Agonist c-Met Monoclonal Antibody Augments the Proliferation of hiPSC-derived Hepatocyte-Like Cells and Improves Cell Transplantation Therapy for Liver Failure in Mice.

Abstract:

:Rationale: Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSCs) have been developed to address the shortage of primary human hepatocytes (PHHs) for therapeutic applications. However, the in vivo repopulation capacity of HLCs remains limited. This study investigated the roles of agonist antibody activating the c-Met receptor in promoting the in vivo proliferation and repopulation of engrafted PHHs and/or HLCs in mice with liver injuries due to different causes. Methods: An agonist c-Met receptor antibody (5D5) was used to treat PHHs and hiPSC-HLCs in both cell culture and hepatocyte-engrafted immunodeficient mice mimicking various inherited and acquired liver diseases. The promoting roles and potential influence on the hepatic phenotype of the 5D5 regimen in cell transplantation-based therapeutic applications were systematically evaluated. Results: In hiPSC-HLC cell cultures, 5D5 treatment significantly stimulated c-Met receptor downstream signalling pathways and accelerated cell proliferation in dose-dependent and reversible manners. In contrast, only slight but nonsignificant promotion was observed in 5D5-treated PHHs. In vivo administration of 5D5 greatly promoted the expansion of implanted hiPSC-HLCs in fumarylacetoacetate hydrolase (Fah) deficient mice, resulting in significantly increased human albumin levels and high human liver chimerism (over 40%) in the transplanted mice at week 8 after transplantation. More importantly, transplantation of hiPSC-HLCs in combination with 5D5 significantly prolonged animal survival and ameliorated liver pathological changes in mice with acute and/or chronic liver injuries caused by Fas agonistic antibody treatment, carbon tetrachloride treatment and/or tyrosinemic stress. Conclusion: Our results demonstrated that the proliferation of hiPSC-HLCs can be enhanced by antibody-mediated modulation of c-Met signalling and facilitate hiPSC-HLC-based therapeutic applications for life-threatening liver diseases.

journal_name

Theranostics

journal_title

Theranostics

authors

Yuan L,Zhang Y,Liu X,Chen Y,Zhang L,Cao J,Li X,Wang M,Wu K,Zhang J,Liu G,Tang Q,Yuan Q,Cheng T,Xia N

doi

10.7150/thno.30009

subject

Has Abstract

pub_date

2019-04-06 00:00:00

pages

2115-2128

issue

7

issn

1838-7640

pii

thnov09p2115

journal_volume

9

pub_type

杂志文章
  • Lung Cancer-Targeting Peptides with Multi-subtype Indication for Combinational Drug Delivery and Molecular Imaging.

    abstract::Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.17573

    authors: Chi YH,Hsiao JK,Lin MH,Chang C,Lan CH,Wu HC

    更新日期:2017-04-10 00:00:00

  • PI3K/AKT inhibition reverses R-CHOP resistance by destabilizing SOX2 in diffuse large B cell lymphoma.

    abstract::Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen, while the remaining therapeutic options are limited. Thus, understanding the underlying mechanisms and developing therapeutic approaches are urgently needed. Methods: We generated two germinal center B ce...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.41362

    authors: Chen J,Ge X,Zhang W,Ding P,Du Y,Wang Q,Li L,Fang L,Sun Y,Zhang P,Zhou Y,Zhang L,Lv X,Li L,Zhang X,Zhang Q,Xue K,Gu H,Lei Q,Wong J,Hu W

    更新日期:2020-02-10 00:00:00

  • Histone H3K27 methyltransferase EZH2 and demethylase JMJD3 regulate hepatic stellate cells activation and liver fibrosis.

    abstract::Rationale: As the central hallmark of liver fibrosis, transdifferentiation of hepatic stellate cells (HSCs), the predominant contributor to fibrogenic hepatic myofibroblast responsible for extracellular matrix (ECM) deposition, is characterized with transcriptional and epigenetic remodeling. We aimed to characterize t...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.46360

    authors: Jiang Y,Xiang C,Zhong F,Zhang Y,Wang L,Zhao Y,Wang J,Ding C,Jin L,He F,Wang H

    更新日期:2021-01-01 00:00:00

  • A Comprehensive Study of Vesicular and Non-Vesicular miRNAs from a Volume of Cerebrospinal Fluid Compatible with Clinical Practice.

    abstract::Cerebrospinal fluid (CSF) microRNAs (miRNAs) have emerged as potential biomarkers for minimally invasive diagnosis of central nervous system malignancies. However, despite significant advances in recent years, this field still suffers from poor data reproducibility. This is especially true in cases of infants, conside...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.31502

    authors: Prieto-Fernández E,Aransay AM,Royo F,González E,Lozano JJ,Santos-Zorrozua B,Macias-Camara N,González M,Garay RP,Benito J,Garcia-Orad A,Falcón-Pérez JM

