Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Availability, Functionality, and Safety as well as Quality Control of Hepatocytes as Seeding Cells in Liver Regenerative Medicine: State of the Art and Challenges

Author(s): Run-Tong Lian, An-Qi Zhuang, Jing Yue, Yan Chen, Kui-Fen Ma and Yi-Hang Wu*

Volume 18, Issue 8, 2023

Published on: 01 February, 2023

Page: [1090 - 1105] Pages: 16

DOI: 10.2174/1574888X18666230125113254

Price: $65

Abstract

Hepatic disease is one of the most common causes of death worldwide and has become a global health problem. Liver transplantation is the only effective treatment strategy for patients with hepatic function failure, but the insufficient number of donated healthy livers is the main obstacle limiting this process. To alleviate the demand for donor's livers, alternative approaches are being actively explored using liver tissue engineering principles. Liver tissue engineering consists of three elements, including seeding cells, extracellular matrix, and bioreactors. Among them, seeding cell is the most key factor. In this regard, hepatocyte-based tissue engineering can overcome the above shortages for tissue repair and regeneration in hepatic disorders. Primary human hepatocytes in liver regenerative medicine are the most preferred seeding cells, although limited access to a sufficient number of functional hepatocytes are a major issue due to the difficulties in long-term function maintenance of hepatocyte as well as the lack of availability of healthy donors. Hepatocyte-like cells (HLCs), derived from various stem cells, including non-liver-derived stem cells and liver-derived stem cells, as well as trans-differentiation of other cell types, may provide adequate cell sources and could replace primary human hepatocytes as seeding cells. However, it is still a great difficulty that HLCs generated by stem cell differentiation meet the quality required for clinical therapy. Furthermore, none of the standardized protocols to generate high-quality HLCs is available. Whether primary hepatocytes or HLCs are from various sources, preventing the functional deterioration of hepatocytes or generating fully functional hepatocytes is also a big challenge, respectively. In addition, the adoptions of three-dimensional co-culture systems and some small-molecule compounds contribute to maintaining the hepatic functionality of primary hepatocytes and enhancing the liver-specific functions of HLCs. In short, hepatocyte-based liver regenerative medicine is an attractive alternative strategy for liver diseases, notwithstanding some challenges still exist from bench to bedside. This review summarizes the current status, issues, and challenges in availability, functionality, and safety, as well as quality control of seeding hepatocytes with regard to liver tissue engineering in regenerative medicine for the treatment of liver disorders.

« Previous Next »
Graphical Abstract

[1]
Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol 2017; 27(21): R1147-51.
[http://dx.doi.org/10.1016/j.cub.2017.09.019] [PMID: 29112863]
[2]
Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol 2019; 70(1): 151-71.
[http://dx.doi.org/10.1016/j.jhep.2018.09.014] [PMID: 30266282]
[3]
Song ATW, Avelino-Silva VI, Pecora RA, Pugliese V, D’Albuquerque LA, Abdala E. Liver transplantation: Fifty years of experience. World J Gastroenterol 2014; 20(18): 5363-74.
[http://dx.doi.org/10.3748/wjg.v20.i18.5363] [PMID: 24833866]
[4]
Soltys KA, Setoyama K, Tafaleng EN, et al. Host conditioning and rejection monitoring in hepatocyte transplantation in humans. J Hepatol 2017; 66(5): 987-1000.
[http://dx.doi.org/10.1016/j.jhep.2016.12.017] [PMID: 28027971]
[5]
Ananthanarayanan A, Narmada BC, Mo X, McMillian M, Yu H. Purpose-driven biomaterials research in liver-tissue engineering. Trends Biotechnol 2011; 29(3): 110-8.
[http://dx.doi.org/10.1016/j.tibtech.2010.10.006] [PMID: 21129798]
[6]
Toh YC, Zhang C, Zhang J, et al. A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip 2007; 7(3): 302-9.
[http://dx.doi.org/10.1039/b614872g] [PMID: 17330160]
[7]
Muraca M, Gerunda G, Neri D, et al. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet 2002; 359(9303): 317-8.
[http://dx.doi.org/10.1016/S0140-6736(02)07529-3] [PMID: 11830200]
[8]
Rifai K, Ernst T, Kretschmer U, et al. Prometheus® - a new extracorporeal system for the treatment of liver failure. J Hepatol 2003; 39(6): 984-90.
[http://dx.doi.org/10.1016/S0168-8278(03)00468-9] [PMID: 14642616]
[9]
Morsiani E, Brogli M, Galavotti D, Pazzi P, Puviani AC, Azzena GF. Biologic liver support: Optimal cell source and mass. Int J Artif Organs 2002; 25(10): 985-93.
[http://dx.doi.org/10.1177/039139880202501013] [PMID: 12456040]
[10]
Chan C, Berthiaume F, Nath BD, Tilles AW, Toner M, Yarmush ML. Hepatic tissue engineering for adjunct and temporary liver support: Critical technologies. Liver Transpl 2004; 10(11): 1331-42.
[http://dx.doi.org/10.1002/lt.20229] [PMID: 15497161]
[11]
Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: From liver transplantation to cell factory. J Hepatol 2015; 62(S1): S157-69.
