scholarly journals Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy

2017 ◽  
Vol 26 (2) ◽  
pp. 351-364 ◽  
Author(s):  
Astrid Herrero ◽  
Julie Prigent ◽  
Catherine Lombard ◽  
Valérie Rosseels ◽  
Martine Daujat-Chavanieu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cell Therapy ◽  
Liver Regeneration ◽  
Progenitor Cells ◽  
Human Liver ◽  
Liver Weight ◽  
Vehicle Group ◽  
Hepatic Tissue ◽  
Extended Hepatectomy ◽  
Extensive Hepatectomy

There is growing evidence that cell therapy constitutes a promising strategy for liver regenerative medicine. In the setting of hepatic cancer treatments, cell therapy could prove a useful therapeutic approach for managing the acute liver failure that occurs following extended hepatectomy. In this study, we examined the influence of delivering adult-derived human liver stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model ( Rag2−/-IL2Rg -/-) that had undergone a 70% hepatectomy procedure. The hepatic mesenchymal cells were intrasplenically infused either immediately after surgery ( n = 26) or following a critical 3-day period ( n = 26). We evaluated the cells' capacity to engraft at day 1 and day 7 following transplantation by means of human Alu qPCR quantification, along with histological assessment of human albumin and α-smooth muscle actin. In addition, cell proliferation (anti-mouse and human Ki-67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At day 1 posttransplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week posttransplantation this ratio was significantly improved ( p < 0.016) in mice receiving ADHLSC injection at day 3 posthepatectomy (1.7%), compared to those injected at the time of surgery (1%). On the basis of liver weight, mouse liver regeneration was more extensive 1 week posttransplantation in mice transplanted with ADHLSCs (+65.3%) compared to that of mice from the sham vehicle group (+42.7%). In conclusion, infusing ADHLSCs 3 days after extensive hepatectomy improves the cell engraftment and murine hepatic tissue regeneration, thereby confirming that ADHLSCs could be a promising cell source for liver cell therapy and hepatic tissue repair.

scholarly journals The Herbal Compound “Diwu Yanggan” Modulates Liver Regeneration by Affecting the Hepatic Stem Cell Microenvironment in 2-Acetylaminofluorene/Partial Hepatectomy Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Bin-Bin Zhao ◽  
Han-Min Li ◽  
Xiang Gao ◽  
Zhi-Hua Ye ◽  
Si-Si Cheng
Keyword(s):  
Liver Regeneration ◽  
Survival Rates ◽  
Normal Group ◽  
Vehicle Group ◽  
Hepatic Tissue ◽  
Oval Cell ◽  
Double Positive ◽  
Cell Markers ◽  
Suspension Array ◽  
And Function

Ethnopharmacological Relevance.“Diwu Yanggan” (DWYG) has been reported to regulate liver regeneration, modulate the immune response, ameliorate liver injury, kill virus, ameliorate liver fibrosis, and suppress hepatic cancer. However, its mechanisms are still unknown.Objectives.To investigate the effects of DWYG on oval cell proliferation in 2-AAF/PH rats and determine its mechanism.Methods.Wistar rats were randomly distributed into normal group, sham group, vehicle group, and DWYG group. Hepatic pathological changes were examined by H&E staining. The oval cell markers CD34, AFP, CK-19 and hematopoietic cell markers CD45, Thy1.1, and hepatocyte marker ALB were examined with immunohistochemistry. The percentage of CD34/CD45 double-positive cells in bone marrow was detected by flow cytometry. Cytokine levels were measured with the Bio-plex suspension array system.Results. DWYG significantly increased the survival rates of 2-AAF/PH rats and promoted liver regeneration. Furthermore, DWYG increased the ratio of CD34/CD45 double-positive cells on days 10 and 14. In addition, DWYG gradually restored IL-1, GRO/KC, and VEGF levels to those of the normal group.Conclusions.DWYG increases 2-AAF/PH rat survival rates, suppresses hepatic precarcinoma changes, and restores hepatic tissue structure and function. DWYG may act by modulating the hepatic microenvironment to support liver regeneration.

scholarly journals Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1127 ◽  
Author(s):  
Irina V. Kholodenko ◽  
Leonid K. Kurbatov ◽  
Roman V. Kholodenko ◽  
Garik V. Manukyan ◽  
Konstantin N. Yarygin
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Attractive Alternative ◽  
Short Supply

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.

scholarly journals Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Catherine A. Lombard ◽  
Gwenaëlle Sana ◽  
Joël LeMaoult ◽  
Mehdi Najar ◽  
Joachim Ravau ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Progenitor Cells ◽  
Liver Cell ◽  
Human Liver ◽  
Hla Class I ◽  
Liver Cells ◽  
Human Hepatocytes ◽  
Oncostatin M ◽  
Hepatogenic Differentiation

