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Liver progenitor

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https://www.readbyqxmd.com/read/29691598/hepatocyte-transplantation-and-advancements-in-alternative-cell-sources-for-liver-based-regenerative-medicine
#1
REVIEW
Charlotte A Lee, Siddharth Sinha, Emer Fitzpatrick, Anil Dhawan
Human hepatocyte transplantation has been actively perused as an alternative to liver replacement for acute liver failure and liver-based metabolic defects. Current challenges in this field include a limited cell source, reduced cell viability following cryopreservation and poor engraftment of cells into the recipient liver with consequent limited life span. As a result, alternative stem cell sources such as pluripotent stem cells, fibroblasts, hepatic progenitor cells, amniotic epithelial cells and mesenchymal stem/stromal cells (MSCs) can be used to generate induced hepatocyte like cells (HLC) with each technique exhibiting advantages and disadvantages...
April 24, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29690953/stat3-regulates-liver-progenitor-cell-driven-liver-regeneration-in-zebrafish
#2
Mehwish Khaliq, Sungjin Ko, Yinzi Liu, Hualin Wang, Yonghua Sun, Lila Solnica-Kreze, Donghun Shin
After liver injury, regeneration manifests as either (1) hepatocytes proliferating to restore the lost hepatocyte massor (2) if hepatocyte proliferation is compromised, biliary epithelial cells (BECs) dedifferentiating into liver progenitor cells (LPCs), which subsequently differentiate into hepatocytes. Following pharmacogenetic ablation of hepatocytes in Tg(fabp10a:CFP-NTR) zebrafish, resulting in severe liver injury, signal transducer and activator of transcription 3 (Stat3) and its target gene and negative regulator, socs3a , were upregulated in regenerating livers...
April 24, 2018: Gene Expression
https://www.readbyqxmd.com/read/29686621/pravastatin-protects-against-avascular-necrosis-of-femoral-head-via-autophagy
#3
Yun Liao, Ping Zhang, Bo Yuan, Ling Li, Shisan Bao
Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29679560/developmental-origin-and-morphogenesis-of-the-diaphragm-an-essential-mammalian-muscle
#4
Elizabeth M Sefton, Mirialys Gallardo, Gabrielle Kardon
The diaphragm is a mammalian skeletal muscle essential for respiration and for separating the thoracic and abdominal cavities. Development of the diaphragm requires the coordinated development of muscle, muscle connective tissue, tendon, nerves, and vasculature that derive from different embryonic sources. However, defects in diaphragm development are common and the cause of an often deadly birth defect, Congenital Diaphragmatic Hernia (CDH). Here we comprehensively describe the normal developmental origin and complex spatial-temporal relationship between the different developing tissues to form a functional diaphragm using a developmental series of mouse embryos genetically and immunofluorescently labeled and analyzed in whole mount...
April 18, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29673755/understanding-liver-regeneration-from-mechanisms-to-regenerative-medicine
#5
REVIEW
Hélène Gilgenkrantz, Alexandra Collin de l'Hortet
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities...
April 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29626983/hematopoietic-changes-in-the-offspring-induced-by-maternal-overweight-effect-on-placenta-and-fetal-liver-populations
#6
Luana Leirós, Juliana Barbosa Torreão Dáu, Daphne Pinheiro, Ana Carolina Stumbo Machado, Alessandra Alves Thole, Erika Afonso Costa Cortez, Laís de Carvalho, Simone Nunes de Carvalho
INTRODUCTION: Bone marrow cells (BMC) from obese adult mice display an increased apoptosis rate over proliferation. Hematopoietic stem cells (HSC) form all blood cells and are important BMC used in cell therapy. Because it is known that prenatal development can be affected by adverse metabolic epigenetic programming from the maternal organism, this work aimed to investigate the effects of maternal overweight on placenta and fetal liver hematopoietic niches. METHODS: Overweight was induced in female mice by overfeeding during lactation...