[http://dx.doi.org/10.1016/j.jhep.2015.02.040] [PMID: 25920085]
[12]
Miki T. Clinical hepatocyte transplantation. Gastroenterol Hepatol 2019; 42(3): 202-8.
[http://dx.doi.org/10.1016/j.gastrohep.2018.10.007] [PMID: 30470565]
[13]
Mei J, Sgroi A, Mai G, et al. Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice. Cell Transplant 2009; 18(1): 101-10.
[http://dx.doi.org/10.3727/096368909788237168] [PMID: 19476213]
[14]
Mai G, Huy NT, Morel P, et al. Treatment of fulminant liver failure by transplantation of microencapsulated primary or immortalized xenogeneic hepatocytes. Transplant Proc 2005; 37(1): 527-9.
[http://dx.doi.org/10.1016/j.transproceed.2005.01.017] [PMID: 15808699]
[15]
Link TW, Arifin DR, Long CM, et al. Use of magnetocapsules for in vivo visualization and enhanced survival of xenogeneic HepG2 cell transplants. Cell Med 2012; 4(2): 77-84.
[http://dx.doi.org/10.3727/215517912X653337] [PMID: 23293747]
[16]
Ribes-Koninckx C, Ibars EP, Agrasot MÁC, et al. Clinical outcome of hepatocyte transplantation in four pediatric patients with inherited metabolic diseases. Cell Transplant 2012; 21(10): 2267-82.
[http://dx.doi.org/10.3727/096368912X637505] [PMID: 23231960]
[17]
McKiernan P. Liver transplantation and cell therapies for inborn errors of metabolism. J Inherit Metab Dis 2013; 36(4): 675-80.
[http://dx.doi.org/10.1007/s10545-012-9581-z] [PMID: 23296369]
[18]
Knobeloch D, Ehnert S, Schyschka L, et al. Human hepatocytes: Isolation, culture, and quality procedures. Methods Mol Biol 2012; 806: 99-120.
[http://dx.doi.org/10.1007/978-1-61779-367-7_8] [PMID: 22057448]
[19]
Fox I, Roy-Chowdhury J. Hepatocyte transplantation. J Hepatol 2004; 40(6): 878-86.
[http://dx.doi.org/10.1016/j.jhep.2004.04.009] [PMID: 15158325]
[20]
Mazariegos G, Shneider B, Burton B, et al. Liver transplantation for pediatric metabolic disease. Mol Genet Metab 2014; 111(4): 418-27.
[http://dx.doi.org/10.1016/j.ymgme.2014.01.006] [PMID: 24495602]
[21]
Gramignoli R, Tahan V, Dorko K, et al. New potential cell source for hepatocyte transplantation: Discarded livers from metabolic disease liver transplants. Stem Cell Res 2013; 11(1): 563-73.
[http://dx.doi.org/10.1016/j.scr.2013.03.002] [PMID: 23644508]
[22]
Hewitt NJ. Optimisation of the cryopreservation of primary hepatocytes. Methods Mol Biol 2010; 640: 83-105.
[http://dx.doi.org/10.1007/978-1-60761-688-7_4] [PMID: 20645047]
[23]
Gómez-Lechón M, Donato M, Castell J, Jover R. Human hepatocytes as a tool for studying toxicity and drug metabolism. Curr Drug Metab 2003; 4(4): 292-312.
[http://dx.doi.org/10.2174/1389200033489424] [PMID: 12871046]
[24]
Griffith LG, Naughton G. Tissue engineering-current challenges and expanding opportunities. Science 2002; 295(5557): 1009-14.
[http://dx.doi.org/10.1126/science.1069210] [PMID: 11834815]
[25]
MacPherson D, Bram Y, Park J, Schwartz RE. Peptide-based scaffolds for the culture and maintenance of primary human hepatocytes. Sci Rep 2021; 11(1): 6772.
[http://dx.doi.org/10.1038/s41598-021-86016-5] [PMID: 33762604]
[26]
Wege H, Le HT, Chui MS, et al. Telomerase reconstitution immortalizes human fetal hepatocytes without disrupting their differentiation potential. Gastroenterology 2003; 124(2): 432-44.
[http://dx.doi.org/10.1053/gast.2003.50064] [PMID: 12557149]
[27]
Poyck PPC, van Wijk ACWA, van der Hoeven TV, et al. Evaluation of a new immortalized human fetal liver cell line (cBAL111) for application in bioartificial liver. J Hepatol 2008; 48(2): 266-75.
[http://dx.doi.org/10.1016/j.jhep.2007.09.018] [PMID: 18093687]
[28]
Poyck PPC, Hoekstra R, van Wijk ACWA, et al. Functional and morphological comparison of three primary liver cell types cultured in the AMC bioartificial liver. Liver Transpl 2007; 13(4): 589-98.
[http://dx.doi.org/10.1002/lt.21090] [PMID: 17394165]
[29]
Deurholt T, van Til NP, Chhatta AA, et al. Novel immortalized human fetal liver cell line, cBAL111, has the potential to differentiate into functional hepatocytes. BMC Biotechnol 2009; 9(1): 89.
[http://dx.doi.org/10.1186/1472-6750-9-89] [PMID: 19845959]
[30]
Chen Y, Li J, Liu X, Zhao W, Wang Y, Wang X. Transplantation of immortalized human fetal hepatocytes prevents acute liver failure in 90% hepatectomized mice. Transplant Proc 2010; 42(5): 1907-14.
