Abstract
The increased incidence of end-stage liver disease (ESLD) causes a major burden on the global health system and population health. Liver transplantation (LT) is one of the most effective treatments for ESLD patients, but its practice is extensively hampered by the scarcity of liver donors, the limited number of transplantation centers, the complexity of the procedure, and postoperative complication. In parallel, vast growing advances in cellular biology and biotechnology have opened new alternatives in clinics, including the transplantation of adult stem cells for chronic diseases such as ESLD. Numerous types of stem cells, such as mesenchymal stem cells, hematopoietic stem cells, endothelial progenitor cells, and other cells, obtained from bone marrow, umbilical cord, adipose tissue, or peripheral blood had been isolated and given to ESLD patients all over the world. Many clinical data had demonstrated promising results, indicating its potential. However, conclusive protocol and agreement on adult stem cell definition and transplantation method are still lacking, and thus further research must still be conducted.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- BM:
-
Bone marrow
- EPC:
-
Endothelial progenitor cells
- ESC:
-
Embryonic stem cells
- ESLD:
-
End-stage liver disease
- HBV:
-
Hepatitis B virus
- HCC:
-
Hepatitis C virus
- HCC:
-
Hepatocellular carcinoma
- HLO:
-
Human liver organoid
- HSC:
-
Hematopoietic stem cells
- iPSC:
-
Induced pluripotent stem cells
- LPC:
-
Liver progenitor cells
- LT:
-
Liver transplantation
- MELD:
-
Model for End-Stage Liver Disease
- MSC:
-
Mesenchymal stromal/stem cells
- PHH:
-
Primary human hepatocytes
References
Amer M-EM, El-Sayed SZ, El-Kheir WA, Gabr H, Gomaa AA, El-Noomani N, Hegazy M (2011) Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol 23(10):936–941. https://doi.org/10.1097/MEG.0b013e3283488b00
Amin MA, Sabry D, Rashed LA, Aref WM, el-Ghobary MA, Farhan MS, Fouad HA, Youssef YA-A (2013) Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study. Clin Transpl 27(4):607–612. https://doi.org/10.1111/ctr.12179
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967. https://doi.org/10.1126/science.275.5302.964
Asrani SK, Devarbhavi H, Eaton J, Kamath PS (2019) Burden of liver diseases in the world. J Hepatol 70(1):151–171. https://doi.org/10.1016/j.jhep.2018.09.014
Au KP, Chan ACY (2019) Is living donor liver transplantation justified in high model for end-stage liver disease candidates (35+)? Curr Opin Organ Transplant 24(5):637–643. https://doi.org/10.1097/MOT.0000000000000689
Berger I, Ahmad A, Bansal A, Kapoor T, Sipp D, Rasko JEJ (2016) Global distribution of businesses marketing stem cell-based interventions. Cell Stem Cell 19(2):158–162. https://doi.org/10.1016/j.stem.2016.07.015
Blum B, Benvenisty N (2008) The tumorigenicity of human embryonic stem cells. Adv Cancer Res 100:133–158. https://doi.org/10.1016/S0065-230X(08)00005-5
Bracha P, Moore NA, Ciulla TA (2017) Induced pluripotent stem cell-based therapy for age-related macular degeneration. Expert Opin Biol Ther 17(9):1113–1126. https://doi.org/10.1080/14712598.2017.1346079
Bucher NLR, Swaffield MN (1964) The rate of incorporation of labeled thymidine into the deoxyribonucleic acid of regenerating rat liver in relation to the amount of liver excised. Cancer Res 24(9):1611–1625
Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9(5):641–650. https://doi.org/10.1002/jor.1100090504
Caplan AI (2010) What’s in a name? Tissue Eng Part A 16(8):2415–2417. https://doi.org/10.1089/ten.TEA.2010.0216
