Potential Use of Patient-Specific Induced Pluripotent Stem Cell for Liver Fibrosis Thalassemia Treatment Management

Susi Susanah; Wahyu Widowati; Nur Melani Sari; Revika Revika; Hanna Kusuma; Rizal Rizal; Ahmad Faried

doi:10.3889/oamjms.2022.8326

Authors

Susi Susanah Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Dr. Hasan Sadikin Hospital, Bandung, Indonesia
Wahyu Widowati Department of Pharmacology, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia
Nur Melani Sari Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Dr. Hasan Sadikin Hospital, Bandung, Indonesia; Oncology and Stem Cell Working Group, Universitas Padjadjaran, Dr. Hasan Sadikin Hospital, Bandung, Indonesia https://orcid.org/0000-0002-9062-9624
Revika Revika Department of Biotechnology, Faculty of Technobiology, Atma Jaya Catholic University of Indonesia, South Tangerang, Banten, Indonesia
Hanna Kusuma Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, Indonesia
Rizal Rizal Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, Indonesia; Department of Electrical Engineering, Biomedical Engineering, Faculty of Engineering, Universitas Indonesia, Depok, Indonesia
Ahmad Faried Oncology and Stem Cell Working Group, Universitas Padjadjaran, Dr. Hasan Sadikin Hospital, Bandung, Indonesia https://orcid.org/0000-0003-2967-8125

DOI:

https://doi.org/10.3889/oamjms.2022.8326

Keywords:

Thalassemia, Iron overload, Liver fibrosis, Induced pluripotent stem cells-hepatic stellate cells, Management

Abstract

Thalassemia is the most common inherited single gene blood disease worldwide and present a significant health problem in the world. Approximately, 1.5% of the global populations (An estimated 80–90 million people) are carriers of β-thalassemia. Around 5% of Indonesia population is thought to carry the thalassemia gene. The globin imbalance in β-thalassemia major causes hemolysis and ineffective erythropoiesis which results in anemia leading to increases of iron absorption. Furthermore, repeated blood transfusion and long-term increased iron absorption will lead to excessive accumulation of iron in vital organs, especially in the liver, causes liver fibrosis then leading to liver disease. Iron overload can be controlled by iron chelating drugs with the risk of side effects; therefore, a breakthrough is needed. Stem cell technology has a potential to provide novel insight in thalassemia major, through induced pluripotent stem cells (iPSCs) who has the ability to differentiate into hepatic stellate cells (HSCs)-like cells. iPSCs derived HSC-like cells (iPSC-HSCs) present the phenotypic and functional characteristics of HSCs. The utilization of iPSCs is a new option in personalized thalassemia management.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008;86(6):480-7. https://doi.org/10.2471/blt.06.036673 PMid:18568278

Wahidiyat, PA. Managing Thalassemia: Insight to Indonesian Practice. Bangkok, Thailand: Paper Presented at: The 30th Regional Congress of the ISBT; 2019. https://doi.org/10.1111/voxs.12544

Khandros E, Weiss MJ. Protein quality control during erythropoiesis and haemoglobin synthesis. Hematol Oncol Clin North Am. 2010;24(6):1071-88. https://doi.org/10.1016/j.hoc.2010.08.013 PMid:21075281

Cappellini MD, Farmakis D, Porter J, Taher A, editors. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 4th ed. Nicosia, Cyprus: Thalassaemia International Federation; 2021.

Anderson ER, Shah YM. Iron homeostasis in the liver. Compr Physiol. 2013;3(1):315-30. https://doi.org/10.1002/cphy.c120016 PMid:23720289

Chaston TB, Matak P, Pourvali K, Srai SK, McKie AT, Sharp PA. Hypoxia inhibits hepcidin expression in HuH7 hepatoma cells via decreased SMAD4 signaling. Cell Physiol. 2011;300(4):C888-95. https://doi.org/10.1152/ajpcell.00121.2010 PMid 21289291

Sikorska K, Bernat A, Wroblewska A. Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis. Hepatobiliary Pancreat Dis Int. 2016;15(5):461-79. https://doi.org/10.1016/s1499-3872(16)60135-2 PMid:27733315

Philippe MA, Ruddell RG, Ramm GA. Role of iron in hepatic fibrosis: One piece in the puzzle. World J Gastroenterol. 2007;13(35):4746-54. https://doi.org/10.3748/wjg.v13.i35.4746 PMid:17729396

Elalfy MS, Esmat G, Matter RM, Abdel Aziz HE, Massoud WA. Liver fibrosis in young Egyptian beta-thalassemia major patients: Relation to hepatitis C virus and compliance with chelation. Ann Hepatol. 2013;12(1):54-61. PMid:23293194

Mount NM, Ward SJ, Kefalas P, Hyllner J. Cell-based therapy technology classifications and translational challenges. Philos Trans R Soc Lond B Biol Sci. 2015;370(1680):20150017. https://doi.org/10.1098/rstb.2015.0017 PMid:26416686

Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: Past, present, and future. Stem Cell Res Ther. 2019;10(1):1-22. https://doi.org/10.1186/s13287-019-1165-5 PMid:30808416