[http://dx.doi.org/10.1016/j.transproceed.2010.01.061] [PMID: 20620547]
[31]
Khan AA, Habeeb A, Parveen N, et al. Peritoneal transplantation of human fetal hepatocytes for the treatment of acute fatty liver of pregnancy: A case report. Trop Gastroenterol 2004; 25(3): 141-3.
[PMID: 15682663]
[32]
Chinnici CM, Timoneri F, Amico G, et al. Characterization of liver-specific functions of human fetal hepatocytes in culture. Cell Transplant 2015; 24(6): 1139-53.
[http://dx.doi.org/10.3727/096368914X680082] [PMID: 24667036]
[33]
Ramboer E, Vanhaecke T, Rogiers V, Vinken M. Immortalized human hepatic cell lines for in vitro testing and research purposes. Methods Mol Biol 2015; 1250: 53-76.
[http://dx.doi.org/10.1007/978-1-4939-2074-7_4] [PMID: 26272134]
[34]
Li J, Li LJ, Cao HC, et al. Establishment of highly differentiated immortalized human hepatocyte line with simian virus 40 large tumor antigen for liver based cell therapy. ASAIO J 2005; 51(3): 262-8.
[http://dx.doi.org/10.1097/01.MAT.0000161045.16805.8B] [PMID: 15968957]
[35]
Reid Y, Gaddipati JP, Yadav D, Kantor J. Establishment of a human neonatal hepatocyte cell line. In Vitro Cell Dev Biol Anim 2009; 45(9): 535-42.
[http://dx.doi.org/10.1007/s11626-009-9219-0] [PMID: 19565302]
[36]
Tsuruga Y, Kiyono T, Matsushita M, Takahashi T, Kasai H, Todo S. Establishment of immortalized human hepatocytes by introduction of HPV16 E6/E7 and hTERT as cell sources for liver cell-based therapy. Cell Transplant 2008; 17(9): 1083-94.
[http://dx.doi.org/10.3727/096368908786991542]
[37]
Kobayashi N, Okitsu T, Tanaka N. Cell choice for bioartificial livers. Keio J Med 2003; 52(3): 151-7.
[http://dx.doi.org/10.2302/kjm.52.151] [PMID: 14529147]
[38]
Noguchi H, Kobayashi N, Westerman KA, et al. Controlled expansion of human endothelial cell populations by Cre-loxP-based reversible immortalization. Hum Gene Ther 2002; 13(2): 321-34.
[http://dx.doi.org/10.1089/10430340252769833] [PMID: 11812287]
[39]
Watanabe T, Shibata N, Westerman KA, et al. Establishment of immortalized human hepatic stellate scavenger cells to develop bioartificial livers1. Transplantation 2003; 75(11): 1873-80.
[http://dx.doi.org/10.1097/01.TP.0000064621.50907.A6] [PMID: 12811248]
[40]
Oldhafer F, Bock M, Falk CS, Vondran FWR. Immunological aspects of liver cell transplantation. World J Transplant 2016; 6(1): 42-53.
[http://dx.doi.org/10.5500/wjt.v6.i1.42] [PMID: 27011904]
[41]
Zakikhan K, Pournasr B, Vosough M, Nassiri-Asl M. In vitro generated hepatocyte-like cells: A novel tool in regenerative medicine and drug discovery. Cell J 2017; 19(2): 204-17.
[PMID: 28670513]
[42]
Saito Y, Ikemoto T, Morine Y, Shimada M. Current status of hepatocyte-like cell therapy from stem cells. Surg Today 2021; 51(3): 340-9.
[http://dx.doi.org/10.1007/s00595-020-02092-6] [PMID: 32754843]
[43]
Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. Embryonic stem cell lines from human blastocysts: Somatic differentiation in vitro. Nat Biotechnol 2000; 18(4): 399-404.
[http://dx.doi.org/10.1038/74447] [PMID: 10748519]
[44]
Behbahan IS, Duan Y, Lam A, et al. New approaches in the differentiation of human embryonic stem cells and induced pluripotent stem cells toward hepatocytes. Stem Cell Rev 2011; 7(3): 748-59.
[http://dx.doi.org/10.1007/s12015-010-9216-4] [PMID: 21336836]
[45]
Oh SKW, Chen AK, Mok Y, et al. Long-term microcarrier suspension cultures of human embryonic stem cells. Stem Cell Res 2009; 2(3): 219-30.
[http://dx.doi.org/10.1016/j.scr.2009.02.005] [PMID: 19393590]
[46]
Hay DC, Fletcher J, Payne C, et al. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci 2008; 105(34): 12301-6.
[http://dx.doi.org/10.1073/pnas.0806522105] [PMID: 18719101]
[47]
Touboul T, Hannan NRF, Corbineau S, et al. Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 2010; 51(5): 1754-65.
[http://dx.doi.org/10.1002/hep.23506] [PMID: 20301097]
[48]
Li Z, Wu J, Wang L, et al. Generation of qualified clinical-grade functional hepatocytes from human embryonic stem cells in chemically defined conditions. Cell Death Dis 2019; 10(10): 763.
