In Vitro Generated Equine Hepatic-Like Progenitor Cells as a Novel Potent Cell Pool for Equine Metabolic Syndrome (EMS) Treatment.
Abstract: Equine metabolic syndrome (EMS) is recognized as one of the leading cause of health threatening in veterinary medicine worldwide. Recently, PTP1B inhibition has been proposed as an interesting strategy for liver insulin resistance reversion in both equines and humans, however as being a multifactorial disease, proper management of EMS horses further necessities additional interventional approaches aiming at repairing and restoring liver functions. In this study, we hypothesized that in vitro induction of Eq_ASCs hepatogenic differentiation will generate a specialized liver progenitor-like cell population exhibiting similar phenotypic characteristics and regenerative potential as native hepatic progenitor cells. Our obtained data demonstrated that Eq_ASCs-derived liver progenitor cells (Eq_HPCs) displayed typical flattened polygonal morphology with packed fragmented mitochondrial net, lowered mesenchymal CD105 and CD90 surface markers expression, and significant high expression levels of specific hepatic lineage genes including PECAM-1, ALB, AFP and HNF4A. therewith, generated Eq_HPCs exhibited potentiated stemness and pluripotency markers expression (NANOG, SOX-2 and OCT-4). Hence, in vitro generation of hepatic progenitor-like cells retaining high differentiation capacity represents a promising new approach for the establishment of cell-based targeted therapies for the restoration of proper liver functions in EMS affected horses.
© 2023. The Author(s).
Publication Date: 2023-01-20 PubMed ID: 36658383PubMed Central: PMC10185601DOI: 10.1007/s12015-023-10507-3Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the use of lab-grown liver cells from horses to treat equine metabolic syndrome (EMS), a common disease that affects the liver function of horses. This approach involves stimulating specific cells to transform into liver-like cells and target liver regeneration, which could provide new strategies for treatment.
Objective and Hypothesis
- The researchers were aiming to find novel ways to manage equine metabolic syndrome (EMS), a common condition in horses that poses a serious health risk.
- The hypothesized method involved stimulating equine adipose-derived stem cells (Eq_ASCs) in the lab to differentiate into liver progenitor-like cells, which would have similar features and regeneration capabilities as natural liver cells.
Methods and Experimental Approach
- The Eq_ASCs were induced to differentiate into liver progenitor cells (Eq_HPCs).
- The researchers closely observed these Eq_HPCs, examining their shape, the expression of mesenchymal markers (CD105 and CD90), and their mitochondrial structure to ensure they aligned with naturally occurring liver cells.
Findings and Results
- The data revealed that the artificially generated liver cells demonstrated typical traits of actual liver cells, such as specific flattened polygonal shape and packed fragmented mitochondrial structure.
- The cells presented low expression levels of mesenchymal markers, which are certain proteins usually expressed on the cell surface, aligning them with the typical appearance of liver cells.
- They also exhibited high expression levels of genes specific to liver lineage—PECAM-1, ALB, AFP and HNF4A.
- These cells showed potentiated expression of markers related to stemness and pluripotency (NANOG, SOX-2, and OCT-4), indicating a high potential for differentiation.
Conclusion and Implications
- The findings suggest that artificially generating hepatic progenitor-like cells with a high differentiation capacity is a promising approach for future EMS treatments.
- This presents potential opportunities for cell-based targeted therapies aimed at restoring liver function in horses affected by EMS.
Cite This Article
APA
Marycz K, Bourebaba N, Serwotka-Suszczak A, Mularczyk M, Galuppo L, Bourebaba L.
(2023).
In Vitro Generated Equine Hepatic-Like Progenitor Cells as a Novel Potent Cell Pool for Equine Metabolic Syndrome (EMS) Treatment.
Stem Cell Rev Rep, 19(4), 1124-1134.
https://doi.org/10.1007/s12015-023-10507-3 Publication
Researcher Affiliations
- International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114, Wisznia Mau0142a, Poland. kmmarycz@ucdavis.edu.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, 95516, USA. kmmarycz@ucdavis.edu.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocu0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocu0142aw, Poland.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocu0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocu0142aw, Poland.
