Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible.

Publication date: Available online 15 October 2019Source: Stem Cell ResearchAuthor(s): Candice Ashmore-Harris, Samuel JI Blackford, Benjamin Grimsdell, Ewelina Kurtys, Marlies C Glatz, Tamir S Rashid, Gilbert O FruhwirthAbstractPrimary hepatocyte transplantation (HTx) is a safe cell therapy for patients with liver disease, but wider application is circumvented by poor cell engraftment due to limitations in hepatocyte quality and transplantation strategies. Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSC) are considered a promising alternative but also require optimisation of transplantation and are often transplanted prior to full maturation. Whole-body in vivo imaging would be highly beneficial to assess engraftment non-invasively and monitor the transplanted cells in the short and long-term.Here we report a lentiviral transduction approach designed to engineer hiPSC-derived HLCs during differentiation. This strategy resulted in the successful production of sodium iodide symporter (NIS)-expressing HLCs that were functionally characterised, transplanted into mice, and subsequently imaged using radionuclide tomography.Graphical Abstract
Source: Stem Cell Research - Category: Stem Cells Source Type: research

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Abstract Liver diseases caused by viral infection, alcohol abuse and metabolic disorders can progress to end-stage liver failure, liver cirrhosis and liver cancer, which are a growing cause of death worldwide. Although liver transplantation and hepatocyte transplantation are useful strategies to promote liver regeneration, they are limited by scarce sources of organs and hepatocytes. Mesenchymal stem cells (MSCs) restore liver injury after hepatogenic differentiation and exert immunomodulatory, anti-inflammatory, antifibrotic, antioxidative stress and antiapoptotic effects on liver cells in vivo. After isolation a...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Authors: Barcelos STA, Dall'Oglio VM, de Araújo A, Cerski CTS, Álvares-da-Silva MR Abstract Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease histologically characterized by edema, necrosis, detachment of endothelial cells in small sinusoidal hepatic and interlobular veins and intrahepatic congestion, which leads to portal hypertension and liver dysfunction. In the Western world, most HSOS cases are associated with myeloablative pretreatment in a hematopoietic stem cell transplantation setting. Here we report a case of a 54 years old female patient, otherwise healthy, with n...
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
Abstract The liver is a major organ responsible for maintaining the body's homeostasis and xenobiotic metabolism. Liver transplantation is essential for the alleviation of many severe liver diseases. However, there are many patients who cannot receive liver transplants because of donor shortage. Therefore development of effective therapeutic drugs that can replace the need for liver transplantation is desired. To this end, model cells that faithfully reproduce hepatic functions are essential. It is expected that human induced pluripotent stem cell (iPS)-derived hepatocyte-like cells, which faithfully reproduce hep...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Kang SH, Kim MY, Eom YW, Baik SK Abstract Mesenchymal stem cell transplantation is an emerging therapy for treating chronic liver diseases. The potential of this treatment has been evaluated in preclinical and clinical studies. Although the mechanisms of mesenchymal stem cell transplantation are still not completely understood, accumulating evidence has revealed that their immunomodulation, differentiation, and antifibrotic properties play a crucial role in liver regeneration. The safety and therapeutic effects of mesenchymal stem cells in patients with chronic liver disease have been observed in many clin...
Source: Gut and Liver - Category: Gastroenterology Tags: Gut Liver Source Type: research
CONCLUSION: The SC-based interventions provide significant improvement in patients with CLD, however, there is a need of randomized, controlled studies with analysis of long-term follow-up. PMID: 31584360 [PubMed - as supplied by publisher]
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
Conclusions. We discuss the many considerations inherent to planning for HSCT preceded by liver transplant in patients with primary immunodeficiencies, including the role of prolonged immunosuppression and the risk of infection before immune reconstitution. We also discuss the implications of potential recipient sensitization against donor stem cells precipitated by exposure of the recipient to the donor lymphocytes from the transplanted organ.
Source: Transplantation - Category: Transplant Surgery Tags: Original Clinical Science–Liver Source Type: research
Authors: Panda PK, Sood R, Kanabar K, Jadon R, Sharma A, Birla S, Mishra P, Kumar T Abstract Dyskeratosis Congenita (DC), a 100-year-old known rare hereditary entity, has recently changed its definition as per the pathogenetic model in the last decade. Now it is well known as one of the telomeropathies, pathognomonically characterized by a triad of reticulate pigmentation of the skin, nail dystrophy, and mucosal leukoplakia. It is a progressive systemic disorder which usually presents with involvement of several family members. Malignancies are increasingly reported. Clinical diagnosis is simple once there is a sus...
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
Publication date: Available online 12 September 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Ja Sung Choi, Dong-Sik Chae, Hyun Aae Ryu, Sung-Whan KimAbstractAlthough human adipose tissue-derived stromal vascular fraction (SVF) has been considered a promising source of stem cells, its characteristics relevant to treatment of a damaged liver have not been fully elucidated. In the present study, we sought to characterize the property of human SVF and determine the therapeutic utility of SVF in the liver cirrhosis model. We performed microarray, quantitative (q)-PCR experimen...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research
In this study, canine adipose-derived mesenchymal stem cells (cADSCs) therapeutic potential was investigated in artificially induced acute liver injury model by CCl4 in canines. The primary cADSCs cells were cultured and then intravenously administered into the canine animal model. Six cross-breed dogs were divided into three groups including blank control group, CCl4 model group, CCl4 induced cADSCs transplantation group.The results showed that after intraperitoneal injection of CCl4 solution, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Albumin (ALB) in peripheral blood of experiment...
Source: Research in Veterinary Science - Category: Veterinary Research Source Type: research
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