[http://dx.doi.org/10.1038/s41419-019-1967-5] [PMID: 31601782]
[49]
Zhou Q, Xie X, Zhong Z, Sun P, Zhou X. An efficient method for directed hepatocyte-like cell induction from human embryonic stem cells. J Vis Exp 2021; 171: 62654.
[http://dx.doi.org/10.3791/62654] [PMID: 34028444]
[50]
Zhou W, Hannoun Z, Jaffray E, et al. SUMOylation of HNF4α regulates protein stability and hepatocyte function. J Cell Sci 2012; 125(15): 3630-5.
[http://dx.doi.org/10.1242/jcs.102889] [PMID: 22505616]
[51]
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.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[52]
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5): 861-72.
[http://dx.doi.org/10.1016/j.cell.2007.11.019] [PMID: 18035408]
[53]
Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008; 26(1): 101-6.
[http://dx.doi.org/10.1038/nbt1374] [PMID: 18059259]
[54]
Asgari S, Moslem M, Bagheri-Lankarani K, Pournasr B, Miryounesi M, Baharvand H. Differentiation and transplantation of human induced pluripotent stem cell-derived hepatocyte-like cells. Stem Cell Rev 2013; 9(4): 493-504.
[http://dx.doi.org/10.1007/s12015-011-9330-y] [PMID: 22076752]
[55]
Baxter M, Withey S, Harrison S, et al. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes. J Hepatol 2015; 62(3): 581-9.
[http://dx.doi.org/10.1016/j.jhep.2014.10.016] [PMID: 25457200]
[56]
Sullivan GJ, Hay DC, Park IH, et al. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 2010; 51(1): 329-35.
[http://dx.doi.org/10.1002/hep.23335] [PMID: 19877180]
[57]
Messina A, Luce E, Benzoubir N, et al. Evidence of adult features and functions of hepatocytes differentiated from human induced pluripotent stem cells and self-organized as organoids. Cells 2022; 11(3): 537.
[http://dx.doi.org/10.3390/cells11030537] [PMID: 35159346]
[58]
Deguchi S, Takayama K, Mizuguchi H. Generation of human induced pluripotent stem cell-derived hepatocyte-like cells for cellular medicine. Biol Pharm Bull 2020; 43(4): 608-15.
[http://dx.doi.org/10.1248/bpb.b19-00740] [PMID: 32238703]
[59]
Sipp D, Robey PG, Turner L. Clear up this stem-cell mess. Nature 2018; 561(7724): 455-7.
[http://dx.doi.org/10.1038/d41586-018-06756-9] [PMID: 30258150]
[60]
Caulfield T, Sipp D, Murry CE, Daley GQ, Kimmelman J. Confronting stem cell hype. Science 2016; 352(6287): 776-7.
[http://dx.doi.org/10.1126/science.aaf4620] [PMID: 27174977]
[61]
Hu C, Zhao L, Li L. Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases. Stem Cell Res Ther 2019; 10(1): 199.
[http://dx.doi.org/10.1186/s13287-019-1310-1] [PMID: 31287024]
[62]
Shi D, Zhang J, Zhou Q, et al. Quantitative evaluation of human bone mesenchymal stem cells rescuing fulminant hepatic failure in pigs. Gut 2017; 66(5): 955-64.
[http://dx.doi.org/10.1136/gutjnl-2015-311146] [PMID: 26884426]
[63]
Chen L, Qu J, Cheng T, Chen X, Xiang C. Menstrual blood-derived stem cells: toward therapeutic mechanisms, novel strategies, and future perspectives in the treatment of diseases. Stem Cell Res Ther 2019; 10(1): 406.
[http://dx.doi.org/10.1186/s13287-019-1503-7] [PMID: 31864423]
[64]
Volarevic V, Markovic BS, Gazdic M, et al. Ethical and safety issues of stem cell-based therapy. Int J Med Sci 2018; 15(1): 36-45.
[http://dx.doi.org/10.7150/ijms.21666] [PMID: 29333086]
[65]
Barkholt L, Flory E, Jekerle V, et al. Risk of tumorigenicity in mesenchymal stromal cell-based therapies—Bridging scientific observations and regulatory viewpoints. Cytotherapy 2013; 15(7): 753-9.
[http://dx.doi.org/10.1016/j.jcyt.2013.03.005] [PMID: 23602595]
[66]
Jiang W, Xu J. Immune modulation by mesenchymal stem cells. Cell Prolif 2020; 53(1): e12712.
[http://dx.doi.org/10.1111/cpr.12712] [PMID: 31730279]
[67]
L PK, Kandoi S, Misra R, S V, K R, Verma RS.. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev 2019; 46: 1-9.
[http://dx.doi.org/10.1016/j.cytogfr.2019.04.002] [PMID: 30954374]
[68]
Hu C, Zhao L, Zhang L, Bao Q, Li L. Mesenchymal stem cell-based cell-free strategies: Safe and effective treatments for liver injury. Stem Cell Res Ther 2020; 11(1): 377.
[http://dx.doi.org/10.1186/s13287-020-01895-1] [PMID: 32883343]
[69]
Beer L, Mildner M, Ankersmit HJ. Cell secretome based drug substances in regenerative medicine: When regulatory affairs meet basic science. Ann Transl Med 2017; 5(7): 170.
