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mesenchymal stem cells in liver disease

Lucas-Sebastian Spitzhorn, Claus Kordes, Matthias Megges, Iris Sawitza, Silke Götze, Doreen Reichert, Peggy Schulze-Matz, Nina Graffmann, Martina Bohndorf, Wasco Wruck, Jan Philipp Köhler, Diran Herebian, Ertan Mayatepek, Richard O Oreffo, Dieter Häussinger, James Adjaye
Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1A1 (Ugt1a1) gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In the present study, the Gunn rat was used as an animal model for heritable liver dysfunction. Human mesenchymal stem cells (iMSC) derived from embryonic stem cells (H1) and induced pluripotent stem cells were transplanted into Gunn rats after partial hepatectomy. The iMSCs engrafted and survived in the liver for up to 2 months. The transplanted iMSCs differentiated into functional hepatocytes as evidenced by partially suppressed hyperbilirubinemia and expression of multiple human-specific hepatocyte markers such as Albumin, hepatocyte nuclear factor 4α, UGT1A1, Cytokeratin 18, bile salt export pump, multidrug resistance protein 2, Na/taurocholate-cotransporting polypeptide and α-Fetoprotein...
October 3, 2018: Stem Cells and Development
Sonia Emilia Selicean, Ciprian Tomuleasa, Ravnit Grewal, Graca Almeida-Porada, Ioana Berindan-Neagoe
Primary myelofibrosis (PMF) is the most aggressive Philadelphia-negative (Ph-) myeloproliferative neoplasm (MPN), characterized by bone marrow (BM) insufficiency, myelofibrosis (MF), osteosclerosis, neoangiogenesis, and extramedullary hematopoiesis (EMH) in spleen and liver. Presently, there is no curative treatment for this disease and therapy consists primarily of symptom relief and, in selected cases, allogeneic hematopoietic stem cell transplant (alloHSCT). PMF's major defining characteristics, as well as several recently described aspects of its cellular and molecular pathophysiology all support a critical role for dysregulated cell-cell/cell-extracellular matrix interactions and cytokine/chemokine signaling within the BM niche in the natural history of this disease...
October 2, 2018: Leukemia & Lymphoma
Hongling Li, Li Zhu, Huimin Chen, Tangping Li, Qin Han, Shihua Wang, Xinglei Yao, Hongli Feng, Linyuan Fan, Shaorong Gao, Richard Boyd, Xu Cao, Ping Zhu, Jing Li, Armand Keating, Xiaodong Su, Robert Chunhua Zhao
Cell transplantation holds considerable promise for end-stage liver diseases but identifying a suitable, transplantable cell type has been problematic. Here, we describe a novel type of mesenchymal stem cells (MSCs) from human adipose tissue. These cells are different from previously reported MSCs, they are in the euchromatin state with epigenetic multipotency, and express pluripotent markers MYC, KLF4, and GMNN. Most of the genes associated with germ layer specification are modified by H3K4me3 or co-modified by H3K4me3 and H3K27me3...
September 11, 2018: Stem Cells Translational Medicine
Yang Liu, Haozhen Ren, Jinglin Wang, Faji Yang, Jun Li, Yuan Zhou, Xianwen Yuan, Wei Zhu, Xiaolei Shi
Bone marrow-derived mesenchymal stem cells (MSCs) have been recently used in clinical trials as treatment for liver diseases. However, the underlying mechanism of their effectiveness remains largely unexplored. In the present study, we confirmed that the protective effects of MSCs on mouse model of acute liver failure (ALF) were based on MSC-secreted prostaglandin (PG)E2 . Our data confirmed that MSC-secreted PGE2 not only inhibited apoptosis but also enhanced hepatocyte proliferation, thus attenuating ALF...
September 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
A Baranova, D Maltseva, A Tonevitsky
Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology. Here we propose tissue-cooperative, homeostatic model of NAFLD. During early stages of NAFLD the intrahepatic production of miR-122 falls, while the secretion of miRNA-containing exosomes by adipose increases. Bloodstream carries exosome to the liver, where their miRNA cargo is released to regulate their intrahepatic targets. When the deterioration of adipose catches up with the failing hepatic parenchyma, the external supply of liver-supporting miRNAs gradually tapers off, leading to the fibrotic decompensation of the liver and an increase in hepatic carcinogenesis...
September 24, 2018: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Junyu Fan, Xiaojun Tang, Qian Wang, Zhuoya Zhang, Shufang Wu, Wenchao Li, Shanshan Liu, Genhong Yao, Hongwei Chen, Lingyun Sun
BACKGROUND: Mesenchymal stem cells (MSCs) play an anti-inflammatory role by secreting certain bioactive molecules to exert their therapeutic effects for disease treatment. However, the underlying mechanism of MSCs in chronic autoimmune liver diseases-primary biliary cholangitis (PBC), for example-remains to be elucidated. METHODS: Human umbilical cord-derived MSCs (UC-MSCs) were injected intravenously into 2-octynoic acid coupled to bovine serum albumin (2OA-BSA)-induced autoimmune cholangitis mice...