April 2018: Placenta
https://www.readbyqxmd.com/read/29624127/depolarized-hepatocytes-express-the-stem-progenitor-cell-marker-neighbor-of-punc-e11-after-bile-duct-ligation-in-mice
#7
Andrea Bowe, Susanne Zweerink, Vera Mück, Vangelis Kondylis, Sigrid Schulte, Tobias Goeser, Dirk Nierhoff
There is a medical need of biomarkers for disease stratification in cholestatic liver diseases that come along with changes in hepatocyte polarity. Neighbor of Punc E11 (Nope) is an oncofetal marker that is lost after final differentiation and polarization of hepatocytes. We analyzed the expression pattern of Nope and connexin (Cx) 26 as markers of hepatocyte polarization during murine liver development as well as in adult liver with or without bile duct ligation (BDL) by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting (WB), and immunohistochemistry...
April 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29622030/mapping-human-pluripotent-stem-cell-differentiation-pathways-using-high-throughput-single-cell-rna-sequencing
#8
Xiaoping Han, Haide Chen, Daosheng Huang, Huidong Chen, Lijiang Fei, Chen Cheng, He Huang, Guo-Cheng Yuan, Guoji Guo
BACKGROUND: Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. RESULTS: We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells...
April 5, 2018: Genome Biology
https://www.readbyqxmd.com/read/29606873/noninvasive-evaluation-of-the-migration-effect-of-transplanted-endothelial-progenitor-cells-in-ischemic-muscle-using-a-multimodal-imaging-agent
#9
Xingui Peng, Cong Li, Yingying Bai, Xinyi Wang, Yi Zhang, Yanli An, Gao-Jun Teng, Shenghong Ju
Background: Endothelial progenitor cells (EPCs) play an important role in repairing ischemia tissues. However, the survival, migration and therapeutic efficacy of EPCs after transplantation need to be better understood for further cell therapy. Purpose: This study investigated the migration effect of EPCs labeled with a multimodal imaging agent in a murine ischemic hindlimb model, using magnetic resonance imaging (MRI) and optical imaging after transplantation. Methods: EPCs derived from mouse bone marrow were labeled with a multimodal imaging agent and were administered through intracardiac delivery to mice with ischemic hindlimbs...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29606616/direct-conversion-of-mouse-fibroblasts-into-cholangiocyte-progenitor-cells
#10
Kyung Tae Lim, Jonghun Kim, Seon In Hwang, Ludi Zhang, Heonjong Han, Dasom Bae, Kee-Pyo Kim, Yi-Ping Hu, Hans R Schöler, Insuk Lee, Lijian Hui, Dong Wook Han
Disorders of the biliary epithelium, known as cholangiopathies, cause severe and irreversible liver diseases. The limited accessibility of bile duct precludes modeling of several cholangiocyte-mediated diseases. Therefore, novel approaches for obtaining functional cholangiocytes with high purity are needed. Previous work has shown that the combination of Hnf1β and Foxa3 could directly convert mouse fibroblasts into bipotential hepatic stem cell-like cells, termed iHepSCs. However, the efficiency of converting fibroblasts into iHepSCs is low, and these iHepSCs exhibit extremely low differentiation potential into cholangiocytes, thus hindering the translation of iHepSCs to the clinic...
March 29, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29599080/exosomes-from-endothelial-progenitor-cells-improve-the-outcome-of-a-murine-model-of-sepsis
#11
Yue Zhou, Pengfei Li, Andrew J Goodwin, James A Cook, Perry V Halushka, Eugene Chang, Hongkuan Fan
Microvascular dysfunction leads to multi-organ failure and mortality in sepsis. Our previous studies demonstrated that administration of exogenous endothelial progenitor cells (EPCs) confers protection in sepsis as evidenced by reduced vascular leakage, improved organ function, and increased survival. We hypothesize that EPCs protect the microvasculature through the exosomes-mediated transfer of microRNAs (miRNAs). Mice were rendered septic by cecal ligation and puncture (CLP), and EPC exosomes were administered intravenously at 4 hr after CLP...
February 27, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29563755/maturity-of-associating-liver-partition-and-portal-vein-ligation-for-staged-hepatectomy-derived-liver-regeneration-in-a-rat-model
#12
Yi-Fan Tong, Ning Meng, Miao-Qin Chen, Han-Ning Ying, Ming Xu, Billy Lu, Jun-Jie Hong, Yi-Fan Wang, Xiu-Jun Cai
AIM: To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). METHODS: In the present study, ALPPS, partial hepatecotmy (PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified...
