Therapeutic applications of bone marrow-derived stem cells in liver transplantation for end-stage liver diseases

2007 ◽  
Vol 52 (18) ◽  
pp. 2449-2456
Author(s):  
HaiYing Luo ◽  
YunFang Wang ◽  
Wei Kong ◽  
XueTao Pei
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Liver Diseases ◽  
Therapeutic Applications ◽  
End Stage

scholarly journals Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4336 ◽  
Author(s):  
Xufeng Fu ◽  
Bin Jiang ◽  
Bingrong Zheng ◽  
Yaping Yan ◽  
Junfeng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Liver Diseases ◽  
Pathological Examination ◽  
Paracrine Effects ◽  
End Stage

Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP). The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells) were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the paracrine effects of MSCs may play an important role in the improvement of liver fibrosis.

scholarly journals Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 386 ◽  
Author(s):  
Viviana Cernigliaro ◽  
Rossella Peluso ◽  
Beatrice Zedda ◽  
Lorenzo Silengo ◽  
Emanuela Tolosano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Transplantation ◽  
Extracellular Vesicles ◽  
Liver Diseases ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Hepatic Function ◽  
Bioactive Molecules ◽  
Cell Based Therapy ◽  
End Stage

Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism requiring a re-transplantation remain major obstacles. Hence, much hope has turned towards cell-based therapy. Hepatocyte-like cells obtained from embryonic stem cells or adult stem cells bearing multipotent or pluripotent characteristics, as well as cell-based systems, such as organoids, bio-artificial liver devices, bioscaffolds and organ printing are indeed promising. New approaches based on extracellular vesicles are also being investigated as cell substitutes. Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. This review provides an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases.

Clinical Labeling and Imaging of Transplanted CD133+/CD34+ Stem Cells in Patients with Ischemic Heart Disease

2012 ◽  
Vol 15 (2) ◽  
pp. 116 ◽  
Author(s):  
Ali Ghodsizad ◽  
Viktor Bordel ◽  
Brian Bruckner ◽  
Mathias Loebe ◽  
Gunter Fuerst ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Separation ◽  
Coronary Artery Bypass Surgery ◽  
Iliac Crest ◽  
Artery Bypass ◽  
Good Manufacturing Practice ◽  
Novel Method ◽  
End Stage Heart Failure ◽  
End Stage

The application of somatic stem cells has been shown to support the recovery of the myocardium in end-stage heart failure. A novel method for the intraoperative isolation and labeling of bone marrow-derived stem cells was established. After induction of general anesthesia, up to 400 mL of bone marrow were harvested from the posterior iliac crest and processed in the operating room under good manufacturing practice conditions by means of the automated cell-selection device Clini-MACS (Miltenyi Biotec). We subsequently injected autologous CD133<sup>+</sup> and CD34<sup>+</sup> stem cells in a predefined pattern around the laser channels in patients undergoing coronary artery bypass surgery and transmyocardial laser procedures. Intraoperative isolation and labeling is an effective cell-separation tool for the future, considering that novel cell markers can be promising new candidates for cell therapy.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
N. Pilat ◽  
L. Unger ◽  
G. A. Berlakovich
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Liver Regeneration ◽  
Orthotopic Liver Transplantation ◽  
Liver Tissue ◽  
Hepatic Regeneration ◽  
Liver Growth ◽  
Cell Source ◽  
The Impact

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.

scholarly journals Stem Cell-Related Studies and Stem Cell-Based Therapies in Liver Diseases

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1116-1122 ◽  
Author(s):  
Wei Zhou ◽  
Erek D. Nelson ◽  
Anan A. Abu Rmilah ◽  
Bruce P. Amiot ◽  
Scott L. Nyberg
Keyword(s):  
Liver Transplantation ◽  
Stem Cell ◽  
Liver Disease ◽  
Liver Failure ◽  
Effective Treatment ◽  
Liver Diseases ◽  
Immunosuppressive Agents ◽  
End Stage Liver Disease ◽  
Effective Interventions ◽  
End Stage

Owing to the increasing worldwide burden of liver diseases, the crucial need for safe and effective interventions for treating end-stage liver failure has been a very productive line of inquiry in the discipline of hepatology for many years. Liver transplantation is recognized as the most effective treatment for end-stage liver disease; however, the shortage of donor organs, high medical costs, and lifelong use of immunosuppressive agents represent major drawbacks and demand exploration for alternative treatments. Stem cell-based therapies have been widely studied in the field of liver diseases and are considered to be among the most promising therapies. Herein, we review recent advances in the application of stem cell-related therapies in liver disease with the aim of providing readers with relevant knowledge in this field and inspiration to spur further inquiry.