September 17, 2018: Stem Cell Research & Therapy
Yanning Liu, Guohua Lou, Aichun Li, Tianbao Zhang, Jinjin Qi, Dan Ye, Min Zheng, Zhi Chen
BACKGROUND: Mesenchymal stem cell (MSC)-derived exosome administration has been considered as a novel cell-free therapy for liver diseases through cell-cell communication. This study was aimed to determine the effects and mechanisms of AMSC-derived exosomes (AMSC-Exo) for acute liver failure (ALF) treatment. METHODS: AMSC-Exo were intravenously administrated into the mice immediately after lipopolysaccharide and D-galactosamine (LPS/GalN)-exposure and their effects were evaluated by liver histological and serum biochemical analysis...
September 6, 2018: EBioMedicine
Xujing Liang, Taoyuan Li, Qiuchan Zhou, Sainan Pi, Yadan Li, Xiaojia Chen, Zeping Weng, Hongmei Li, Ying Zhao, Huadong Wang, Youpeng Chen
Sepsis is a leading cause of death in intensive care units that can result in acute hepatic damage. Animal experiments and clinical trials have shown that mesenchymal stem cell (MSC) therapy has some beneficial in several liver diseases. However, the protective effects of MSC therapy on sepsis-induced hepatic damage and associated mechanisms are not completely understood. The aim of the present study was to investigate the effects of MSCs on sepsis-induced liver injury and underlying mechanisms. A rat model of sepsis-induced liver injury was established by cecal ligation and puncture, and serum alanine aminotransferase and aspartate transaminase activities as well as liver histological changes were measured...
September 3, 2018: Molecular and Cellular Biochemistry
Yong-Hong Wang, Dong-Bo Wu, Bing Chen, En-Qiang Chen, Hong Tang
Acute liver failure is a life-threatening clinical syndrome characterized by rapid development of hepatocellular necrosis leading to high mortality and resource costs. Numerous treatment strategies for acute liver failure simply prevent complications and decelerate disease progression. The only curative treatment for acute liver failure is liver transplantation, but there are many restrictions on the application of liver transplantation. In recent years, a growing number of studies have shown that stem cells can effectively treat acute liver failure...
August 24, 2018: Stem Cell Research & Therapy
Jun Lei, Yong Chai, Juhua Xiao, Huakun Hu, Zhiqiang Liu, Yu Xiao, Lijun Yi, Jinshi Huang, Tianxin Xiang, Shouhua Zhang
Biliary atresia (BA) is a rare and severe disease that affects infants where a fibroinflammatory process destroys the bile ducts, leading to fibrosis and biliary cirrhosis, and mortality if untreated. Bone marrow‑derived mesenchymal stem cells (BMMSCs) have been considered as a promising therapy in fibrotic diseases. The aim of the present was to investigate the anti‑fibrotic roles of BMMSC transplantation in a BA mouse model. Mouse BA models were established by Rhesus rotavirus administration to neonatal mice...
August 3, 2018: Molecular Medicine Reports
Guo Chao Niu, Lei Liu, Libo Zheng, Hong Zhang, David Q Shih, Xiaolan Zhang
BACKGROUND: A variety of extra-intestinal manifestations (EIMs), including hepatobiliary complications, are associated with inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) have been shown to play a potential role in the therapy of IBD. This study was designed to investigate the effect and mechanism of MSCs on chronic colitis-associated hepatobiliary complications using mouse chronic colitis models induced by dextran sulfate sodium (DSS). METHODS: DSS-induced mouse chronic colitis models were established and treated with MSCs...
August 13, 2018: BMC Gastroenterology
Ryo Sugiura, Shunsuke Ohnishi, Masatsugu Ohara, Marin Ishikawa, Shuichi Miyamoto, Reizo Onishi, Koji Yamamoto, Kazumichi Kawakubo, Masaki Kuwatani, Naoya Sakamoto
Mesenchymal stem cells (MSCs) represent a valuable cell source in regenerative medicine, and large numbers of MSCs can be isolated from the amnion noninvasively. Sclerosing cholangitis is a chronic cholestatic disease and characterized by progressive biliary destruction leading to cirrhosis. Many factors are involved in the development of sclerosing cholangitis; however, effective medical therapy is not established. We investigated the effects of human amnion-derived MSCs (hAMSCs) and conditioned medium (CM) obtained from hAMSC cultures in rats with sclerosing cholangitis...