- International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114, Wisznia Mau0142a, Poland.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocu0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocu0142aw, Poland.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, 95516, USA.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocu0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocu0142aw, Poland. lynda.bourebaba@upwr.edu.pl.
MeSH Terms
- Humans
- Horses
- Animals
- Metabolic Syndrome / therapy
- Metabolic Syndrome / metabolism
- Mesenchymal Stem Cells
- Stem Cells / metabolism
- Insulin Resistance
- Liver / metabolism
Conflict of Interest Statement
Not applicable.
References
This article includes 47 references
- Frank N, Geor RJ, Bailey SR, Durham AE, Johnson PJ. Equine metabolic syndrome.. J Vet Intern Med 2010 May-Jun;24(3):467-75.
- Carslake HB, Pinchbeck GL, McGowan CM. Equine metabolic syndrome in UK native ponies and cobs is highly prevalent with modifiable risk factors.. Equine Vet J 2021 Sep;53(5):923-934.
- Gehlen H, Schwarz B, Bartmann C, Gernhardt J, Stu00f6ckle SD. Pituitary Pars Intermedia Dysfunction and Metabolic Syndrome in Donkeys.. Animals (Basel) 2020 Dec 8;10(12).
- Thiemann AK, Buil J, Rickards K, Sullivan RJ. A review of laminitis in the donkey. Equine Veterinary Education. 2022;34(10):553u2013560. doi: 10.1111/eve.13533.
- Karikoski NP, Horn I, McGowan TW, McGowan CM. The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital.. Domest Anim Endocrinol 2011 Oct;41(3):111-7.
- Frank N. Equine metabolic syndrome.. Vet Clin North Am Equine Pract 2011 Apr;27(1):73-92.
- Dewidar B, Kahl S, Pafili K, Roden M. Metabolic liver disease in diabetes - From mechanisms to clinical trials.. Metabolism 2020 Oct;111S:154299.
- Geervliet E, Bansal R. Matrix Metalloproteinases as Potential Biomarkers and Therapeutic Targets in Liver Diseases.. Cells 2020 May 13;9(5).
- Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells.. J Clin Invest 2002 May;109(10):1291-302.
- Pan J, Zhou L, Zhang C, Xu Q, Sun Y. Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.. Signal Transduct Target Ther 2022 Jun 4;7(1):177.
- Rao MN, Shinnar AE, Noecker LA, Chao TL, Feibush B, Snyder B, Sharkansky I, Sarkahian A, Zhang X, Jones SR, Kinney WA, Zasloff M. Aminosterols from the dogfish shark Squalus acanthias.. J Nat Prod 2000 May;63(5):631-5.
- Lantz KA, Hart SG, Planey SL, Roitman MF, Ruiz-White IA, Wolfe HR, McLane MP. Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice.. Obesity (Silver Spring) 2010 Aug;18(8):1516-23.
- Krishnan N, Koveal D, Miller DH, Xue B, Akshinthala SD, Kragelj J, Jensen MR, Gauss CM, Page R, Blackledge M, Muthuswamy SK, Peti W, Tonks NK. Targeting the disordered C terminus of PTP1B with an allosteric inhibitor.. Nat Chem Biol 2014 Jul;10(7):558-66.
- Bourebaba L, u0141yczko J, Alicka M, Bourebaba N, Szumny A, Fal AM, Marycz K. Inhibition of Protein-tyrosine Phosphatase PTP1B and LMPTP Promotes Palmitate/Oleate-challenged HepG2 Cell Survival by Reducing Lipoapoptosis, Improving Mitochondrial Dynamics and Mitigating Oxidative and Endoplasmic Reticulum Stress.. J Clin Med 2020 May 1;9(5).
- Alicka M, Kornicka-Garbowska K, Roecken M, Marycz K. Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity-Short Communication.. Int J Mol Sci 2019 Nov 22;20(23).
- Shamsuddin SA, Chan AML, Ng MH, Yazid MD, Law JX, Hj Idrus RB, Fauzi MB, Mohd Yunus MH, Lokanathan Y. Stem cells as a potential therapy in managing various disorders of metabolic syndrome: a systematic review.. Am J Transl Res 2021;13(11):12217-12227.