[http://dx.doi.org/10.21037/atm.2017.03.50] [PMID: 28480206]
[70]
Piryaei A, Valojerdi MR, Shahsavani M, Baharvand H. Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells on nanofibers and their transplantation into a carbon tetrachloride-induced liver fibrosis model. Stem Cell Rev 2011; 7(1): 103-18.
[http://dx.doi.org/10.1007/s12015-010-9126-5] [PMID: 20182823]
[71]
di Bonzo LV, Ferrero I, Cravanzola C, et al. Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: Engraftment and hepatocyte differentiation versus profibrogenic potential. Gut 2008; 57(2): 223-31.
[http://dx.doi.org/10.1136/gut.2006.111617] [PMID: 17639088]
[72]
Piscaglia AC, Di Campli C, Zocco MA, et al. Human cordonal stem cell intraperitoneal injection can represent a rescue therapy after an acute hepatic damage in immunocompetent rats. Transplant Proc 2005; 37(6): 2711-4.
[http://dx.doi.org/10.1016/j.transproceed.2005.06.076] [PMID: 16182791]
[73]
Chien CC, Yen BL, Lee FK, et al. In vitro differentiation of human placenta-derived multipotent cells into hepatocyte-like cells. Stem Cells 2006; 24(7): 1759-68.
[http://dx.doi.org/10.1634/stemcells.2005-0521] [PMID: 16822884]
[74]
Alatyyat SM, Alasmari HM, Aleid OA, Abdel-maksoud MS, Elsherbiny N. Umbilical cord stem cells: Background, processing and applications. Tissue Cell 2020; 65: 101351.
[http://dx.doi.org/10.1016/j.tice.2020.101351] [PMID: 32746993]
[75]
Ishkitiev N, Yaegaki K, Imai T, et al. High-purity hepatic lineage differentiated from dental pulp stem cells in serum-free medium. J Endod 2012; 38(4): 475-80.
[http://dx.doi.org/10.1016/j.joen.2011.12.011] [PMID: 22414832]
[76]
Gan L, Liu Y, Cui D, Pan Y, Zheng L, Wan M. Dental tissue-derived human mesenchymal stem cells and their potential in therapeutic application. Stem Cells Int 2020; 2020: 8864572.
[http://dx.doi.org/10.1155/2020/8864572] [PMID: 32952572]
[77]
Gil-Recio C, Montori S, Al Demour S, et al. Chemically defined conditions mediate an efficient induction of dental pulp pluripotent-like stem cells into hepatocyte-like cells. Stem Cells Int 2021; 2021: 5212852.
[http://dx.doi.org/10.1155/2021/5212852] [PMID: 34795766]
[78]
Probert PME, Chung GW, Cockell SJ, et al. Utility of B-13 progenitor-derived hepatocytes in hepatotoxicity and genotoxicity studies. Toxicol Sci 2014; 137(2): 350-70.
[http://dx.doi.org/10.1093/toxsci/kft258] [PMID: 24235770]
[79]
Wang RYL, Shen CN, Lin MH, Tosh D, Shih C. Hepatocyte-like cells transdifferentiated from a pancreatic origin can support replication of hepatitis B virus. J Virol 2005; 79(20): 13116-28.
[http://dx.doi.org/10.1128/JVI.79.20.13116-13128.2005] [PMID: 16189013]
[80]
Wallace K, Fairhall EA, Charlton KA, Wright MC. AR42J-B-13 cell: An expandable progenitor to generate an unlimited supply of functional hepatocytes. Toxicology 2010; 278(3): 277-87.
[http://dx.doi.org/10.1016/j.tox.2010.05.008] [PMID: 20685382]
[81]
Bozdağ SC, Yüksel MK, Demirer T. Adult stem cells and medicine. Adv Exp Med Biol 2018; 1079: 17-36.
[http://dx.doi.org/10.1007/5584_2018_184] [PMID: 29556955]
[82]
Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000; 6(11): 1229-34.
[http://dx.doi.org/10.1038/81326] [PMID: 11062533]
[83]
Yannaki E, Athanasiou E, Xagorari A, et al. G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs. Exp Hematol 2005; 33(1): 108-19.
[http://dx.doi.org/10.1016/j.exphem.2004.09.005] [PMID: 15661404]
[84]
Newsome PN, Johannessen I, Boyle S, et al. Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion. Gastroenterology 2003; 124(7): 1891-900.
[http://dx.doi.org/10.1016/S0016-5085(03)00401-3] [PMID: 12806622]
[85]
Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003; 422(6934): 901-4.
[http://dx.doi.org/10.1038/nature01539] [PMID: 12665833]
[86]
Irudayaswamy A, Muthiah M, Zhou L, et al. Long-term fate of human fetal liver progenitor cells transplanted in injured mouse livers. Stem Cells 2018; 36(1): 103-13.
[http://dx.doi.org/10.1002/stem.2710] [PMID: 28960647]
[87]
Takase HM, Itoh T, Ino S, et al. FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration. Genes Dev 2013; 27(2): 169-81.
[http://dx.doi.org/10.1101/gad.204776.112] [PMID: 23322300]
[88]
Lu WY, Bird TG, Boulter L, et al. Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nat Cell Biol 2015; 17(8): 971-83.