One of the main challenges in liver cell therapy (LCT) is the induction of a tolerogenic microenvironment to promote graft acceptance in the recipient. Little is known about the immunomodulatory potential of the hepatic cells used in liver cell therapy. In this work, we wanted to evaluate the immunosuppressive properties of human hepatocytes and adult-derived human liver stem/progenitor cells (ADHLSCs), as well as the potential involvement of the immunomodulatory molecule HLA-G. We demonstrated that both cell types were capable of inhibiting the proliferative response of PBMCs to an allogenic stimulus and that the immune inhibitory potential of ADHLSCs, although lower than that of hepatocytes, increased after hepatogenic differentiation. We demonstrated that liver cells express HLA-G and that the immune inhibition pattern was clearly associated to its expression. Interestingly, HLA-G expression increased after the third step of differentiation, wherein oncostatin M (OSM) was added. A 48 hr treatment with OSM was sufficient to induce HLA-G expression in ADHLSCs and result in immune inhibition. Surprisingly, blocking HLA-G partially reversed the immune inhibition mediated by hepatocytes and differentiated ADHLSCs, but not that of undifferentiated ADHLSCs, suggesting that additional immune inhibitory mechanisms may be used by these cells. In conclusion, we demonstrated that both hepatocytes and ADHLSCs present immunomodulatory properties mediated, at least in part, through HLA-G, which can be upregulated following hepatogenic differentiation or liver cell pretreatment with OSM. These observations open up new perspectives for the induction of tolerance following LCT and for potential therapeutic applications of these liver cells.

scholarly journals Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy

2013 ◽  
Vol 22 (8) ◽  
pp. 1369-1380 ◽  
Author(s):  
Dung Ngoc Khuu ◽  
Omar Nyabi ◽  
Cédric Maerckx ◽  
Etienne Sokal ◽  
Mustapha Najimi
Keyword(s):  
Liver Regeneration ◽  
Progenitor Cells ◽  
Human Liver ◽  
Mouse Liver ◽  
Adult Human

scholarly journals Methods of Liver Stem Cell Therapy in Rodents as Models of Human Liver Regeneration in Hepatic Failure

2015 ◽  
Vol 5 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Nasser Hashemi Goradel ◽  
Masoud Darabi ◽  
karim Shamsasenjan ◽  
Mostafa Ejtehadifar ◽  
Sarah zahedi
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Liver Regeneration ◽  
Stem Cell Therapy ◽  
Hepatic Failure ◽  
Human Liver

scholarly journals Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
S. Sakinah ◽  
Sivan Padma Priya ◽  
Pooi Ling Mok ◽  
Rusheni Munisvaradass ◽  
Seoh Wei Teh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Model ◽  
Cell Therapy ◽  
Dengue Virus ◽  
Progenitor Cells ◽  
Stem Cell Therapy ◽  
Dengue Infection ◽  
Target Cells ◽  
Hematopoietic Stem

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.

EpCam-specific Gold Nanoparticles for Detection, Live-imaging and Rapid Enrichment of Adult Human Liver Progenitor Cells

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
N Fekete-Drimusz ◽  
J de la Roche ◽  
F Vondran ◽  
CL Sajti ◽  
MP Manns ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Progenitor Cells ◽  
Human Liver ◽  
Live Imaging ◽  
Adult Human

Breakthrough Regenerative Cardiopoietic Stem Cells and Related Technologies in the Field of Cardiovascular Medicine – From Bench to Bedside

2012 ◽  
Vol 7 (1) ◽  
pp. 14
Author(s):  
Christian Homsy ◽  
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Cardiac Disease ◽  
Cardiac Tissue ◽  
Cardiac Repair ◽  
Cardiac Diseases ◽  
Cardiac Progenitor Cells ◽  
Biotechnology Company ◽  
Cardiovascular Medicine

The scale of cardiac diseases, and in particular heart failure and acute myocardial infarction, emphasises the need for radically new approaches, such as cell therapy, to address the underlying cause of the disease, the loss of functional myocardium. Stem cell-based therapies, whether through transplanted cells or directing innate repair, may provide regenerative approaches to cardiac diseases by halting, or even reversing, the events responsible for progression of organ failure. Cardio3 BioSciences, a leading Belgian biotechnology company focused on the discovery and development of regenerative and protective therapies for the treatment of cardiac disease, was founded in this context in 2004. The company is developing a highly innovative cell therapy approach based on a platform designed to reprogramme the patient’s own stem cells into cardiac progenitor cells. The underlying rationale behind this approach is that, in order to reconstruct cardiac tissue, stem cells need to be specific to cardiac tissue. The key is therefore to provide cardiac-specific progenitor cells to the failing heart to induce cardiac repair.

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