for markers CD34, CD45 and CD133. Absolute numbers of 2.4 to 12.3 mio CD133+ cells were porto-venously applied to the left-lateral liver segments following PVE of contra lateral liver segments. The treatment with CD133+ was well tolerated without obvious side effects. CT-scan volumetry revealed 2.5 fold increased mean proliferation rates of left-lateral segments when compared to a group of three consecutive patients, treated with the same therapeutic concept - except the application of stem cells. Two to three weeks after intervention, future remnant liver volume was sufficient to perform expanded liver resection, which was applied safely to all patients. This first experience with a novel concept of portovenous application of CD133+ bone marrow cells subsequent to porto-venous embolisation encourages to carry out future controlled trials to evaluate the effectiveness of this approach to boost liver regeneration processes.

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