- Enns GM, Millan MT. Cell-based therapies for metabolic liver disease.. Mol Genet Metab 2008 Sep-Oct;95(1-2):3-10.
- So J, Kim A, Lee SH, Shin D. Liver progenitor cell-driven liver regeneration.. Exp Mol Med 2020 Aug;52(8):1230-1238.
- Tang C, Chen H, Jiang L, Liu L. Liver Regeneration: Changes in Oxidative Stress, Immune System, Cytokines, and Epigenetic Modifications Associated with Aging.. Oxid Med Cell Longev 2022;2022:9018811.
- Marycz K, Grzesiak J, Wrzeszcz K, Golonka P. Adipose stem cell combined with plasma-based implant bone tissue differentiation in vitro and in a horse with a phalanx digitalis distalis fracture: a case report. Veterinu00e1rnu00ed Medicu00edna. 2012;57(11):610u2013617. doi: 10.17221/6469-VETMED.
- Talu00e9ns-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gu00f3mez-Lechu00f3n MJ. Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells.. World J Gastroenterol 2006 Sep 28;12(36):5834-45.
- Fan Y, Abrahamsen G, McGrath JJ, Mackay-Sim A. Altered cell cycle dynamics in schizophrenia.. Biol Psychiatry 2012 Jan 15;71(2):129-35.
- Martinotti, S., & Ranzato, E. (2019). Scratch wound healing assay. In K. Turksen (Ed.), Epidermal cells (Vol. 2109, pp. 225u2013229). Springer US. 10.1007/7651_2019_259
- Bognar Z, Fekete K, Bognar R, Szabo A, Vass RA, Sumegi B. Amiodarone's major metabolite, desethylamiodarone, induces apoptosis in human cervical cancer cells.. Can J Physiol Pharmacol 2018 Oct;96(10):1004-1011.
- Bourebaba L, Kornicka-Garbowska K, Al Naem M, Ru00f6cken M, u0141yczko J, Marycz K. MSI-1436 improves EMS adipose derived progenitor stem cells in the course of adipogenic differentiation through modulation of ER stress, apoptosis, and oxidative stress.. Stem Cell Res Ther 2021 Feb 3;12(1):97.
- Mularczyk M, Bourebaba N, Marycz K, Bourebaba L. Astaxanthin Carotenoid Modulates Oxidative Stress in Adipose-Derived Stromal Cells Isolated from Equine Metabolic Syndrome Affected Horses by Targeting Mitochondrial Biogenesis.. Biomolecules 2022 Jul 27;12(8).
- Cunningham RA, Holland M, McWilliams E, Hodi FS, Severgnini M. Detection of clinically relevant immune checkpoint markers by multicolor flow cytometry.. J Biol Methods 2019;6(2):e114.
- Bourebaba L, Michalak I, Baouche M, Kucharczyk K, Marycz K. Cladophora glomerata methanolic extract promotes chondrogenic gene expression and cartilage phenotype differentiation in equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome.. Stem Cell Res Ther 2019 Dec 17;10(1):392.
- Weiss C, Kornicka-Grabowska K, Mularczyk M, Siwinska N, Marycz K. Extracellular Microvesicles (MV's) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells.. Stem Cell Rev Rep 2020 Dec;16(6):1343-1355.
- Peng Q, Alipour H, Porsborg S, Fink T, Zachar V. Evolution of ASC Immunophenotypical Subsets During Expansion In Vitro.. Int J Mol Sci 2020 Feb 19;21(4).
- Zhao D, Chen S, Cai J, Guo Y, Song Z, Che J, Liu C, Wu C, Ding M, Deng H. Derivation and characterization of hepatic progenitor cells from human embryonic stem cells.. PLoS One 2009 Jul 31;4(7):e6468.
- Das S, Hajnu00f3czky N, Antony AN, Csordu00e1s G, Gaspers LD, Clemens DL, Hoek JB, Hajnu00f3czky G. Mitochondrial morphology and dynamics in hepatocytes from normal and ethanol-fed rats.. Pflugers Arch 2012 Jul;464(1):101-9.