March 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29558368/hmgb1-promotes-ductular-reaction-and-tumorigenesis-in-autophagy-deficient-livers
#13
Bilon Khambu, Nazmul Huda, Xiaoyun Chen, Daniel J Antoine, Yong Li, Guoli Dai, Ulrike A Köhler, Wei-Xing Zong, Satoshi Waguri, Sabine Werner, Tim D Oury, Zheng Dong, Xiao-Ming Yin
Autophagy is important for liver homeostasis and the deficiency leads to injury, inflammation, ductular reaction (DR), fibrosis, and tumorigenesis. It is not clear how these events are mechanistically linked to autophagy deficiency. Here we reveal the role of highmobility group box 1 (HMGB1) in two of these processes. First, HMGB1 was required for DR, which represents the expansion of hepatic progenitor cells (HPC) implicated in liver repair and regeneration. DR caused by hepatic toxic diets (DDC or CDE) also depended on HMGB1, indicating that HMGB1 may be generally required for DR in various injury scenarios...
March 20, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29558367/hmgb1-links-chronic-liver-injury-to-progenitor-responses-and-hepatocarcinogenesis
#14
Céline Hernandez, Peter Huebener, Jean-Philippe Pradere, Daniel J Antoine, Richard A Friedman, Robert F Schwabe
Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD...
March 20, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29555660/the-potential-and-challenges-of-alternative-sources-of-%C3%AE-cells-for-the-cure-of-type-1-diabetes
#15
REVIEW
Monia Cito, Silvia Pellegrini, Lorenzo Piemonti, Valeria Sordi
The experience in the field of islet transplantation shows that it is possible to replace β cells in a patient with type 1 diabetes (T1D), but this cell therapy is limited by the scarcity of organ donors and by the danger associated to the immunosuppressive drugs. Stem cell therapy is becoming a concrete opportunity to treat various diseases. In particular, for a disease like T1D, caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure...
March 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29544731/autocrine-transforming-growth-factor-%C3%AE-activin-a-smad-signaling-induces-hepatic-progenitor-cells-undergoing-partial-epithelial-mesenchymal-transition-states
#16
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
https://www.readbyqxmd.com/read/29534881/tumor-promoting-cyanotoxin-microcystin-lr-does-not-induce-procarcinogenic-events-in-adult-human-liver-stem-cells
#17
Jan Raska, Lucie Ctverackova, Aneta Dydowiczova, Iva Sovadinova, Ludek Blaha, Pavel Babica
HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, α-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed...
March 10, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29531353/transdifferentiation-of-pancreatic-progenitor-cells-to-hepatocyte-like-cells-is-not-serum-dependent-when-facilitated-by-extracellular-matrix-proteins
#18
Francis D Gratte, Sara Pasic, John K Olynyk, George C T Yeoh, David Tosh, Deirdre R Coombe, Janina E E Tirnitz-Parker
The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium...
March 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29529390/inhibition-of-gsk-3%C3%AE-induces-ap-1-mediated-osteopontin-expression-to-promote-cholestatic-liver-fibrosis
#19
Shaoyong Zhuang, Xiangwei Hua, Kang He, Tao Zhou, Jiang Zhang, Haoyu Wu, Xiong Ma, Qiang Xia, Jianjun Zhang
The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs. GSK-3β inhibition by SB216763 treatment aggravated liver fibrosis and elevated the expression of osteopontin (OPN) in the BDL mouse model...
March 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29525466/hepatectomy-increases-metastatic-graft-and-growth-in-an-immunocompetent-murine-model-of-peritoneal-metastases
#20
Rea Lo Dico, Annemilai Tijeras-Raballand, Philippe Bonnin, Jean Marie Launay, Rachid Kaci, Cynthia Pimpie, Brice Malgras, Anthony Dohan, Gianluigi Maria Lo Dico, Marc Pocard
BACKGROUND: Curative surgery of synchronous peritoneal metastases (PM) and colorectal liver metastases (LM) has been recently investigated as feasible option. When synchronous peritoneal and liver resection is not achievable, the sequence of the surgery remains unknown. Our hypothesis was that liver resection (LR) promotes peritoneal growth resulting in a non-resectable PM. We sought to analyse the effects of major LR and liver regeneration after hepatectomy in a murine model of PM and the associated angiogenesis...
January 31, 2018: European Journal of Surgical Oncology
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