Uncommon gastrointestinal complications after liver transplantation: Radiologic findings and clinical features

2013 ◽  
Vol 54 (1) ◽  
pp. 1-7
Author(s):  
Heon-Ju Kwon ◽  
Kyoung Won Kim ◽  
Gi-Won Song ◽  
Shin Hwang ◽  
Hyun Kwon Ha ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Early Detection ◽  
Clinical Features ◽  
Early Treatment ◽  
Liver Diseases ◽  
Gastrointestinal Complications ◽  
Radiologic Findings ◽  
End Stage ◽  
Radiologic Features

There are various uncommon gastrointestinal complications, as liver transplantation becomes increasingly popular as the only curative method for patients with end-stage liver diseases. It is important for radiologists evaluating postoperative liver transplantation recipients to have a perspective on the possible gastrointestinal complications after liver transplantation and their radiologic features for early detection and early treatment. This article illustrates radiologic findings and clinical features of various uncommon gastrointestinal complications after liver transplantation.

scholarly journals Amnion-Derived Mesenchymal Stromal/Stem Cell Paracrine Signals Potentiate Human Liver Organoid Differentiation: Translational Implications for Liver Regeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Antonio Lo Nigro ◽  
Alessia Gallo ◽  
Matteo Bulati ◽  
Giampiero Vitale ◽  
Diego Sebastian Paini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Liver Regeneration ◽  
Conditioned Medium ◽  
Liver Diseases ◽  
Human Liver ◽  
Progenitor Cell ◽  
Liver Repair ◽  
Liver Organoids ◽  
End Stage

The prevalence of end-stage liver diseases has reached very high levels globally. The election treatment for affected patients is orthotopic liver transplantation, which is a very complex procedure, and due to the limited number of suitable organ donors, considerable research is being done on alternative therapeutic options. For instance, the use of cell therapy, such as the transplantation of hepatocytes to promote liver repair/regeneration, has been explored, but standardized protocols to produce suitable human hepatocytes are still limited. On the other hand, liver progenitor and multipotent stem cells offer potential cell sources that could be used clinically. Different studies have reported regarding the therapeutic effects of transplanted mesenchymal stromal/stem cells (MSCs) on end-stage liver diseases. Moreover, it has been shown that delivery of MSC-derived conditioned medium (MSC-CM) can reduce cell death and enhance liver proliferation in fulminant hepatic failure. Therefore, it is believed that MSC-CM contains many factors that probably support liver regeneration. In our work, we used an in vitro model of human liver organoids to study if the paracrine components secreted by human amnion-derived MSCs (hAMSCs) affected liver stem/progenitor cell differentiation. In particular, we differentiated liver organoids derived from bipotent EpCAM+ human liver cells and tested the effects of hAMSC secretome, derived from both two-dimensional (2D) and three-dimensional (3D) hAMSC cultures, on that model. Our analysis showed that conditioned medium (CM) produced by 3D hAMSCs was able to induce an over-expression of mature hepatocyte markers, such as ALB, NTCP, and CYP3A4, compared with both 2D hAMSC cultures and the conventional differentiation medium (DM). These data were confirmed by the over-production of ALB protein and over-activity of CYP3A4 observed in organoids grown in 3D hAMSC-CM. Liver repair dysfunction plays a role in the development of liver diseases, and effective repair likely requires the normal functioning of liver stem/progenitor cells. Herein, we showed that hAMSC-CM produced mainly by 3D cultures had the potential to increase hepatic stem/progenitor cell differentiation, demonstrating that soluble factors secreted by those cells are potentially responsible for the reaction. This work shows a potential approach to improve liver repair/regeneration also in a transplantation setting.

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