Caplan AI (2017) Mesenchymal stem cells: time to change the name! Stem Cells Transl Med 6(6):1445–1451. https://doi.org/10.1002/sctm.17-0051
Catani L, Sollazzo D, Bianchi E, Ciciarello M, Antoniani C, Foscoli L, Caraceni P, Giannone FA, Baldassarre M, Giordano R, Montemurro T, Montelatici E, D’Errico A, Andreone P, Giudice V, Curti A, Manfredini R, Lemoli RM (2017) Molecular and functional characterization of CD133+ stem/progenitor cells infused in patients with end-stage liver disease reveals their interplay with stromal liver cells. Cytotherapy 19(12):1447–1461. https://doi.org/10.1016/j.jcyt.2017.08.001
Chang M, Bogacheva MS, Lou Y-R (2021) Challenges for the applications of human pluripotent stem cell-derived liver organoids. Front Cell Dev Biol 9:748576. https://doi.org/10.3389/fcell.2021.748576
Chen Y-F, Tseng C-Y, Wang H-W, Kuo H-C, Yang VW, Lee OK (2012) Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. Hepatology 55(4):1193–1203. https://doi.org/10.1002/hep.24790
Choudhary NS, Saraf N, Dhampalwar S, Saigal S, Gautam D, Rastogi A, Bhangui P, Srinivasan T, Rastogi V, Mehrotra S, Soin AS (2022) Poor outcomes after recidivism in living donor liver transplantation for alcohol-related liver disease. J Clin Exp Hepatol 12(1):37–42. https://doi.org/10.1016/j.jceh.2021.04.005
Corti S, Locatelli F, Donadoni C, Strazzer S, Salani S, Del Bo R, Caccialanza M, Bresolin N, Scarlato G, Comi GP (2002) Neuroectodermal and microglial differentiation of bone marrow cells in the mouse spinal cord and sensory ganglia. J Neurosci Res 70(6):721–733. https://doi.org/10.1002/jnr.10455
D’Avola D, Fernández-Ruiz V, Carmona-Torre F, Méndez M, Pérez-Calvo J, Prósper F, Andreu E, Herrero JI, Iñarrairaegui M, Fuertes C, Bilbao JI, Sangro B, Prieto J, Quiroga J (2017) Phase 1–2 pilot clinical trial in patients with decompensated liver cirrhosis treated with bone marrow-derived endothelial progenitor cells. Transl Res 188:80–91.e2. https://doi.org/10.1016/j.trsl.2016.02.009
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8(4):315–317. https://doi.org/10.1080/14653240600855905
El-Ansary M, Abdel-Aziz I, Mogawer S, Abdel-Hamid S, Hammam O, Teaema S, Wahdan M (2012) Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis. Stem Cell Rev Rep 8(3):972–981. https://doi.org/10.1007/s12015-011-9322-y
European Association for the Study of the Liver (2018) EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol 69(2):406–460. https://doi.org/10.1016/j.jhep.2018.03.024
Feng S, Bucuvalas J (2017) Tolerance after liver transplantation: where are we? Liver Transplant 23(12):1601–1614. https://doi.org/10.1002/lt.24845
Fitzpatrick E, Mitry RR, Dhawan A (2009) Human hepatocyte transplantation: state of the art. J Intern Med 266(4):339–357. https://doi.org/10.1111/j.1365-2796.2009.02152.x
Fricker ZP, Serper M (2019) Current knowledge, barriers to implementation, and future directions in palliative Care for end-Stage Liver Disease. Liver Transplant 25(5):787–796. https://doi.org/10.1002/lt.25434
Fujikawa T, Oh S-H, Pi L, Hatch HM, Shupe T, Petersen BE (2005) Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am J Pathol 166(6):1781–1791. https://doi.org/10.1016/S0002-9440(10)62488-1
Giancotti A, D’Ambrosio V, Corno S, Pajno C, Carpino G, Amato G, Vena F, Mondo A, Spiniello L, Monti M, Muzii L, Bosco D, Gaudio E, Alvaro D, Cardinale V (2022) Current protocols and clinical efficacy of human fetal liver cell therapy in patients with liver disease: a literature review. Cytotherapy 24(4):376–384. https://doi.org/10.1016/j.jcyt.2021.10.012