    更新日期:2019-06-19 00:00:00

  • The Circadian Clock Gene Bmal1 Controls Intestinal Exporter MRP2 and Drug Disposition.

    abstract::The intestinal exporter MRP2 plays an important role in disposition and elimination of a wide range of drugs. Here, we aimed to clarify the impact of circadian clock on intestinal MRP2, and to determine the molecular mechanisms for generation of diurnal MRP2 expression. Methods: The regulatory effects of Bmal1 on inte...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.33395

    authors: Yu F,Zhang T,Zhou C,Xu H,Guo L,Chen M,Wu B

    更新日期:2019-04-13 00:00:00

  • Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer.

    abstract::Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAFV600E mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.17322

    authors: Wei WJ,Sun ZK,Shen CT,Song HJ,Zhang XY,Qiu ZL,Luo QY

    更新日期:2017-02-23 00:00:00

  • Copy Number Amplification of DNA Damage Repair Pathways Potentiates Therapeutic Resistance in Cancer.

    abstract::Rationale: Loss of DNA damage repair (DDR) in the tumor is an established hallmark of sensitivity to DNA damaging agents such as chemotherapy. However, there has been scant investigation into gain-of-function alterations of DDR genes in cancer. This study aims to investigate to what extent copy number amplification of...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.39341

    authors: Wu Z,Li S,Tang X,Wang Y,Guo W,Cao G,Chen K,Zhang M,Guan M,Yang D

    更新日期:2020-03-04 00:00:00

  • Adaptive changes induced by noble-metal nanostructures in vitro and in vivo.

    abstract::The unique features of noble-metal nanostructures (NMNs) are leading to unprecedented expansion of research and exploration of their application in therapeutics, diagnostics and bioimaging fields. With the ever-growing applications of NMNs, both therapeutic and environmental NMNs are likely to be exposed to tissues an...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.42569

    authors: Huang Q,Zhang J,Zhang Y,Timashev P,Ma X,Liang XJ

    更新日期:2020-04-27 00:00:00

  • Real time dynamic imaging and current targeted therapies in the war on cancer: a new paradigm.

    abstract::In biology, as every science student is made to learn, ontology recapitulates phylogeny. In medicine, however, oncology recapitulates polemology, the science of warfare: The medical establishment is transitioning from highly toxic poisons that kill rapidly dividing normal and malignant cells with little specificity to...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.5658

    authors: Paulmurugan R,Oronsky B,Brouse CF,Reid T,Knox S,Scicinski J

    更新日期:2013-05-25 00:00:00

  • Neurogliovascular dysfunction in a model of repeated traumatic brain injury.

    abstract::Traumatic brain injury (TBI) research has focused on moderate to severe injuries as their outcomes are significantly worse than those of a mild TBI (mTBI). However, recent epidemiological evidence has indicated that a series of even mild TBIs greatly increases the risk of neurodegenerative and psychiatric disorders. N...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.24747

    authors: Adams C,Bazzigaluppi P,Beckett TL,Bishay J,Weisspapir I,Dorr A,Mester JR,Steinman J,Hirschler L,Warnking JM,Barbier EL,McLaurin J,Sled JG,Stefanovic B

    更新日期:2018-09-09 00:00:00

  • Introducing Theranostics Journal - From the Editor-in-Chief.

    abstract::Theranostics is a multidisciplinary journal that publishes innovative and original research papers reflecting the field of molecular imaging, molecular therapeutics, multifunctional nanoparticle platforms, image-guided therapy, and translational nanomedicine. A broad spectrum of biomedical research that can be applied...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno/v01p0001

    authors: Chen XS

    更新日期:2011-01-08 00:00:00

  • Theranostic potential of oncolytic vaccinia virus.

    abstract::Biological cancer therapies, such as oncolytic, or replication-selective viruses have advantages over traditional therapeutics as they can employ multiple different mechanisms to target and destroy cancers (including direct cell lysis, immune activation and vascular collapse). This has led to their rapid recent clinic...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.3724

    authors: Rojas JJ,Thorne SH

    更新日期:2012-01-01 00:00:00

  • Detection of high-risk atherosclerotic plaques with ultrasound molecular imaging of glycoprotein IIb/IIIa receptor on activated platelets.

    abstract:OBJECTIVE:Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated plat...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.10020

    authors: Guo S,Shen S,Wang J,Wang H,Li M,Liu Y,Hou F,Liao Y,Bin J

    更新日期:2015-02-05 00:00:00

  • Dual-Channel Fluorescence Imaging of Hydrogel Degradation and Tissue Regeneration in the Brain.