Zomer HD, Vidane AS, Gonçalves NN, Ambrósio CE. Mesenchymal and induced pluripotent stem cells: General insights and clinical perspectives. Stem Cells Cloning. 2015;8:125-34. https://doi.org/10.2147/sccaa.S88036 PMid:26451119

Coll M, Perea L, Boon R, Leite SB, Vallverdú J, Mannaerts I, et al. Generation of hepatic stellate cells from human pluripotent stem cells enables in vitro modeling of liver fibrosis. Cell Stem Cell. 2018;23(1):101-13.e7. https://doi.org/10.1016/j.stem.2018.05.027 PMid:30049452

Yin C, Evason KJ, Asahina K, Stainier DY. Hepatic stellate cells in liver development, regeneration, and cancer. J Clin Invest. 2013;123(5):1902-10. https://doi.Org/10.1172/JCI66369 PMid:23635788

Aydinok Y. Thalassemia. Hematology. 2012;17(1):S28-31. https://doi.org/10.1179/102453312x13336169155295 PMid:22507773

Susanah S, Rakhmilla LE, Ghozali M, Trisaputra JO, Moestopo O, Sribudiani Y, et al. Iron status in newly diagnosed β-thalassemia major: High rate of iron status due to erythropoiesis drive. Biomed Res Int. 2021;26(1):221-4. https://doi.org/10.1155/2021/5560319 PMid:33954177

Motta I, Bou-Fakhredin R, Taher AT, Cappellini MD. Beta thalassemia: New therapeutic options beyond transfusion and iron chelation. Drugs. 2020;80(11):1053-63. https://doi.org/10.1007/s40265-020-01341-9 PMid:32557398

Lemischka I. Stem cell dogmas in the genomics era. Rev Clin Exp Hematol. 2001;5(1):15-25. https://doi.org/10.1046/j.1468-0734.2001.00030.x PMid:11486729

Jiang N, Chen M, Yang G, Xiang L, He L, Hei TK, et al. Hematopoietic stem cells in neural-crest derived bone marrow. Sci Rep. 2016;6(1):36411. https://doi.org/10.1038/srep36411 PMid:28000662

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76. https://doi.org/10.1016/j.cell.2006.07.024 PMid:16904174

Hu K. All roads lead to induced pluripotent stem cells: The technologies of iPSC generation. Stem Cells Dev. 2014;23(12):1285-300. https://doi.org/10.1089/scd.2013.0620 PMid:24524728

Hu S, Balakrishnan A, Bok RA, Anderton B, Larson PE, Nelson SJ, et al. 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. Cell Metab. 2011;14(1):131-42. https://doi.org/10.1016/j.cmet.2011.04.012 PMid:21723511

Chun YS, Byun K, Lee B. Induced pluripotent stem cells and personalized medicine: Current progress and future perspectives. Anat Cell Biol. 2011;44(4):245-55. https://doi.org/10.5115/acb.2011.44.4.245 PMid:22254153

Vallverdú J, de la Torre RA, Mannaerts I, Verhulst S, Smout A, Coll M, et al. Directed differentiation of human induced pluripotent stem cells to hepatic stellate cells. Nat Protoc. 2021;16(5):2542-63. https://doi.org/10.1038/s41596-021-00509-1 PMid:33864055

Cao Y, Ji C, Lu L. Mesenchymal stem cell therapy for liver fibrosis/cirrhosis. Ann Transl Med. 2020;8(8):562. https://doi.org/10.21037/atm.2020.02.119 PMid:32775363

Koui Y, Himeno M, Mori Y, Nakano Y, Saijou E, Tanimizu N, et al. Development of human iPSC-derived quiescent hepatic stellate cell-like cells for drug discovery and in vitro disease modeling. Stem Cell Rep. 2021;16(12):3050-63. https://doi.org/10.1016/j.stemcr.2021.11.002 PMid:34861166

Liu C, Oikonomopoulos A, Sayed N, Wu JC. Modeling human diseases with induced pluripotent stem cells: From 2D to 3D and beyond. Development. 2018;145(5):1-6. https://doi.org/10.1242/dev.156166 PMid:29519889

Zheng YL. Some ethical concerns about human induced pluripotent stem cells. Sci Eng Ethics. 2016;22(5):1277-84. https://doi.org/10.1007/s11948-015-9693-6 PMid:26276162

Ntai A, Baronchelli S, La Spada A, Moles A, Guffanti A, de Blasio P, et al. A review of research-grade human induced pluripotent stem cells qualification and biobanking processes. Biopreserv Biobank. 2017;15(4):384-92. https://doi.org/10.1089/bio.2016.0097 PMid:28388226

Luong MX, Smith KP, Crook JM, Stacey G. Biobanks for pluripotent stem cells. In: Jeanne L, Peterson SE, editors. Human Stem Cell Manual. California, US: Elsevier; 2012.

Lu X, Zhao T. Clinical therapy using iPSCs: Hopes and challenges. Genomics Proteomics Bioinformatics. 2013;11(5):294-98. https://doi.org/10.1016/j.gpb.2013.09.002 PMid:24060840