Godoy P, Hewitt NJ, Albrecht U, Andersen ME, Ansari N, Bhattacharya S, Bode JG, Bolleyn J, Borner C, Böttger J, Braeuning A, Budinsky RA, Burkhardt B, Cameron NR, Camussi G, Cho C-S, Choi Y-J, Craig Rowlands J, Dahmen U, Damm G, Dirsch O, Donato MT, Dong J, Dooley S, Drasdo D, Eakins R, Ferreira KS, Fonsato V, Fraczek J, Gebhardt R, Gibson A, Glanemann M, Goldring CEP, Gómez-Lechón MJ, Groothuis GMM, Gustavsson L, Guyot C, Hallifax D, Hammad S, Hayward A, Häussinger D, Hellerbrand C, Hewitt P, Hoehme S, Holzhütter H-G, Houston JB, Hrach J, Ito K, Jaeschke H, Keitel V, Kelm JM, Kevin Park B, Kordes C, Kullak-Ublick GA, LeCluyse EL, Lu P, Luebke-Wheeler J, Lutz A, Maltman DJ, Matz-Soja M, McMullen P, Merfort I, Messner S, Meyer C, Mwinyi J, Naisbitt DJ, Nussler AK, Olinga P, Pampaloni F, Pi J, Pluta L, Przyborski SA, Ramachandran A, Rogiers V, Rowe C, Schelcher C, Schmich K, Schwarz M, Singh B, Stelzer EHK, Stieger B, Stöber R, Sugiyama Y, Tetta C, Thasler WE, Vanhaecke T, Vinken M, Weiss TS, Widera A, Woods CG, Xu JJ, Yarborough KM, Hengstler JG (2013) 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 87(8):1315–1530. https://doi.org/10.1007/s00204-013-1078-5
Gordon MY, Levicar N, Pai M, Bachellier P, Dimarakis I, Al-Allaf F, M’Hamdi H, Thalji T, Welsh JP, Marley SB, Davies J, Dazzi F, Marelli-Berg F, Tait P, Playford R, Jiao L, Jensen S, Nicholls JP, Ayav A, Nohandani M, Farzaneh F, Gaken J, Dodge R, Alison M, Apperley JF, Lechler R, Habib NA (2006) Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells 24(7):1822–1830. https://doi.org/10.1634/stemcells.2005-0629
Gridelli B, Vizzini G, Pietrosi G, Luca A, Spada M, Gruttadauria S, Cintorino D, Amico G, Chinnici C, Miki T, Schmelzer E, Conaldi PG, Triolo F, Gerlach JC (2012) Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation. Liver Transplant 18(2):226–237. https://doi.org/10.1002/lt.22322
Gurdon JB (1962) The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10:622–640
Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401(6751):390–394. https://doi.org/10.1038/43919
Haep N, Florentino RM, Squires JE, Bell A, Soto-Gutierrez A (2021) The inside-out of end-stage liver disease: hepatocytes are the keystone. Semin Liver Dis 41(2):213–224. https://doi.org/10.1055/s-0041-1725023
Haideri SS, McKinnon AC, Taylor AH, Kirkwood P, Starkey Lewis PJ, O’Duibhir E, Vernay B, Forbes S, Forrester LM (2017) Injection of embryonic stem cell derived macrophages ameliorates fibrosis in a murine model of liver injury. NPJ Regen Med 2:14. https://doi.org/10.1038/s41536-017-0017-0
Hannoun Z, Steichen C, Dianat N, Weber A, Dubart-Kupperschmitt A (2016) The potential of induced pluripotent stem cell derived hepatocytes. J Hepatol 65(1):182–199. https://doi.org/10.1016/j.jhep.2016.02.025
Harries L, Gwiasda J, Qu Z, Schrem H, Krauth C, Amelung VE (2019) Potential savings in the treatment pathway of liver transplantation: an inter-sectorial analysis of cost-rising factors. Eur J Health Econ 20(2):281–301. https://doi.org/10.1007/s10198-018-0994-y
Hentze H, Soong PL, Wang ST, Phillips BW, Putti TC, Dunn NR (2009) Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. Stem Cell Res 2(3):198–210. https://doi.org/10.1016/j.scr.2009.02.002
Heo J, Factor VM, Uren T, Takahama Y, Lee J-S, Major M, Feinstone SM, Thorgeirsson SS (2006) Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver. Hepatology 44(6):1478–1486. https://doi.org/10.1002/hep.21441
Hermerén G (2014) Human stem-cell research in gastroenterology: experimental treatment, tourism and biobanking. Best Pract Res Clin Gastroenterol 28(2):257–268. https://doi.org/10.1016/j.bpg.2014.02.002