    abstract::The ability of brain tissue to regenerate is limited; therefore, brain diseases (i.e., trauma, stroke, tumors) often lead to irreversible motor and cognitive impairments. Therapeutic interventions using various types of injectable biomaterials have been investigated to promote endogenous neural differentiation. Despit...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35606

    authors: Park GK,Kim SH,Kim K,Das P,Kim BG,Kashiwagi S,Choi HS,Hwang NS

    更新日期:2019-05-31 00:00:00

  • Discovery of extracellular vesicles derived miR-181a-5p in patient's serum as an indicator for bone-metastatic prostate cancer.

    abstract::Purpose: To identify extracellular vesicle (EV)-delivered microRNAs in the patient's serum as indicators for bone-metastatic prostate cancer. Methods: First, the profiling change of serum EV-delivered miRNAs in patients with either benign prostatic hyperplasia (BPH), non-bone metastatic prostate cancer or bone-metasta...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.49186

    authors: Wang Y,Fang YX,Dong B,Du X,Wang J,Wang X,Gao WQ,Xue W

    更新日期:2021-01-01 00:00:00

  • Erratum: pH-Sensitive Nano-Complexes Overcome Drug Resistance and Inhibit Metastasis of Breast Cancer by Silencing Akt Expression: Erratum.

    abstract::[This corrects the article DOI: 10.7150/thno.21516.]. ...

    journal_title:Theranostics

    pub_type: 已发布勘误

    doi:10.7150/thno.42847

    authors: Yin J,Lang T,Cun D,Zheng Z,Huang Y,Yin Q,Yu H,Li Y

    更新日期:2020-01-18 00:00:00

  • Recommendations for reporting on emerging optical imaging agents to promote clinical approval.

    abstract::Intraoperative fluorescence imaging is particularly well-suited for surgical applications due to its inherently high sensitivity, resolution, and ability to provide images in real-time. To date, the intraoperative observation of fluorescence has largely been subjective. With the need to show objective evidence in orde...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.27384

    authors: Tummers WS,Warram JM,van den Berg NS,Miller SE,Swijnenburg RJ,Vahrmeijer AL,Rosenthal EL

    更新日期:2018-10-22 00:00:00

  • Nanoscale microenvironment engineering based on layer-by-layer self-assembly to regulate hair follicle stem cell fate for regenerative medicine.

    abstract::Hair regenerative medicine, a promising strategy for the treatment of hair loss, will likely involve the transplantation of autologous hair follicular stem cells (HFSCs) and dermal papilla cells (DPCs) into regions of hair loss. Cyclic hair regeneration results from the periodic partial activation of HFSCs. However, p...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.48723

    authors: Chen P,Miao Y,Zhang F,Huang J,Chen Y,Fan Z,Yang L,Wang J,Hu Z

    更新日期:2020-09-22 00:00:00

  • pH responsive superporogen combined with PDT based on poly Ce6 ionic liquid grafted on SiO2 for combating MRSA biofilm infection.

    abstract::Background: Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. M...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.42922

    authors: Wang C,Chen P,Qiao Y,Kang Y,Yan C,Yu Z,Wang J,He X,Wu H

    更新日期:2020-03-26 00:00:00

  • A new class of PentixaFor- and PentixaTher-based theranostic agents with enhanced CXCR4-targeting efficiency.

    abstract::Non-invasive PET imaging of CXCR4 expression in cancer and inflammation as well as CXCR4-targeted radioligand therapy (RLT) have recently found their way into clinical research by the development of the theranostic agents [68Ga]PentixaFor (cyclo(D-Tyr1-D-[NMe]Orn2(AMBS-[68Ga]DOTA)-Arg3-Nal4-Gly5) = [68Ga]DOTA-AMBS-CPC...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.45537

    authors: Osl T,Schmidt A,Schwaiger M,Schottelius M,Wester HJ

    更新日期:2020-07-09 00:00:00

  • Involvement of reactive oxygen species in sonodynamically induced apoptosis using a novel porphyrin derivative.

    abstract::In this study, we investigated the induction of apoptosis by ultrasound in the presence of the novel porphyrin derivative DCPH-P-Na(I). HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of DCPH-P-Na(I), and the induction of apoptosis was examined by analyzing cell morphology, DNA fragm...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.3899

    authors: Yumita N,Iwase Y,Nishi K,Komatsu H,Takeda K,Onodera K,Fukai T,Ikeda T,Umemura S,Okudaira K,Momose Y

    更新日期:2012-01-01 00:00:00

  • Role of Extracellular Vesicles in Viral and Bacterial Infections: Pathogenesis, Diagnostics, and Therapeutics.

    abstract::Extracellular vesicles (EVs), or exosomes, are nanovesicles of endocytic origin that carry host and pathogen-derived protein, nucleic acid, and lipid cargos. They are secreted by most cell types and play important roles in normal cell-to-cell communications but can also spread pathogen- and host-derived molecules duri...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.20576

    authors: Rodrigues M,Fan J,Lyon C,Wan M,Hu Y

    更新日期:2018-04-09 00:00:00

  • Cancer immunotherapy is accompanied by distinct metabolic patterns in primary and secondary lymphoid organs observed by non-invasive in vivo 18F-FDG-PET.