[http://dx.doi.org/10.1038/ncb3203] [PMID: 26192438]
[89]
Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 2013; 494(7436): 247-50.
[http://dx.doi.org/10.1038/nature11826] [PMID: 23354049]
[90]
Huch M, Gehart H, van Boxtel R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 2015; 160(1-2): 299-312.
[http://dx.doi.org/10.1016/j.cell.2014.11.050] [PMID: 25533785]
[91]
Fausto N. Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells. Hepatology 2004; 39(6): 1477-87.
[http://dx.doi.org/10.1002/hep.20214] [PMID: 15185286]
[92]
Shi J, Han G, Wang J, et al. Matrine promotes hepatic oval cells differentiation into hepatocytes and alleviates liver injury by suppression of Notch signalling pathway. Life Sci 2020; 261: 118354.
[http://dx.doi.org/10.1016/j.lfs.2020.118354] [PMID: 32866517]
[93]
Wang P, Cong M, Liu TH, et al. Primary isolated hepatic oval cells maintain progenitor cell phenotypes after two-year prolonged cultivation. J Hepatol 2010; 53(5): 863-71.
[http://dx.doi.org/10.1016/j.jhep.2010.05.014] [PMID: 20739084]
[94]
Dumble ML, Croager EJ, Yeoh GCT, Quail EA. Generation and characterization of p53 null transformed hepatic progenitor cells: Oval cells give rise to hepatocellular carcinoma. Carcinogenesis 2002; 23(3): 435-45.
[http://dx.doi.org/10.1093/carcin/23.3.435] [PMID: 11895858]
[95]
Mahieu-Caputo D, Allain JE, Branger J, et al. Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts. Hum Gene Ther 2004; 15(12): 1219-28.
[http://dx.doi.org/10.1089/hum.2004.15.1219] [PMID: 15684698]
[96]
Malhi H, Irani AN, Gagandeep S, Gupta S. Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes. J Cell Sci 2002; 115(13): 2679-88.
[http://dx.doi.org/10.1242/jcs.115.13.2679] [PMID: 12077359]
[97]
Suzuki A, Zheng YW, Kondo R, et al. Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology 2000; 32(6): 1230-9.
[http://dx.doi.org/10.1053/jhep.2000.20349] [PMID: 11093729]
[98]
Anzai K, Tsuruya K, Ida K, Kagawa T, Inagaki Y, Kamiya A. Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts. Sci Rep 2021; 11(1): 18551.
[http://dx.doi.org/10.1038/s41598-021-97937-6] [PMID: 34535735]
[99]
Gordon GJ, Coleman WB, Hixson DC, Grisham JW. Liver regeneration in rats with retrorsine-induced hepatocellular injury proceeds through a novel cellular response. Am J Pathol 2000; 156(2): 607-19.
[http://dx.doi.org/10.1016/S0002-9440(10)64765-7] [PMID: 10666390]
[100]
Gordon GJ, Coleman WB, Grisham JW. Temporal analysis of hepatocyte differentiation by small hepatocyte-like progenitor cells during liver regeneration in retrorsine-exposed rats. Am J Pathol 2000; 157(3): 771-86.
[http://dx.doi.org/10.1016/S0002-9440(10)64591-9] [PMID: 10980117]
[101]
Hunter Best D, Coleman WB. Cells of origin of small hepatocyte-like progenitor cells in the retrorsine model of rat liver injury and regeneration. J Hepatol 2008; 48(2): 369-71.
[http://dx.doi.org/10.1016/j.jhep.2007.11.002] [PMID: 18086505]
[102]
Mitaka T, Ichinohe N, Kon J, et al. Thy1‐positive cell transplantation activates the growth of small hepatocyte‐like progenitor cells in rat livers treated with retrorsine and PH. FASEB J 2013; 27(S1): 257.
[http://dx.doi.org/10.1096/fasebj.27.1_supplement.257.7]
[103]
Best DH, Coleman WB. Bile duct destruction by 4,4′-diaminodiphenylmethane does not block the small hepatocyte-like progenitor cell response in retrorsine-exposed rats. Hepatology 2007; 46(5): 1611-9.
[http://dx.doi.org/10.1002/hep.21876] [PMID: 17705295]
[104]
Best DH, Coleman WB. Treatment with 2-AAF blocks the small hepatocyte-like progenitor cell response in retrorsine-exposed rats. J Hepatol 2007; 46(6): 1055-63.
[http://dx.doi.org/10.1016/j.jhep.2007.01.040] [PMID: 17434228]
[105]
Wang Z, Li W, Li C, et al. Small hepatocyte-like progenitor cells may be a Hedgehog signaling pathway-controlled subgroup of liver stem cells. Exp Ther Med 2016; 12(4): 2423-30.
[http://dx.doi.org/10.3892/etm.2016.3675] [PMID: 27703504]
[106]
Gordon GJ, Butz GM, Grisham JW, Coleman WB. Isolation, short-term culture, and transplantation of small hepatocyte-like progenitor cells from retrorsine-exposed rats1. Transplantation 2002; 73(8): 1236-43.
[http://dx.doi.org/10.1097/00007890-200204270-00008] [PMID: 11981414]
[107]
Sekiya S, Suzuki A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 2011; 475(7356): 390-3.
