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mesenchymal stem cells in liver disease

Ruveena Rajaram, Baskar Subramani, Basri J J Abdullah, Sanjiv Mahadeva
Mesenchymal stem cell (MSC) transplant may offer an alternative to liver transplantation in patients with end-stage liver disease. However, its efficacy remains uncertain. MSC was performed on a 50-year-old male with decompensated (Child-Turcotte-Pugh grade C) alcoholic liver cirrhosis due to an absence of donors for adult-deceased and living-related liver transplantation. Autologous bone marrow-derived MSCs were harvested from the patient and cultured using standard protocols. The MSCs were subsequently re-administrated into the liver via hepatic intra-arterial infusion on two separate occasions...
December 2017: JGH open: an open access journal of gastroenterology and hepatology
Guanguan Qiu, Guoping Zheng, Menghua Ge, Jiangmei Wang, Ruoqiong Huang, Qiang Shu, Jianguo Xu
Mesenchymal stem cells (MSCs) are adult stromal cells with the capacity to differentiate into multiple types of cells. MSCs represent an attractive option in regenerative medicine due to their multifaceted abilities for tissue repair, immunosuppression, and anti-inflammation. Recent studies demonstrate that MSCs exert their effects via paracrine activity, which is at least partially mediated by extracellular vesicles (EVs). MSC-derived EVs (MSC-EVs) could mimic the function of parental MSCs by transferring their components such as DNA, proteins/peptides, mRNA, microRNA (miRNA), lipids, and organelles to recipient cells...
November 21, 2018: Stem Cell Research & Therapy
Kuo-Jen Wu, Seong-Jin Yu, Chia-Wen Chiang, Yu-Wei Lee, B Linju Yen, Chun-Sen Hsu, Li-Wei Kuo, Yun Wang
Increasing evidence have supported that Wharton's jelly mesenchymal stem cell (WJ-MSCs) have immunomodulatory and protective effects against several diseases including kidney, liver pathologies, and heart injury. Few in vitro studies have reported that WJ-MSCs reduced inflammation in hippocampal slices after oxygen-glucose deprivation. We recently reported the neuroprotective effects of human WJ-MSCs (hWJ-MSCs) in rats exposed to a transient right middle cerebral artery occlusion. hWJ-MSCs transplantation significantly reduced brain infarction and microglia activation in the penumbra leading with a significant reduction of neurological deficits...
July 2018: Brain Circulation
L-Y Wang, L-P Liu, J-Y Ge, Y-Y Yuan, L-L Sun, H Xu, P-Y Huang, L-J Hui, H Isoda, N Ohkohchi, Y-M Li, Y-W Zheng
OBJECTIVES: The difficulty in proliferation and availability and the rapid loss functions of primary human hepatocytes highlight the need to develop an alternative, preferably renewable source of human induced hepatocytes in regenerative medicine. Liver organoids generated on a multiple-cell microenvironment in a 3-dimensional (3D) system can provide a highly efficient solution to this issue. METHODS: Human hepatocytes were induced from fibroblasts by the lentiviral expression of FOXA3, HNF1A, and HNF4A...
November 2018: Transplantation Proceedings
Abhisek Mitra, Jun Yan, Liangfang Zhang, Shulin Li
Liver is the second most transplanted organ according to United network for organ sharing. Due to shortage of compatible donors, surgical difficulties, immunological hindrance, and high postoperative cost, stem cell therapy is an attractive substitute of liver transplant for millions of patients suffering from hepatic failure. Due to several technical limitations such as viral integration, inefficient differentiation, and adult phenotypes and epigenetic memory of fibroblasts, induced pluripotent stem cells, mesenchymal stem cells, or induced hepatocyte may not present a great clinical substitute for liver transplant...
October 19, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Shogo Ohkoshi, Haruka Hirono, Taka Nakahara, Hiroshi Ishikawa
Mesenchymal stem cells (MSCs) as a source for regenerative medicine are now the subject of much clinical attention. There are high expectations due to their safety, low tumorigenic risk, and low ethical concerns. MSC therapy has been approved for acute graft-versus host diseases since 2015. Tooth-derived MSCs are known to have a great potential in their proliferation and differentiation capacities, even when compared with bone-marrow-derived MSCs. In particular, stem cells from human exfoliated deciduous teeth (SHEDs) are the best candidates for personal cell banking (dental pulp cell bank), because they can be obtained less invasively in the natural process of individual growth...
October 27, 2018: World Journal of Hepatology
Jia Fang, Yuan Yan, Xin Teng, Xinyu Wen, Na Li, Sha Peng, Wenshuai Liu, F Xavier Donadeu, Shanting Zhao, Jinlian Hua
Transplantation of adipose-derived mesenchymal stem cells (ADMSCs) can aid in the treatment of numerous diseases in animals. However, natural aging during in vitro expansion of ADMSCs prior to their use in transplantation restricts their beneficial effects. Melatonin is reported to exert biorhythm regulation, anti-oxidation, and anti-senescence effects in various animal and cell models. Herein, by using a senescent canine ADMSCs (cADMSCs) cell model subjected to multiple passages in vitro , we investigated the effects of melatonin on ADMSCs senescence...
October 25, 2018: Aging
Shimaa Farouk, Salwa Sabet, Fatma A Abu Zahra, Akmal A El-Ghor
Therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been reported in several animal models of liver fibrosis. Interleukin (IL) 17A, IL6 and Stat3 have been described to play crucial roles in chronic liver injury. However, the modulatory effect of MSCs on these markers was controversial in different diseases. BM-MSCs might activate the IL6/STAT3 signaling pathway and promote cell invasion in hepatocellular carcinoma, but the immunomodulatory role of BM-MSCs on IL17A/IL6/STAT3 was not fully elucidated in liver fibrosis...
2018: PloS One
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 C 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 this study, the Gunn rat was used as an animal model for heritable liver dysfunction. Induced mesenchymal stem cells (iMSCs) 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...
November 20, 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...
November 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...
October 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
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