    abstract::Purpose: Cancer immunotherapy depends on a systemic immune response, but the basic underlying mechanisms are still largely unknown. Despite the very successful and widespread use of checkpoint inhibitors in the clinic, the majority of cancer patients do not benefit from this type of treatment. In this translational st...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35989

    authors: Schwenck J,Schörg B,Fiz F,Sonanini D,Forschner A,Eigentler T,Weide B,Martella M,Gonzalez-Menendez I,Campi C,Sambuceti G,Seith F,Quintanilla-Martinez L,Garbe C,Pfannenberg C,Röcken M,la Fougere C,Pichler BJ,Kneilling M

    更新日期:2020-01-01 00:00:00

  • Type H blood vessels in bone modeling and remodeling.

    abstract::In the mammalian skeletal system, osteogenesis and angiogenesis are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling. Recent studies have expanded our knowledge about the molecular and cellular mechanisms responsible for coupling angiogenesis and bon...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.34126

    authors: Peng Y,Wu S,Li Y,Crane JL

    更新日期:2020-01-01 00:00:00

  • Antibody affinity and valency impact brain uptake of transferrin receptor-targeted gold nanoparticles.

    abstract::Rationale: The ability to treat invalidating neurological diseases is impeded by the presence of the blood-brain barrier (BBB), which inhibits the transport of most blood-borne substances into the brain parenchyma. Targeting the transferrin receptor (TfR) on the surface of brain capillaries has been a popular strategy...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.25228

    authors: Johnsen KB,Bak M,Kempen PJ,Melander F,Burkhart A,Thomsen MS,Nielsen MS,Moos T,Andresen TL

    更新日期:2018-05-24 00:00:00

  • YTHDF1-enhanced iron metabolism depends on TFRC m6A methylation.

    abstract::Background: Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-met...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.51231

    authors: Ye J,Wang Z,Chen X,Jiang X,Dong Z,Hu S,Li W,Liu Y,Liao B,Han W,Shen J,Xiao M

    更新日期:2020-10-26 00:00:00

  • Smart Sorting of Tumor Phenotype with Versatile Fluorescent Ag Nanoclusters by Sensing Specific Reactive Oxygen Species.

    abstract::Reactive oxygen species (ROS) play a crucial role in cancer formation and development, especially cancer metastasis. However, lack of a precise tool, which could accurately distinguish specific types of ROS, restricts an in-depth study of ROS in cancer development and progression. Herein, we designed smart and versati...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.38422

    authors: Chen X,Wang T,Le W,Huang X,Gao M,Chen Q,Xu S,Yin D,Fu Q,Shao C,Chen B,Shi D

    更新日期:2020-02-10 00:00:00

  • Downregulation of SIRT7 by 5-fluorouracil induces radiosensitivity in human colorectal cancer.

    abstract::5-Fluorouracil (5-FU) combined with radiotherapy is a common treatment strategy to treat human cancers, but the underlying mechanisms of this combination treatment remain unclear. Here, we report that NAD+-dependent deacetylase sirtuin-7 (SIRT7) protein levels were decreased due to 5-FU exposure rendering colorectal c...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.18804

    authors: Tang M,Lu X,Zhang C,Du C,Cao L,Hou T,Li Z,Tu B,Cao Z,Li Y,Chen Y,Jiang L,Wang H,Wang L,Liu B,Xu X,Luo J,Wang J,Gu J,Wang H,Zhu WG

    更新日期:2017-03-22 00:00:00

  • A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine.

    abstract::Rationale: Within the field of personalized medicine there is an increasing focus on designing flexible, multifunctional drug delivery systems that combine high efficacy with minimal side effects, by tailoring treatment to the individual. Methods: We synthesized a chemically stabilized ~4 nm nucleic acid nanoscaffold,...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.32060

    authors: Andersen VL,Vinther M,Kumar R,Ries A,Wengel J,Nielsen JS,Kjems J

    更新日期:2019-04-13 00:00:00

  • CD146-targeted immunoPET and NIRF Imaging of Hepatocellular Carcinoma with a Dual-Labeled Monoclonal Antibody.

    abstract::Overexpression of CD146 has been correlated with aggressiveness, recurrence rate, and poor overall survival in hepatocellular carcinoma (HCC) patients. In this study, we set out to develop a CD146-targeting probe for high-contrast noninvasive in vivo positron emission tomography (PET) and near-infrared fluorescence (N...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.15568

    authors: Hernandez R,Sun H,England CG,Valdovinos HF,Ehlerding EB,Barnhart TE,Yang Y,Cai W

    更新日期:2016-08-08 00:00:00