2018: American Journal of Translational Research
Antonia Graja, Francisco Garcia-Carrizo, Anne-Marie Jank, Sabrina Gohlke, Thomas H Ambrosi, Wenke Jonas, Siegfried Ussar, Matthias Kern, Annette Schürmann, Krasimira Aleksandrova, Matthias Blüher, Tim J Schulz
Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described...
October 2018: Aging Cell
Yogeshwar Sharma, Jinghua Liu, Kathleen E Kristian, Antonia Follenzi, Sanjeev Gupta
Background: In Wilson's disease, ATP7B mutations impair copper excretion with liver or brain damage. Healthy transplanted hepatocytes repopulate liver, excrete copper and reverse hepatic damage in animal models of Wilson's disease. In Fah-/- mice with tyrosinemia and alpha-1 antitrypsin mutant mice, liver disease is resolved by expansions of healthy hepatocytes derived from transplanted healthy bone marrow stem cells. This potential of stem cells has not been defined for Wilson's disease. Methods: In diseased Atp7b-/- mice we reconstituted bone marrow with donor cells expressing green fluorescent protein reporter from healthy transgenic mice...
July 20, 2018: Gene Expression
Hwansu Kang, Eunhui Seo, Jong-Moon Park, Na-Young Han, Hookeun Lee, Hee-Sook Jun
Mesenchymal stem cells (MSCs) have been investigated to treat liver diseases, but the efficiency of MSCs to treat chronic liver diseases is conflicting. FGF21 can reduce inflammation and fibrosis. We established FGF21-secreting adipose derived stem cells (FGF21_ADSCs) to enhance the effects of ADSCs and transplanted them into thioacetamide (TAA)-induced liver fibrosis mice via the tail vein. Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis-related factors such as α-smooth muscle actin (α-SMA), collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with the Empty_ADSCs by inhibition of p-JNK, NF-κB and p-Smad2/3 signalling...
October 2018: Journal of Cellular and Molecular Medicine
Ran Xue, Qinghua Meng, Juan Li, Jing Wu, Qinwei Yao, Hongwei Yu, Yueke Zhu
Acute-on-chronic liver failure (ACLF) is a serious life-threatening disease with high prevalence. Liver transplantation is the only efficient clinical treatment for ACLF. Because of the rapid progression and lack of liver donors, it is urgent to find an effective and safe therapeutic approach to ACLF. Recent studies showed that multipotent cell transplantation could improve the patients' liver function and enhance their preoperative condition. Cells such as mesenchymal stem cells, bone marrow mononuclear cells and autologous peripheral blood stem cells, which addressed in this study have all been used in multipotent cell transplantation for liver diseases...
October 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Friederike Rohn, Claus Kordes, Mirco Castoldi, Silke Götze, Gereon Poschmann, Kai Stühler, Diran Herebian, Amelie S Benk, Fania Geiger, Tingyu Zhang, Joachim P Spatz, Dieter Häussinger
The laminin α5 protein chain is an element of basement membranes and important to maintain stem cells. Hepatic stellate cells (HSC) are liver-resident mesenchymal stem cells, which reside in a quiescent state on a basement membrane-like structure in the space of Dissé. In the present study, laminin α5 chain was detected in the space of Dissé of normal rat liver. Since HSC are critical for liver regeneration and can contribute to fibrosis in chronic liver diseases, the effect of laminins on HSC maintenance was investigated...
October 2018: Biomaterials
Mercedes Lopez-Santalla, Pablo Mancheño-Corvo, Amelia Escolano, Ramon Menta, Olga Delarosa, Juan M Redondo, Juan A Bueren, Wilfried Dalemans, Eleuterio Lombardo, Marina I Garin
Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. The immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless of the route of administration used, the inflammation conditions and the major histocompatibility complex context. These observations raise the question of whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect...
June 23, 2018: International Journal of Molecular Sciences
Esteban Juan Fiore, Luciana María Domínguez, Juan Bayo, Mariana Gabriela García, Guillermo Daniel Mazzolini
Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells (MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise, it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles (EVs)...
June 21, 2018: World Journal of Gastroenterology: WJG
Ya-Bin Yu, Yan Song, Ya Chen, Feng Zhang, Fu-Zhen Qi
Mesenchymal stem cells (MSCs) are considered to be an ideal source for the cell therapy of end‑stage liver diseases. Umbilical cord (UC)‑MSCs can be obtained via a non‑invasive procedure and can be easily cultured, making them potentially superior candidates for cell transplantation when compared with MSCs from other sources. In the present study, UC‑MSCs were induced to differentiate into hepatocytes and were compared with bone marrow (BM)‑MSCs for their hepatic differentiation potential. UC‑MSCs showed significantly higher proliferation than BM‑MSCs...
August 2018: Molecular Medicine Reports
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