[http://dx.doi.org/10.1038/nature10263] [PMID: 21716291]
[108]
Huang P, He Z, Ji S, et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 2011; 475(7356): 386-9.
[http://dx.doi.org/10.1038/nature10116] [PMID: 21562492]
[109]
Sancho-Martinez I, Baek SH, Izpisua BJC. Lineage conversion methodologies meet the reprogramming toolbox. Nat Cell Biol 2012; 14(9): 892-9.
[http://dx.doi.org/10.1038/ncb2567] [PMID: 22945254]
[110]
Pournasr B, Asghari-Vostikolaee MH, Baharvand H. Transcription factor-mediated reprograming of fibroblasts to hepatocyte-like cells. Eur J Cell Biol 2015; 94(12): 603-10.
[http://dx.doi.org/10.1016/j.ejcb.2015.10.003] [PMID: 26561000]
[111]
Huang P, Zhang L, Gao Y, et al. Direct reprogramming of human fibroblasts to functional and expandable hepatocytes. Cell Stem Cell 2014; 14(3): 370-84.
[http://dx.doi.org/10.1016/j.stem.2014.01.003] [PMID: 24582927]
[112]
Park S, In Hwang S, Kim J, et al. The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis. Stem Cell Res Ther 2019; 10(1): 21.
[http://dx.doi.org/10.1186/s13287-018-1127-3] [PMID: 30635054]
[113]
Bai Y, Yang Z, Xu X, et al. Direct chemical induction of hepatocyte‐like cells with capacity for liver repopulation. Hepatology 2022; hep.32686.
[http://dx.doi.org/10.1002/hep.32686] [PMID: 35881538]
[114]
Orge ID, Gadd VL, Barouh JL, et al. Phenotype instability of hepatocyte-like cells produced by direct reprogramming of mesenchymal stromal cells. Stem Cell Res Ther 2020; 11(1): 154.
[http://dx.doi.org/10.1186/s13287-020-01665-z] [PMID: 32276654]
[115]
Guo R, Tang W, Yuan Q, Hui L, Wang X, Xie X. Chemical cocktails enable hepatic reprogramming of mouse fibroblasts with a single transcription factor. Stem Cell Reports 2017; 9(2): 499-512.
[http://dx.doi.org/10.1016/j.stemcr.2017.06.013] [PMID: 28757167]
[116]
Katsuda T, Kawamata M, Inoue A, Yamaguchi T, Abe M, Ochiya T. Long‐term maintenance of functional primary human hepatocytes using small molecules. FEBS Lett 2020; 594(1): 114-25.
[http://dx.doi.org/10.1002/1873-3468.13582] [PMID: 31432507]
[117]
Kim Y, Jeong J, Choi D. Small-molecule-mediated reprogramming: A silver lining for regenerative medicine. Exp Mol Med 2020; 52(2): 213-26.
[http://dx.doi.org/10.1038/s12276-020-0383-3] [PMID: 32080339]
[118]
Olinga P, Meijer DKF, Slooff MJH, Groothuis GMM. Liver slices in in vitro pharmacotoxicology with special reference to the use of human liver tissue. Toxicol In Vitro 1997; 12(1): 77-100.
[http://dx.doi.org/10.1016/S0887-2333(97)00097-0] [PMID: 20654390]
[119]
Kammerer S, Küpper JH. Human hepatocyte systems for in vitro toxicology analysis. J Cell Biotechnol 2018; 3(2): 85-93.
[http://dx.doi.org/10.3233/JCB-179012]
[120]
Godoy P, Hewitt NJ, Albrecht U, et al. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 2013; 87(8): 1315-530.
[http://dx.doi.org/10.1007/s00204-013-1078-5] [PMID: 23974980]
[121]
Tateno C, Yoshizane Y, Saito N, et al. Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am J Pathol 2004; 165(3): 901-12.
[http://dx.doi.org/10.1016/S0002-9440(10)63352-4] [PMID: 15331414]
[122]
Sato Y, Yamada H, Iwasaki K, et al. Human hepatocytes can repopulate mouse liver: Histopathology of the liver in human hepatocyte-transplanted chimeric mice and toxicologic responses to acetaminophen. Toxicol Pathol 2008; 36(4): 581-91.
[http://dx.doi.org/10.1177/0192623308318212] [PMID: 18467679]
[123]
Hickey RD, Mao SA, Glorioso J, et al. Curative ex vivo liver-directed gene therapy in a pig model of hereditary tyrosinemia type 1. Sci Transl Med 2016; 8(349): 349ra99.
[http://dx.doi.org/10.1126/scitranslmed.aaf3838] [PMID: 27464750]
[124]
Khan Z, Strom SC. Hepatocyte transplantation in special populations: Clinical use in children. Methods Mol Biol 2017; 1506: 3-16.
[http://dx.doi.org/10.1007/978-1-4939-6506-9_1] [PMID: 27830542]
[125]
Dhawan A, Chaijitraruch N, Fitzpatrick E, et al. Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children. J Hepatol 2020; 72(5): 877-84.
[http://dx.doi.org/10.1016/j.jhep.2019.12.002] [PMID: 31843649]
[126]
Dhawan A. Clinical human hepatocyte transplantation: Current status and challenges. Liver Transpl 2015; 21(S1): S39-44.