- Kornicka-Garbowska K, Galuppo L, Marycz K. At the Dawn of Polytherapy for Laminitis Treatment- Novel Approach to an the Old Problems.. Stem Cell Rev Rep 2021 Oct;17(5):1926-1927.
- Furuya K, Zheng YW, Sako D, Iwasaki K, Zheng DX, Ge JY, Liu LP, Furuta T, Akimoto K, Yagi H, Hamada H, Isoda H, Oda T, Ohkohchi N. Enhanced hepatic differentiation in the subpopulation of human amniotic stem cells under 3D multicellular microenvironment.. World J Stem Cells 2019 Sep 26;11(9):705-721.
- Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, Kato T, Okochi H, Ochiya T. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure.. J Gastroenterol Hepatol 2009 Jan;24(1):70-7.
- Ruiz JC, Ludlow JW, Sherwood S, Yu G, Wu X, Gimble JM. Differentiated human adipose-derived stem cells exhibit hepatogenic capability in vitro and in vivo.. J Cell Physiol 2010 Nov;225(2):429-36.
- Ghaedi M, Tuleuova N, Zern MA, Wu J, Revzin A. Bottom-up signaling from HGF-containing surfaces promotes hepatic differentiation of mesenchymal stem cells.. Biochem Biophys Res Commun 2011 Apr 8;407(2):295-300.
- Choi J, Kang S, Kim B, So S, Han J, Kim GN, Lee MY, Roh S, Lee JY, Oh SJ, Sung YH, Lee Y, Kim SH, Kang E. Efficient hepatic differentiation and regeneration potential under xeno-free conditions using mass-producible amnion-derived mesenchymal stem cells.. Stem Cell Res Ther 2021 Nov 12;12(1):569.
- Das S, Hajnu00f3czky N, Antony AN, Csordu00e1s G, Gaspers LD, Clemens DL, Hoek JB, Hajnu00f3czky G. Mitochondrial morphology and dynamics in hepatocytes from normal and ethanol-fed rats.. Pflugers Arch 2012 Jul;464(1):101-9.
- Du C, Feng Y, Qiu D, Xu Y, Pang M, Cai N, Xiang AP, Zhang Q. Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails.. Stem Cell Res Ther 2018 Mar 9;9(1):58.
- Seo MJ, Suh SY, Bae YC, Jung JS. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo.. Biochem Biophys Res Commun 2005 Mar 4;328(1):258-64.
- Saji Y, Tamura S, Yoshida Y, Kiso S, Iizuka AS, Matsumoto H, Kawasaki T, Kamada Y, Matsuzawa Y, Shinomura Y. Basic fibroblast growth factor promotes the trans-differentiation of mouse bone marrow cells into hepatic lineage cells via multiple liver-enriched transcription factors.. J Hepatol 2004 Oct;41(4):545-50.
- Talu00e9ns-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gu00f3mez-Lechu00f3n MJ. Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells.. World J Gastroenterol 2006 Sep 28;12(36):5834-45.
- Xu D, Nishimura T, Zheng M, Wu M, Su H, Sato N, Lee G, Michie S, Glenn J, Peltz G. Enabling autologous human liver regeneration with differentiated adipocyte stem cells.. Cell Transplant 2014;23(12):1573-84.
- Shao C, Yang X, Jing Y, Hou X, Huang Y, Zong C, Gao L, Liu W, Jiang J, Ye F, Shi J, Zhao Q, Li R, Zhang X, Wei L. The stemness of hepatocytes is maintained by high levels of lipopolysaccharide via YAP1 activation.. Stem Cell Res Ther 2021 Jun 10;12(1):342.
- Neubauer K, Wilfling T, Ritzel A, Ramadori G. Platelet-endothelial cell adhesion molecule-1 gene expression in liver sinusoidal endothelial cells during liver injury and repair.. J Hepatol 2000 Jun;32(6):921-32.
- Bird TG, Lorenzini S, Forbes SJ. Activation of stem cells in hepatic diseases.. Cell Tissue Res 2008 Jan;331(1):283-300.