Herrero JI (2012) Screening of de novo tumors after liver transplantation. J Gastroenterol Hepatol 27(6):1011–1016. https://doi.org/10.1111/j.1440-1746.2011.06981.x
Hess DC, Abe T, Hill WD, Studdard AM, Carothers J, Masuya M, Fleming PA, Drake CJ, Ogawa M (2004) Hematopoietic origin of microglial and perivascular cells in brain. Exp Neurol 186(2):134–144. https://doi.org/10.1016/j.expneurol.2003.11.005
Higgins G (1931) Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202
Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A, International Society for Cellular Therapy (2005) Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy 7(5):393–395. https://doi.org/10.1080/14653240500319234
Hu H, Gehart H, Artegiani B, LÖpez-Iglesias C, Dekkers F, Basak O, van Es J, Chuva de Sousa Lopes SM, Begthel H, Korving J, van den Born M, Zou C, Quirk C, Chiriboga L, Rice CM, Ma S, Rios A, Peters PJ, de Jong YP, Clevers H (2018) Long-term expansion of functional mouse and human hepatocytes as 3D organoids. Cell 175(6):1591–1606.e19. https://doi.org/10.1016/j.cell.2018.11.013
Hu C, Zhao L, Li L (2019) Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases. Stem Cell Res Ther 10(1):199. https://doi.org/10.1186/s13287-019-1310-1
Jang Y-Y, Collector MI, Baylin SB, Diehl AM, Sharkis SJ (2004) Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol 6(6):532–539. https://doi.org/10.1038/ncb1132
Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D’Amico G, Dickson ER, Kim WR (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33(2):464–470. https://doi.org/10.1053/jhep.2001.22172
Kantarcıoğlu M, Demirci H, Avcu F, Karslıoğlu Y, Babayiğit MA, Karaman B, Öztürk K, Gürel H, Akdoğan Kayhan M, Kaçar S, Kubar A, Öksüzoğlu G, Ural AU, Bağcı S (2015) Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis. Turk J Gastroenterol 26(3):244–250. https://doi.org/10.5152/tjg.2015.0074
Keighron C, Lyons CJ, Creane M, O’Brien T, Liew A (2018) Recent advances in endothelial progenitor cells toward their use in clinical translation. Front Med 5:354. https://doi.org/10.3389/fmed.2018.00354
Khan AA, Shaik MV, Parveen N, Rajendraprasad A, Aleem MA, Habeeb MA, Srinivas G, Raj TA, Tiwari SK, Kumaresan K, Venkateswarlu J, Pande G, Habibullah CM (2010) Human fetal liver-derived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis. Cell Transplant 19(4):409–418. https://doi.org/10.3727/096368910X498241
Kharaziha P, Hellström PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M (2009) Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol 21(10):1199–1205. https://doi.org/10.1097/MEG.0b013e32832a1f6c
Kim WR, Mannalithara A, Heimbach JK, Kamath PS, Asrani SK, Biggins SW, Wood NL, Gentry SE, Kwong AJ (2021) MELD 3.0: the model for end-stage liver disease updated for the modern era. Gastroenterology 161(6):1887–1895.e4. https://doi.org/10.1053/j.gastro.2021.08.050
Lan L, Liu R, Qin L-Y, Cheng P, Liu B-W, Zhang B-Y, Ding S-Z, Li X-L (2018) Transplantation of bone marrow-derived endothelial progenitor cells and hepatocyte stem cells from liver fibrosis rats ameliorates liver fibrosis. World J Gastroenterol 24(2):237–247. https://doi.org/10.3748/wjg.v24.i2.237
Lee CA, Sinha S, Fitzpatrick E, Dhawan A (2018) Hepatocyte transplantation and advancements in alternative cell sources for liver-based regenerative medicine. J Mol Med 96(6):469–481. https://doi.org/10.1007/s00109-018-1638-5
