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mesenchymal stem cells in liver disease

Yanhong Li, Di Zhang, Ling Xu, Lin Dong, Ji Zheng, Yikong Lin, Jiefang Huang, Yanyun Zhang, Yu Tao, Xingxing Zang, Dajin Li, Meirong Du
Mesenchymal stem cells (MSCs), which are pluripotent cells with immunomodulatory properties, have been considered good candidates for the therapy of several immune disorders, such as inflammatory bowel diseases, concanavalin A-induced liver injury, and graft-versus-host disease. The embryo is a natural allograft to the maternal immune system. A successful pregnancy depends on the timely extinction of the inflammatory response induced by embryo implantation, followed by the switch to a tolerant immune microenvironment in both the uterus and the system...
February 18, 2019: Cellular & Molecular Immunology
Kiyohito Yagi
This review reflects back over almost 40 years of the author's basic research conducted at Graduate School of Pharmaceutical Sciences, Osaka University, Japan. After performing postdoctoral research in USA, the author became a research associate at Prof. Yoshiharu Miura's lab and started research on Biochemical Engineering in 1984. At that time, the main research purpose was to solve global environmental issues for maintaining human health. The author's achievements included novel useful material production system under inorganic conditions and genetically engineered whole-cell bacterial sensors detecting arsenite by naked eye without a detecting device...
2019: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Lunzhi Yuan, Jing Jiang, Xuan Liu, Yali Zhang, Liang Zhang, Jiaojiao Xin, Kun Wu, Xiaoling Li, Jiali Cao, Xueran Guo, Dongyan Shi, Jun Li, Longyan Jiang, Suwan Sun, Tengyun Wang, Wangheng Hou, Tianying Zhang, Hua Zhu, Jun Zhang, Quan Yuan, Tong Cheng, Jun Li, Ningshao Xia
OBJECTIVE: Developing a small animal model that accurately delineates the natural history of hepatitis B virus (HBV) infection and immunopathophysiology is necessary to clarify the mechanisms of host-virus interactions and to identify intervention strategies for HBV-related liver diseases. This study aimed to develop an HBV-induced chronic hepatitis and cirrhosis mouse model through transplantation of human bone marrow mesenchymal stem cells (hBMSCs). DESIGN: Transplantation of hBMSCs into Fah-/- Rag2-/- IL-2Rγc-/- SCID (FRGS) mice with fulminant hepatic failure (FHF) induced by hamster-anti-mouse CD95 antibody JO2 generated a liver and immune cell dual-humanised (hBMSC-FRGS) mouse...
January 30, 2019: Gut
Sara A Mohamed, Shahinaz Shalaby, Soumia Brakta, Lelyand Elam, Amro Elsharoud, Ayman Al-Hendy
BACKGROUND: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. MATERIALS AND METHOD: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions...
January 18, 2019: Biomedicines
Lei Cao, Yan Zhang, Mengyuan Qian, Xueping Wang, Qizhi Shuai, Chao Gao, Ren Lang, Jun Yang
The differentiation of human mesenchymal stem cells (hMSCs) into hepatocyte-like cells in vitroprovides a promising candidate for cell therapy of liver diseases, and cell aggregates have been proposed to improve the efficiency of expansion and differentiation. Previously, we engineered multicellular aggregates incorporating human E-cadherin fusion protein (hE-cad-Fc)-coated poly(lactic-co-glycolic acid) (PLGA) microparticles (hE-cad-PLGAs), and a significant improvement was obtained in both cellular proliferation of and cytokine secretion by hMSCs...
January 17, 2019: Acta Biomaterialia
Jiefang Huang, Xiaonan Zhao, Jian Wang, Yiji Cheng, Qiong Wu, Bei Wang, Fang Zhao, Lijun Meng, Yanyun Zhang, Min Jin, Huanbai Xu
BACKGROUND: Fully understanding the developmental process of hepatic stem cells (HSCs) and the mechanisms of their committed differentiation is essential for optimizing the generation of functional hepatocytes for cell therapy in liver disease. Delta-like 1 homolog (Dlk1), primarily the membrane-bound form (Dlk1M ), is generally used as a surface marker for fetal hepatic stem cell isolation, while its soluble form (Dlk1S ) and the functional roles of different Dlk1 isoforms in HSC differentiation remain to be investigated...
January 15, 2019: Stem Cell Research & Therapy
Saifun Nahar, Yoshiki Nakashima, Chika Miyagi-Shiohira, Takao Kinjo, Zensei Toyoda, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi, Jiro Fujita
Adipose-derived mesenchymal stem cells (ADSCs) are a treatment cell source for patients with chronic liver injury. ADSCs are characterized by being harvested from the patient's own subcutaneous adipose tissue, a high cell yield ( i.e ., reduced immune rejection response), accumulation at a disease nidus, suppression of excessive immune response, production of various growth factors and cytokines, angiogenic effects, anti-apoptotic effects, and control of immune cells via cell-cell interaction. We previously showed that conditioned medium of ADSCs promoted hepatocyte proliferation and improved the liver function in a mouse model of acute liver failure...
November 26, 2018: World Journal of Stem Cells
Lijun Chen, Jingjing Qu, Charlie Xiang
Menstrual blood-derived stem cells (MenSCs) are a novel source of mesenchymal stem cells (MSCs). MenSCs are attracting more and more attention since their discovery in 2007. MenSCs also have no moral dilemma and show some unique features of known adult-derived stem cells, which provide an alternative source for the research and application in regenerative medicine. Currently, people are increasingly interested in their clinical potential due to their high proliferation, remarkable versatility, and periodic acquisition in a non-invasive manner with no other sources of MSCs that are comparable in adult tissue...
January 3, 2019: Stem Cell Research & Therapy
Sugandha Saxena, Abhilasha Purohit, Michelle L Varney, Yuri Hayashi, Rakesh K Singh
BACKGROUND: Pancreatic cancer (PC) is a highly aggressive disease, and the lethality of this disease stems from early metastatic dissemination where surgical removal cannot provide a cure. Improvement of the therapeutic outcome and overall survival of PC patients requires to understand the fundamental processes that lead to metastasis such as the gain of cellular migration ability. One such family of proteins, which are essential players of cellular migration, is Semaphorin. Previously, we have identified one of the Semaphorin family member, Semaphorin-5A (SEMA5A) to be involved in organ-specific homing during PC metastasis...
December 22, 2018: BMC Cancer
Chiara Gardin, Letizia Ferroni, Gloria Bellin, Giuseppe Rubini, Simone Barosio, Barbara Zavan
Currently, the most effective therapy for liver diseases is liver transplantation, but its use is limited by organ donor shortage, economic reasons, and the requirement for lifelong immunosuppression. Mesenchymal stem cell (MSC) transplantation represents a promising alternative for treating liver pathologies in both human and veterinary medicine. Interestingly, these pathologies appear with a common clinical and pathological profile in the human and canine species; as a consequence, dogs may be a spontaneous model for clinical investigations in humans...
December 15, 2018: International Journal of Molecular Sciences
Christopher Newell, Rasha Sabouny, Dustin S Hittel, Timothy E Shutt, Aneal Khan, Matthias S Klein, Jane Shearer
Mesenchymal stem cells (MSCs) are the most commonly used cells in tissue engineering and regenerative medicine. MSCs can promote host tissue repair through several different mechanisms including donor cell engraftment, release of cell signaling factors, and the transfer of healthy organelles to the host. In the present study, we examine the specific impacts of MSCs on mitochondrial morphology and function in host tissues. Employing in vitro cell culture of inherited mitochondrial disease and an in vivo animal experimental model of low-grade inflammation (high fat feeding), we show human-derived MSCs to alter mitochondrial function...
2018: Frontiers in Physiology
Alissa C Greenwald, Tamar Licht, Saran Kumar, Sunday S Oladipupo, Seema Iyer, Myriam Grunewald, Eli Keshet
Insufficient erythropoiesis due to increased demand is usually met by hypoxia-driven up-regulation of erythropoietin (Epo). Here, we uncovered vascular endothelial growth factor (VEGF) as a novel inducer of Epo capable of increasing circulating Epo under normoxic, nonanemic conditions in a previously unrecognized reservoir of Epo-producing cells (EPCs), leading to expansion of the erythroid progenitor pool and robust splenic erythropoiesis. Epo induction by VEGF occurs in kidney, liver, and spleen in a population of Gli1+ SMA+ PDGFRβ+ cells, a signature shared with vascular smooth muscle cells (VSMCs) derived from mesenchymal stem cell-like progenitors...
December 13, 2018: Journal of Experimental Medicine
Yichi Zhang, Ruini Li, Weiwei Rong, Mingzi Han, Chenghu Cui, Zhenning Feng, Xiaoli Sun, Shizhu Jin
Hepatocirrhosis is one of the most severe complications of chronic hepatic disease in terms of medical intervention, and the available therapies are limited and not very successful. In this study, bone marrow-derived mesenchymal stem cells (BM-MSCs) from host rats were transduced with an adenoviral vector labelled with green fluorescent protein (EGFP) to overexpress hepatocyte growth factor (HGF). The therapeutic effect of these modified stem cells (HGF-BM-MSC group) transplanted intravenously into hepatocirrhosis model rats treated with CCl4 was evaluated using serological, biochemical and histological approaches...
December 11, 2018: Cell Death & Disease
Jun Zheng, Hui Li, Liying He, Yiming Huang, Jianye Cai, Liang Chen, Chaorong Zhou, Hongyuan Fu, Tongyu Lu, Yingcai Zhang, Jia Yao, Yang Yang
OBJECTIVES: Transfusion of umbilical cord-derived mesenchymal stem cells (UC-MSCs) is a novel strategy for treatment of various liver diseases. However, the therapeutic effect of UC-MSCs is limited because only a few UC-MSCs migrate towards the damaged regions. In this study, we observed the effects of autophagy on the migration of UC-MSCs in vitro and in a model of liver ischaemia/reperfusion (I/R) injury. MATERIALS AND METHODS: We investigated the effects of autophagy on the status of the cell, release of anti-inflammatory factors and migration of UC-MSCs in vitro...
December 10, 2018: Cell Proliferation
Kaveh Baghaei, Samaneh Tokhanbigli, Hamid Asadzadeh, Saeed Nmaki, Mohammad Reza Zali, Seyed Mahmoud Hashemi
Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy...
December 7, 2018: Journal of Cellular Physiology
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
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