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Open AccessArticle

Depletion of Bone Marrow-Derived Fibrocytes Attenuates TAA-Induced Liver Fibrosis in Mice

1
Department of Gastroenterology, Justus Liebig University, D-35392 Giessen, Germany
2
Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), D-61231 Bad Nauheim, Germany
3
Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University, D-35392 Giessen, Germany
4
Department of Internal Medicine, Bürgerhospital, D-61169 Friedberg, Germany
5
Department of Internal Medicine, Hochwaldkrankenhaus, D-61231 Bad Nauheim, Germany
6
Institute of Veterinary Pathology, Justus Liebig University, D-35392 Giessen, Germany
7
Institute of Medical Informatics, Justus Liebig University, D-35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Cells 2019, 8(10), 1210; https://doi.org/10.3390/cells8101210
Received: 20 September 2019 / Accepted: 5 October 2019 / Published: 7 October 2019
Bone marrow-derived fibrocytes (FC) represent a unique cell type, sharing features of both mesenchymal and hematopoietic cells. FC were shown to specifically infiltrate the injured liver and participate in fibrogenesis. Moreover, FC exert a variety of paracrine functions, thus possibly influencing the disease progression. However, the overall contribution of FC to liver fibrosis remains unclear. We aimed to study the effect of a specific FC depletion, utilizing a herpes simplex virus thymidine kinase (HSV-TK)/Valganciclovir suicide gene strategy. Fibrosis was induced by oral thioacetamide (TAA) administration in C57BL/6J mice. Hepatic hydroxyproline content was assessed for the primary readout. The HSV-TK model enabled the specific depletion of fibrocytes. Hepatic hydroxyproline content was significantly reduced as a result of the fibrocyte ablation (−7.8%; 95% CI: 0.7–14.8%; p = 0.033), denoting a reduced deposition of fibrillar collagens. Lower serum alanine transaminase levels (−20.9%; 95% CI: 0.4–36.9%; p = 0.049) indicate a mitigation of liver-specific cellular damage. A detailed mode of action, however, remains yet to be identified. The present study demonstrates a relevant functional contribution of fibrocytes to chronic toxic liver fibrosis, contradicting recent reports. Our results emphasize the need to thoroughly study the biology of fibrocytes in order to understand their importance for hepatic fibrogenesis. View Full-Text
Keywords: fibrocytes; liver fibrosis; bone marrow; myofibroblasts; thioacetamide (TAA); HSV-TK fibrocytes; liver fibrosis; bone marrow; myofibroblasts; thioacetamide (TAA); HSV-TK
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Hempel, F.; Roderfeld, M.; Savai, R.; Sydykov, A.; Irungbam, K.; Schermuly, R.; Voswinckel, R.; Köhler, K.; Churin, Y.; Kiss, L.; Bier, J.; Pons-Kühnemann, J.; Roeb, E. Depletion of Bone Marrow-Derived Fibrocytes Attenuates TAA-Induced Liver Fibrosis in Mice. Cells 2019, 8, 1210.

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