Li Y-H, Xu Y, Wu H-M, Yang J, Yang L-H, Yue-Meng W (2016) Umbilical cord-derived mesenchymal stem cell transplantation in hepatitis B virus related acute-on-chronic liver failure treated with plasma exchange and Entecavir: a 24-month prospective study. Stem Cell Rev Rep 12(6):645–653. https://doi.org/10.1007/s12015-016-9683-3
Lian G, Wang C, Teng C, Zhang C, Du L, Zhong Q, Miao C, Ding M, Deng H (2006) Failure of hepatocyte marker-expressing hematopoietic progenitor cells to efficiently convert into hepatocytes in vitro. Exp Hematol 34(3):348–358. https://doi.org/10.1016/j.exphem.2005.12.004
Liang L, Ma T, Chen W, Hu J, Bai X, Li J, Liang T (2009) Therapeutic potential and related signal pathway of adipose-derived stem cell transplantation for rat liver injury. Hepatol Res 39(8):822–832. https://doi.org/10.1111/j.1872-034X.2009.00506.x
Liang J, Zhang H, Zhao C, Wang D, Ma X, Zhao S, Wang S, Niu L, Sun L (2017) Effects of allogeneic mesenchymal stem cell transplantation in the treatment of liver cirrhosis caused by autoimmune diseases. Int J Rheum Dis 20(9):1219–1226. https://doi.org/10.1111/1756-185X.13015
Libbrecht L, Roskams T (2002) Hepatic progenitor cells in human liver diseases. Semin Cell Dev Biol 13(6):389–396. https://doi.org/10.1016/s1084952102001258
Lin B-L, Chen J-F, Qiu W-H, Wang K-W, Xie D-Y, Chen X-Y, Liu Q-L, Peng L, Li J-G, Mei Y-Y, Weng W-Z, Peng Y-W, Cao H-J, Xie J-Q, Xie S-B, Xiang AP, Gao Z-L (2017) Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial. Hepatology 66(1):209–219. https://doi.org/10.1002/hep.29189
Lorenzini S, Gitto S, Grandini E, Andreone P, Bernardi M (2008) Stem cells for end stage liver disease: how far have we got? World J Gastroenterol 14(29):4593–4599. https://doi.org/10.3748/wjg.14.4593
Luo X, Leanza J, Massie AB, Garonzik-Wang JM, Haugen CE, Gentry SE, Ottmann SE, Segev DL (2018) MELD as a metric for survival benefit of liver transplantation. Am J Transplant 18(5):1231–1237. https://doi.org/10.1111/ajt.14660
Manzia TM, Angelico R, Gazia C, Lenci I, Milana M, Ademoyero OT, Pedini D, Toti L, Spada M, Tisone G, Baiocchi L (2019) De novo malignancies after liver transplantation: the effect of immunosuppression-personal data and review of literature. World J Gastroenterol 25(35):5356–5375. https://doi.org/10.3748/wjg.v25.i35.5356
Martins AM, Vunjak-Novakovic G, Reis RL (2014) The current status of iPS cells in cardiac research and their potential for tissue engineering and regenerative medicine. Stem Cell Rev Rep 10(2):177–190. https://doi.org/10.1007/s12015-013-9487-7
Masson S, Harrison DJ, Plevris JN, Newsome PN (2004) Potential of hematopoietic stem cell therapy in hepatology: a critical review. Stem Cells 22(6):897–907. https://doi.org/10.1634/stemcells.22-6-897
Medina RJ, Barber CL, Sabatier F, Dignat-George F, Melero-Martin JM, Khosrotehrani K, Ohneda O, Randi AM, Chan JKY, Yamaguchi T, Van Hinsbergh VWM, Yoder MC, Stitt AW (2017) Endothelial progenitors: a consensus statement on nomenclature. Stem Cells Transl Med 6(5):1316–1320. https://doi.org/10.1002/sctm.16-0360
Mohamadnejad M, Alimoghaddam K, Bagheri M, Ashrafi M, Abdollahzadeh L, Akhlaghpoor S, Bashtar M, Ghavamzadeh A, Malekzadeh R (2013) Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. Liver Int 33(10):1490–1496. https://doi.org/10.1111/liv.12228
Moriya K, Yoshikawa M, Ouji Y, Saito K, Nishiofuku M, Matsuda R, Ishizaka S, Fukui H (2008) Embryonic stem cells reduce liver fibrosis in CCl4-treated mice. Int J Exp Pathol 89(6):401–409. https://doi.org/10.1111/j.1365-2613.2008.00607.x
Mountford JC (2008) Human embryonic stem cells: origins, characteristics and potential for regenerative therapy. Transfus Med 18(1):1–12. https://doi.org/10.1111/j.1365-3148.2007.00807.x