[http://dx.doi.org/10.1002/lt.24226] [PMID: 26249755]
[127]
Puppi J, Strom SC, Hughes RD, et al. Improving the techniques for human hepatocyte transplantation: Report from a consensus meeting in London. Cell Transplant 2012; 21(1): 1-10.
[http://dx.doi.org/10.3727/096368911X566208] [PMID: 21457616]
[128]
Ballet F, Bouma ME, Wang SR, Amit N, Marais J, Infante R. Isolation, culture and characterization of adult human hepatocytes from surgical liver biopsies. Hepatology 1984; 4(5): 849-54.
[http://dx.doi.org/10.1002/hep.1840040509] [PMID: 6090291]
[129]
Alexandrova K, Griesel C, Barthold M, et al. Large-scale isolation of human hepatocytes for therapeutic application. Cell Transplant 2005; 14(10): 845-53.
[http://dx.doi.org/10.3727/000000005783982530] [PMID: 16454359]
[130]
Pfeiffer E, Kegel V, Zeilinger K, et al. Featured Article: Isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells. Exp Biol Med 2015; 240(5): 645-56.
[http://dx.doi.org/10.1177/1535370214558025] [PMID: 25394621]
[131]
Klaas M, Möll K, Mäemets-Allas K, Loog M, Järvekülg M, Jaks V. Long-term maintenance of functional primary human hepatocytes in 3D gelatin matrices produced by solution blow spinning. Sci Rep 2021; 11(1): 20165.
[http://dx.doi.org/10.1038/s41598-021-99659-1] [PMID: 34635750]
[132]
Kegel V, Deharde D, Pfeiffer E, Zeilinger K, Seehofer D, Damm G. Protocol for isolation of primary human hepatocytes and corresponding major populations of non-parenchymal liver cells. J Vis Exp 2016; (109): e53069.
[http://dx.doi.org/10.3791/53069] [PMID: 27077489]
[133]
Xiang C, Du Y, Meng G, et al. Long-term functional maintenance of primary human hepatocytes in vitro. Science 2019; 364(6438): 399-402.
[http://dx.doi.org/10.1126/science.aau7307] [PMID: 31023926]
[134]
Peng Z, Wu J, Hu S, et al. Requirments for primary human hepatocyte. Cell Prolif 2022; 55(4): e13147.
[http://dx.doi.org/10.1111/cpr.13147] [PMID: 34936148]
[135]
Zhang K, Zhang L, Liu W, et al. In vitro expansion of primary human hepatocytes with efficient liver repopulation capacity. Cell Stem Cell 2018; 23(6): 806-819.e4.
[http://dx.doi.org/10.1016/j.stem.2018.10.018] [PMID: 30416071]
[136]
Peng WC, Logan CY, Fish M, et al. Inflammatory cytokine TNFα promotes the long-term expansion of primary hepatocytes in 3D culture. Cell 2018; 175(6): 1607-1619.e15.
[http://dx.doi.org/10.1016/j.cell.2018.11.012] [PMID: 30500539]
[137]
Castell JV, Gómez-Lechón MJ. Liver cell culture techniques. Methods Mol Biol 2009; 481: 35-46.
[http://dx.doi.org/10.1007/978-1-59745-201-4_4] [PMID: 19096795]
[138]
Vosough M, Omidinia E, Kadivar M, et al. Generation of functional hepatocyte-like cells from human pluripotent stem cells in a scalable suspension culture. Stem Cells Dev 2013; 22(20): 2693-705.
[http://dx.doi.org/10.1089/scd.2013.0088] [PMID: 23731381]
[139]
Takayama K, Hagihara Y, Toba Y, Sekiguchi K, Sakurai F, Mizuguchi H. Enrichment of high-functioning human iPS cell-derived hepatocyte-like cells for pharmaceutical research. Biomaterials 2018; 161: 24-32.
[http://dx.doi.org/10.1016/j.biomaterials.2018.01.019] [PMID: 29421559]
[140]
Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 2004; 116(5): 639-48.
[http://dx.doi.org/10.1016/S0092-8674(04)00208-9] [PMID: 15006347]
[141]
Du C, Feng Y, Qiu D, et al. Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails. Stem Cell Res Ther 2018; 9(1): 58.
[http://dx.doi.org/10.1186/s13287-018-0794-4] [PMID: 29523187]
[142]
Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018; 93(1): 19-31.
[http://dx.doi.org/10.1002/cyto.a.23242] [PMID: 29072818]
[143]
Fu GB, Huang WJ, Zeng M, et al. Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens. Cell Res 2019; 29(1): 8-22.
[http://dx.doi.org/10.1038/s41422-018-0103-x] [PMID: 30361550]
[144]
Mohamadnejad M, Pournasr B, Bagheri M, et al. Transplantation of allogeneic bone marrow mesenchymal stromal cell-derived hepatocyte-like cells in homozygous familial hypercholesterolemia. Cytotherapy 2010; 12(4): 566-8.
[http://dx.doi.org/10.3109/14653240903511143] [PMID: 20078386]
[145]
Amer MEM, El-Sayed SZ, El-Kheir WA, et al. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol 2011; 23(10): 936-41.
[http://dx.doi.org/10.1097/MEG.0b013e3283488b00] [PMID: 21900788]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy