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Mesenchymal stem cells, liver, pig

Dongyan Shi, Jianing Zhang, Qian Zhou, Jiaojiao Xin, Jing Jiang, Longyan Jiang, Tianzhou Wu, Jiang Li, Wenchao Ding, Jun Li, Suwan Sun, Jianzhou Li, Ning Zhou, Liyuan Zhang, Linfeng Jin, Shaorui Hao, Pengcheng Chen, Hongcui Cao, Mingding Li, Lanjuan Li, Xin Chen, Jun Li
OBJECTIVE: Stem cell transplantation provides a promising alternative for the treatment of fulminant hepatic failure (FHF). However, it lacks fundamental understanding of stem cells' activities. Our objective was to clarify stem cell-recipient interactions for overcoming barriers to clinical application. DESIGN: We used an in-house large-animal (pig) model of FHF rescue by human bone marrow mesenchymal stem cells (hBMSCs) and profiled the cells' activities. The control and transplantation groups of pigs (n=15 per group) both received a D-galactosamine (D-Gal) injection (1...
February 16, 2016: Gut
Chenxia Hu, Ning Zhou, Jianzhou Li, Ding Shi, Hongcui Cao, Jun Li, Lanjuan Li
Acute liver failure (ALF) is a kind of complicated syndrome. Furthermore, adipose-derived mesenchymal stem cells (ADMSCs) can serve as a useful cell resource for autotransplantation due to their abundance and micro-invasive accessability. However, it is unknown how ALF will influence the characteristics of ADMSCs and whether ADMSCs from patients suffering from end-stage liver diseases are potential candidates for autotransplantation. This study was designed to compare various properties of ALF-derived ADMSCs with normal ADMSCs in pig models, with regard to their cellular morphology, cell proliferative ability, cell apoptosis, expression of surface antigens, mitochondrial and lysosomal activities, multilineage potency, and expression of liver-specific genes...
January 5, 2016: International Journal of Molecular Sciences
Chunyu Bai, Shuming Chen, Yuhua Gao, Zhiqiang Shan, Weijun Guan, Yuehui Ma
Bone marrow mesenchymal stem cells (BMSCs) are easy to obtain and thought to be ideal candidate cells for reconstruction of tissues and organs. Pigs are an appropriate animal model because their physiological structure, organ size, nutritional metabolism, and pathological reactions are similar to those of humans. In this study, bone marrow was collection from Bama miniature pigs to isolate BMSCs (B-BMSCs) by whole bone marrow culture method. We then examined their biological characteristics such as growth kinetics, surface antigen, and multi-lineage potential...
December 2015: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Hongchen Ji, Xiao Li, Shuqiang Yue, Junjie Li, Hui Chen, Zhuochao Zhang, Ben Ma, Jing Wang, Meng Pu, Liang Zhou, Chong Feng, Desheng Wang, Juanli Duan, Dengke Pan, Kaishan Tao, Kefeng Dou
BACKGROUND: The activation of tissue factor (TF) is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI) is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. METHODS: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility...
2015: Cellular Physiology and Biochemistry
Jiaojiao Xin, Wenchao Ding, Shaorui Hao, Longyan Jiang, Qian Zhou, Tianzhou Wu, Dongyan Shi, Hongcui Cao, Lanjuan Li, Jun Li
BACKGROUND & AIMS: Human bone marrow mesenchymal stem cell (hBMSC) transplantation is expected to become an alternative regenerative technique for liver diseases. However, the mechanism by which hBMSCs differentiate into hepatocytes is still unclear. The aim of this study was to establish the specific characteristics of hBMSC-derived hepatocytes (hBMSC-Heps) for future clinical applications. METHODS: Potential hBMSC-Hep biomarkers were screened using cytokine arrays...
October 2015: Liver International: Official Journal of the International Association for the Study of the Liver
Tuomas Mäkelä, Reijo Takalo, Oiva Arvola, Henri Haapanen, Fredrik Yannopoulos, Roberto Blanco, Lauri Ahvenjärvi, Kai Kiviluoma, Erja Kerkelä, Johanna Nystedt, Tatu Juvonen, Petri Lehenkari
BACKGROUND AIMS: Bone marrow mononuclear cells (BM-MNCs) and bone marrow-derived mesenchymal stem stromal cells (BM-MSCs) could have therapeutic potential for numerous conditions, including ischemia-related injury. Cells transplanted intravascularly may become entrapped in the lungs, which potentially decreases their therapeutic effect and increases the risk for embolism. METHODS: Twelve pigs were divided into groups of 3 and received (99m)Tc- hydroxymethyl-propylene-amine-oxime-labeled autologous BM-MNCs or allogeneic BM-MSCs by either intravenous (IV) or intra-arterial (IA) transplantation...
April 2015: Cytotherapy
Sandra Brückner, Hans-Michael Tautenhahn, Sandra Winkler, Peggy Stock, Matthias Dollinger, Bruno Christ
STUDY BACKGROUND: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals...
February 15, 2014: Experimental Cell Research
Rony Avritscher, Mohamed E Abdelsalam, Sanaz Javadi, Joe Ensor, Michael J Wallace, Eckhard Alt, David C Madoff, Jody V Vykoukal
PURPOSE: To investigate the safety and effectiveness of a novel endovascular approach for therapeutic cell delivery using a balloon occlusion catheter in a large animal model of liver fibrosis. MATERIALS AND METHODS: Transcatheter arterial embolization with ethiodized oil (Ethiodol) and ethanol was used to induce liver damage in 11 pigs. Mesenchymal stem cells (MSCs) were harvested from adipose tissue and engineered to express green fluorescent protein (GFP). A balloon occlusion catheter was positioned in the bilateral first-order portal vein branches 2 weeks after embolization to allow intraportal application of MSCs in six experimental animals...
December 2013: Journal of Vascular and Interventional Radiology: JVIR
Jiang-Qiang Xiao, Xiao-Lei Shi, Jia-Jun Tan, Ling Zhang, Qian Xu, Yi-Tao Ding
OBJECTIVE: To evaluate whether a combination therapy using allogeneic mesenchymal stem cell (MSC) transplantation and interleukin-1 receptor antagonist (IL-1Ra) chitosan nanoparticles is more robust than MSC transplantation alone for treating acute liver failure and to investigate the mechanisms of the improved therapeutic effect using a swine model system. METHODS: IL-1Ra-loaded nanoparticles were made of lactosylated chitosan-FITC using the electrostatic spray method and analyzed by enzyme-linked immunosorbent assay...
April 2013: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Eiji Kobayashi, Shuji Hishikawa, Takumi Teratani, Alan T Lefor
To improve the welfare of experimental animals, investigators seek to respect the 3R principle (Replacement, Reduction, and Refinement). Even when large animal studies are essential before moving to clinical trials, it is important to look for ways to reduce the number of experimental animals used. At the Center for the Development of Advanced Medical Technology, we consider 'medical' pigs to be ideal preclinical model systems.We have been using both wild-type and genetically modified pigs. We began using this approach about 10 years ago with a 'total pig system' to model human health and disease for the purposes of both medical skill education and the development of new devices and therapeutic strategies...
2012: Transplantation Research
N C Talbot, T J Caperna, W M Garrett
Totipotent embryonic stem cell lines have not been established from ungulates; however, we have developed a somatic stem cell line from the in vitro culture of pig epiblast cells. The cell line, ARS-PICM-19, was isolated via colony cloning and was found to spontaneously differentiate into hepatic parenchymal epithelial cell types, namely hepatocytes and bile duct cells. Hepatocytes form as monolayers and bile duct cells as 3-dimensional bile ductules. Transmission electron microscopy revealed that the ductules were composed of radially arranged, monociliated cells with their cilia projecting into the lumen of the ductule whereas hepatocytes were arranged in monolayers with lateral canalicular structures containing numerous microvilli and connected by tight junctions and desmosomes...
January 2013: Journal of Animal Science
J M Abellaneda, G Ramis, L Martínez-Alarcón, M J Majado, J J Quereda, J M Herrero-Medrano, L Mendonça, O García-Nicolás, M Reus, C Insausti, A Ríos, A López-Navas, M R González, F J Pallarés, A Munoz, P Ramírez, P Parrilla
OBJECTIVE: Using a percutaneous ecoguided injection system to obtain chimeric piglets through a less invasive and traumatic technique than previously reported. MATERIALS AND METHODS: The two types of human cells included umbilical cord blood mononuclear elements and mesenchymal stem cells cultured from bone marrow. Four sows at gestational day 50 were anesthetized. A needle was inserted through the skin and uterine wall to reach the peritoneal cavity of the fetuses under continuous ultrasound guidance...
July 2012: Transplantation Proceedings
Hongcui Cao, Jinfeng Yang, Jiong Yu, Qiaoling Pan, Jianzhou Li, Pengcheng Zhou, Yanyuan Li, Xiaoping Pan, Jun Li, Yingjie Wang, Lanjuan Li
BACKGROUND: Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs) and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF). METHODS: hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation...
2012: BMC Medicine
Jun Li, Jiaojiao Xin, Shaorui Hao, Liyuan Zhang, Longyan Jiang, Deying Chen, Qing Xie, Wei Xu, Hongcui Cao, Lanjuan Li
Our recent study first demonstrated that human bone marrow mesenchymal stem cell (hBMSC) transplantation could prevent death from fulminant hepatic failure (FHF) in pigs. To further clarify the metabolic mechanism of hBMSC transplantation in FHF, the plasma collected from FHF pigs that received transplantation of hBMSCs was examined using metabolic analysis to identify the key molecular markers that regulate recovery. The results showed that obvious metabolic disturbance occurred during FHF, whereas the hBMSC transplantation group showed less severe liver injury...
June 1, 2012: Journal of Proteome Research
Jun Li, Liyuan Zhang, Jiaojiao Xin, Longyan Jiang, Jun Li, Ting Zhang, Linfeng Jin, Jianzhou Li, Pengcheng Zhou, Shaorui Hao, Hongcui Cao, Lanjuan Li
UNLABELLED: The effectiveness of human bone marrow mesenchymal stem cell (hBMSC) transplantation to treat acute and chronic liver injury has been demonstrated in animal models and in a few nonrandomized clinical trials. However, no studies have investigated hBMSC transplantation in the treatment of fulminant hepatic failure (FHF), especially in large animal (pig) models. The aim of this study was to demonstrate the safety, effectiveness, and underlying mechanism of hBMSC transplantation for treating FHF in pigs through the intraportal route...
September 2012: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ariane Groth, Sabine Ottinger, Christian Kleist, Elisabeth Mohr, Mohammad Golriz, Daniel Schultze, Helge Bruns, Arianeb Mehrabi, Peter Schemmer, Markus W Büchler, Ingrid Herr
Mesenchymal stem cell (MSC) transplantation is suggested for therapy of end-stage liver disease, due to e.g. liver cancer and metastasis. Liver transplantation is the only therapeutic option so far but donor organs are short. Also, the availability of allogeneic human MSCs for liver regeneration is limited. Therefore, we evaluated the suitability of porcine bone marrow MSCs from semi-adult pigs and found that morphology, surface expression pattern and multilineage differentiation are similar to those of human MSCs...
February 2012: International Journal of Oncology
Minjie Lu, Shihua Zhao, Qiong Liu, Shiliang Jiang, Peng Song, Haiyan Qian, Yan Zhang, Jian Ling, Chaowu Yan, Huaibing Cheng, Ning Ma, Hong Zhao, Yuqing Liu
PURPOSE: The purpose of this study was to track and investigate the effects of autologous bone marrow-derived mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction in swine assessed by magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twenty-four Chinese mini-pigs (27±3 kg) were divided into 4 groups, including control groups (groups 1 and 3) and MSCs transplantation groups (group 2, super paramagnetic iron oxide labeled and group 4, 4',6-diamidino-2-phenylindole labeled)...
March 2012: Journal of Thoracic Imaging
Xiao-Lei Shi, Jin-Yang Gu, Bing Han, Hai-Yun Xu, Liang Fang, Yi-Tao Ding
AIM: To evaluate tracking of magnetically labeled mesenchymal stem cells (MSCs) after intraportal transplantation. METHODS: Mononuclear cells were isolated from bone marrow aspirates of pigs by density gradient centrifugation, cultured and expanded, after which, they were incubated with super paramagnetic iron oxide (SPIO). Prussian blue staining was performed to highlight intracellular iron. To establish swine models of acute liver injury, 0.5 g/kg D-galactosamine was administrated to 10 pigs, six of which were injected via their portal veins with SPIO-labeled MSCs, while the remaining four were injected with unlabeled cells...
August 7, 2010: World Journal of Gastroenterology: WJG
Ruenn Chai Lai, Fatih Arslan, Soon Sim Tan, Betty Tan, Andre Choo, May May Lee, Tian Sheng Chen, Bao Ju Teh, John Kun Long Eng, Harwin Sidik, Vivek Tanavde, Wei Sek Hwang, Chuen Neng Lee, Reida Menshawe El Oakley, Gerard Pasterkamp, Dominique P V de Kleijn, Kok Hian Tan, Sai Kiang Lim
The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives. Here we derived five MSC cultures from limb, kidney and liver tissues of three first trimester aborted fetuses and like our previously described hESC-derived MSCs; they were highly expandable and had similar telomerase activities...
June 2010: Journal of Molecular and Cellular Cardiology
Alain J Poncelet, Dufrane Denis, Pierre Gianello
PURPOSE OF REVIEW: Expectations are high on cellular therapy. Being fundamental to elucidate organogenesis, it is unlikely that embryonic stem cells will be used for clinical purposes. Postembryonic stage, developing cells are, therefore, the front-runner for regenerative medicine. In addition to autologous cells, both allogeneic and xenogeneic cells are hypothetical candidates to treat specific diseases. This review summarizes the current knowledge on immunological and functional aspects of xeno(allo)-cellular transplantation for cardiomyopathy, diabetes, liver failure, neural diseases, and bone regeneration...
April 2009: Current Opinion in Organ Transplantation
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