Nagai S, Chau LC, Schilke RE, Safwan M, Rizzari M, Collins K, Yoshida A, Abouljoud MS, Moonka D (2018) Effects of allocating livers for transplantation based on model for end-stage liver disease–sodium scores on patient outcomes. Gastroenterology 155(5):1451–1462.e3. https://doi.org/10.1053/j.gastro.2018.07.025
Nhung TH, Nam NH, Nguyen NTK, Nghia H, Van Thanh N, Ngoc PK, Van Pham P (2015) A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells. Vitro Cell Dev Biol Anim 51(10):1085–1092. https://doi.org/10.1007/s11626-015-9939-2
Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701–705. https://doi.org/10.1038/35070587
Pan X-N, Zheng L-Q, Lai X-H (2014) Bone marrow-derived mesenchymal stem cell therapy for decompensated liver cirrhosis: a meta-analysis. World J Gastroenterol 20(38):14051–14057. https://doi.org/10.3748/wjg.v20.i38.14051
Peng L, Xie D, Lin B-L, Liu J, Zhu H, Xie C, Zheng Y, Gao Z (2011) Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology 54(3):820–828. https://doi.org/10.1002/hep.24434
Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP (1999) Bone marrow as a potential source of hepatic oval cells. Science 284(5417):1168–1170. https://doi.org/10.1126/science.284.5417.1168
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147. https://doi.org/10.1126/science.284.5411.143
Prasain N, Meador JL, Yoder MC (2012) Phenotypic and functional characterization of endothelial Colony forming cells derived from human umbilical cord blood. JoVE J Vis Exp 62:e3872. https://doi.org/10.3791/3872
Qin M, Guan X, Zhang Y, Shen B, Liu F, Zhang Q, Ma Y, Jiang Y (2018) Evaluation of ex vivo produced endothelial progenitor cells for autologous transplantation in primates. Stem Cell Res Ther 9(1):14. https://doi.org/10.1186/s13287-018-0769-5
Reza HA, Ryo O, Takebe T (2021) Organoid transplant approaches for the liver. Transpl Int. https://doi.org/10.1111/tri.14128
Sacchetti B, Funari A, Remoli C, Giannicola G, Kogler G, Liedtke S, Cossu G, Serafini M, Sampaolesi M, Tagliafico E, Tenedini E, Saggio I, Robey PG, Riminucci M, Bianco P (2016) No identical “mesenchymal stem cells” at different times and sites: human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels. Stem Cell Rep 6(6):897–913. https://doi.org/10.1016/j.stemcr.2016.05.011
Safarikia S, Carpino G, Overi D, Cardinale V, Venere R, Franchitto A, Onori P, Alvaro D, Gaudio E (2020) Distinct EpCAM-positive stem cell niches are engaged in chronic and neoplastic liver diseases. Front Med 7:479. https://doi.org/10.3389/fmed.2020.00479
Sakai Y, Fukunishi S, Takamura M, Inoue O, Takashima S, Usui S, Seki A, Nasti A, Ho TTB, Kawaguchi K, Asai A, Tsuchimoto Y, Yamashita T, Yamashita T, Mizukoshi E, Honda M, Imai Y, Yoshimura K, Murayama T, Wada T, Harada K, Higuchi K, Kaneko S (2020) Regenerative therapy for liver cirrhosis based on intrahepatic arterial infusion of autologous subcutaneous adipose tissue-derived regenerative (stem) cells: protocol for a confirmatory multicenter uncontrolled clinical trial. JMIR Res Protoc 9(3):e17904. https://doi.org/10.2196/17904
Sakai Y, Fukunishi S, Takamura M, Kawaguchi K, Inoue O, Usui S, Takashima S, Seki A, Asai A, Tsuchimoto Y, Nasti A, Bich Ho TT, Imai Y, Yoshimura K, Murayama T, Yamashita T, Arai K, Yamashita T, Mizukoshi E, Honda M, Wada T, Harada K, Higuchi K, Kaneko S (2021) Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy. Regen Ther 18:97–101. https://doi.org/10.1016/j.reth.2021.04.003
Sakamoto M, Nakamura T, Torimura T, Iwamoto H, Masuda H, Koga H, Abe M, Hashimoto O, Ueno T, Sata M (2013) Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model. J Gastroenterol Hepatol 28(1):168–178. https://doi.org/10.1111/j.1440-1746.2012.07238.x
Salama H, Zekri A-RN, Bahnassy AA, Medhat E, Halim HA, Ahmed OS, Mohamed G, Al Alim SA, Sherif GM (2010) Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. World J Gastroenterol 16(42):5297–5305. https://doi.org/10.3748/wjg.v16.i42.5297
Salama H, Zekri A-RN, Medhat E, Al Alim SA, Ahmed OS, Bahnassy AA, Lotfy MM, Ahmed R, Musa S (2014) Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease. Stem Cell Res Ther 5(3):70. https://doi.org/10.1186/scrt459
Schacher FC, Martins Pezzi da Silva A, Silla LM d R, Álvares-da-Silva MR (2021) Bone marrow mesenchymal stem cells in acute-on-chronic liver failure grades 2 and 3: a phase I-II randomized clinical trial. Can J Gastroenterol Hepatol 2021:3662776. https://doi.org/10.1155/2021/3662776
Semeraro R, Cardinale V, Carpino G, Gentile R, Napoli C, Venere R, Gatto M, Brunelli R, Gaudio E, Alvaro D (2013) The fetal liver as cell source for the regenerative medicine of liver and pancreas. Ann Transl Med 1(2):13. https://doi.org/10.3978/j.issn.2305-5839.2012.10.02
Sharma AD, Cantz T, Vogel A, Schambach A, Haridass D, Iken M, Bleidissel M, Manns MP, Schöler HR, Ott M (2008) Murine embryonic stem cell-derived hepatic progenitor cells engraft in recipient livers with limited capacity of liver tissue formation. Cell Transplant 17(3):313–323. https://doi.org/10.3727/096368908784153896
Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Zhang A, Shi J, Chen L, Lv S, He W, Geng H, Jin L, Liu Z, Wang F-S (2012) Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med 1(10):725–731. https://doi.org/10.5966/sctm.2012-0034
Sipp D (2017) The malignant niche: safe spaces for toxic stem cell marketing. Npj Regen Med 2(1):1–4. https://doi.org/10.1038/s41536-017-0036-x
Sipp D, Robey PG, Turner L (2018) Clear up this stem-cell mess. Nature 561(7724):455–457. https://doi.org/10.1038/d41586-018-06756-9
Sison-Young RL, Lauschke VM, Johann E, Alexandre E, Antherieu S, Aerts H, Gerets HHJ, Labbe G, Hoët D, Dorau M, Schofield CA, Lovatt CA, Holder JC, Stahl SH, Richert L, Kitteringham NR, Jones RP, Elmasry M, Weaver RJ, Hewitt PG, Ingelman-Sundberg M, Goldring CE, Park BK (2017) A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity. Arch Toxicol 91(3):1385–1400. https://doi.org/10.1007/s00204-016-1745-4
Song Z, Cai J, Liu Y, Zhao D, Yong J, Duo S, Song X, Guo Y, Zhao Y, Qin H, Yin X, Wu C, Che J, Lu S, Ding M, Deng H (2009) Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res 19(11):1233–1242. https://doi.org/10.1038/cr.2009.107
Stachelscheid H, Wulf-Goldenberg A, Eckert K, Jensen J, Edsbagge J, Björquist P, Rivero M, Strehl R, Jozefczuk J, Prigione A, Adjaye J, Urbaniak T, Bussmann P, Zeilinger K, Gerlach JC (2013) Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors. J Tissue Eng Regen Med 7(9):729–741. https://doi.org/10.1002/term.1467
Sumide K, Matsuoka Y, Kawamura H, Nakatsuka R, Fujioka T, Asano H, Takihara Y, Sonoda Y (2018) A revised road map for the commitment of human cord blood CD34-negative hematopoietic stem cells. Nat Commun 9(1):2202. https://doi.org/10.1038/s41467-018-04441-z
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. https://doi.org/10.1016/j.cell.2006.07.024
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. https://doi.org/10.1016/j.cell.2007.11.019
Tarlow BD, Pelz C, Naugler WE, Wakefield L, Wilson EM, Finegold MJ, Grompe M (2014) Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell 15(5):605–618. https://doi.org/10.1016/j.stem.2014.09.008
Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I (2006) Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells 24(10):2292–2298. https://doi.org/10.1634/stemcells.2005-0542
Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L, Kumar A, Crawford JM (1999) The canals of Hering and hepatic stem cells in humans. Hepatology 30(6):1425–1433. https://doi.org/10.1002/hep.510300614
Thorgeirsson SS, Grisham JW (2006) Hematopoietic cells as hepatocyte stem cells: a critical review of the evidence. Hepatology 43(1):2–8. https://doi.org/10.1002/hep.21015
Tsuchida T, Murata S, Matsuki K, Mori A, Matsuo M, Mikami S, Okamoto S, Ueno Y, Tadokoro T, Zheng Y-W, Taniguchi H (2019) The regenerative effect of portal vein injection of liver organoids by Retrorsine/partial hepatectomy in rats. Int J Mol Sci 21(1):E178. https://doi.org/10.3390/ijms21010178
Tsujimoto H, Osafune K (2021) Current status and future directions of clinical applications using iPS cells-focus on Japan. FEBS J. https://doi.org/10.1111/febs.16162
Wang J, Kimura T, Asada R, Harada S, Yokota S, Kawamoto Y, Fujimura Y, Tsuji T, Ikehara S, Sonoda Y (2003) SCID-repopulating cell activity of human cord blood-derived CD34- cells assured by intra-bone marrow injection. Blood 101(8):2924–2931. https://doi.org/10.1182/blood-2002-09-2782
Wiesner R, Edwards E, Freeman R, Harper A, Kim R, Kamath P, Kremers W, Lake J, Howard T, Merion RM, Wolfe RA, Krom R, United Network for Organ Sharing Liver Disease Severity Score Committee (2003) Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 124(1):91–96. https://doi.org/10.1053/gast.2003.50016
Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KHS (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385(6619):810–813. https://doi.org/10.1038/385810a0
Wilson HV (1907) A new method by which sponges may be artificially reared. Science 25(649):912–915. https://doi.org/10.1126/science.25.649.912
Xiang Z, Hua M, Hao Z, Biao H, Zhu C, Zhai G, Wu J (2022) The roles of mesenchymal stem cells in gastrointestinal cancers. Front Immunol 13:844001. https://doi.org/10.3389/fimmu.2022.844001
Yanagida A, Ito K, Chikada H, Nakauchi H, Kamiya A (2013) An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential. PLoS One 8(7):e67541. https://doi.org/10.1371/journal.pone.0067541
Zanjani ED, Almeida-Porada G, Livingston AG, Flake AW, Ogawa M (1998) Human bone marrow CD34- cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp Hematol 26(4):353–360
Zekri A-RN, Salama H, Medhat E, Musa S, Abdel-Haleem H, Ahmed OS, Khedr HAH, Lotfy MM, Zachariah KS, Bahnassy AA (2015) The impact of repeated autologous infusion of haematopoietic stem cells in patients with liver insufficiency. Stem Cell Res Ther 6:118. https://doi.org/10.1186/s13287-015-0106-1
Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, Chen L, Lv S, Li Y, Yu S, Geng H, Jin L, Lau GKK, Wang F-S (2012) Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol 27(Suppl 2):112–120. https://doi.org/10.1111/j.1440-1746.2011.07024.x
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Sukowati, C.H.C., Tiribelli, C. (2022). Adult Stem Cell Therapy as Regenerative Medicine for End-Stage Liver Disease. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 17. Advances in Experimental Medicine and Biology(), vol 1401. Springer, Cham. https://doi.org/10.1007/5584_2022_719
Download citation
DOI: https://doi.org/10.1007/5584_2022_719
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-20513-2
Online ISBN: 978-3-031-20514-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)