Abstract
Decellularized tissues (DETs) have been attracting great attention as scaffolds for tissue-engineering approaches. Recently, some studies have reported that decellularized liver tissues (DLT) can provide an excellent environment for the hepatocytic differentiation of hepatic stem/progenitor cells that were already committed to the hepatocyte lineage. However, the effects of DLT on the hepatocytic differentiation of induced pluripotent stem cells (iPSs) have not yet been established. Here we studied the hepatocytic differentiation of iPSs on DLT and decellularized heart tissues (DHT) in order to determine the tissue-specific effects of DETs on iPSs differentiation. Our results showed that DLTs led to higher gene expression levels of forkhead box A2 (a marker of endoderm) and CCAAT/enhancer binding protein-α (master transcription factor to hepatocyte differentiation), alpha-fetoprotein (a marker of fetal hepatocyte,), and albumin (a marker of fetal and mature hepatocyte) of iPSs than on DHTs. Furthermore, gene expression levels of tyrosine aminotransferase (a marker of mature hepatocyte) were higher on DLT than that on DHT, and immunocytochemical analysis and ELISA assay showed that albumin secretion level of iPSs on DLT was higher than that on DHT. Our study demonstrated that the use of DLTs led to mature hepatocytic differentiation levels of iPSs compared to DHTs, which provides a better niche for iPSs cell engineering and enables the preparation of useful mature cells for regenerative therapy.
Similar content being viewed by others
References
Fox IJ, Roy-Chowdhury J. Hepatocyte transplantation. J Hepatol. 2004;40:878–86.
Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. 1998;338:1422–6.
Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–21.
Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials. 2006;27:3675–83.
Vesely I. Heart valve tissue engineering. Circ Res. 2005;97:743–55.
Crapo PM, Medberry CJ, Reing JE, Tottey S, van der Merwe Y, Jones KE, et al. Biologic scaffolds composed of central nervous system extracellular matrix. Biomaterials. 2012;33:3539–47.
Neubauer D, Graham JB, Muir D. Chondroitinase treatment increases the effective length of acellular nerve grafts. Exp Neurol. 2007;207:163–70.
Hashimoto Y, Funamoto S, Sasaki S, Honda T, Hattori S, Nam K, et al. Preparation and characterization of decellularized cornea using high-hydrostatic pressurization for corneal tissue engineering. Biomaterials. 2010;31:3941–8.
Fu Y, Fan X, Chen P, Shao C, Lu W. Reconstruction of a tissue-engineered cornea with porcine corneal acellular matrix as the scaffold. Cells, Tissues, Organs. 2010;191:193–202.
Eberli D, Rodriguez S, Atala A, Yoo JJ. In vivo evaluation of acellular human dermis for abdominal wall repair. J Biomed Mater Res, Part A. 2010;93:1527–38.
Ng SL, Narayanan K, Gao S, Wan AC. Lineage restricted progenitors for the repopulation of decellularized heart. Biomaterials. 2011;32:7571–80.
Lu TY, Lin B, Kim J, Sullivan M, Tobita K, Salama G, et al. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat Commun. 2013;4:2307.
Higuchi S, Lin Q, Wang J, Lim TK, Joshi SB, Anand GS, et al. Heart extracellular matrix supports cardiomyocyte differentiation of mouse embryonic stem cells. J Biosci Bioeng. 2013;115:320–5.
Uygun BE, Soto-Gutierrez A, Yagi H, Izamis ML, Guzzardi MA, Shulman C, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010;16:814–20.
Soto-Gutierrez A, Zhang L, Medberry C, Fukumitsu K, Faulk D, Jiang H, et al. A whole-organ regenerative medicine approach for liver replacement. Tissue Eng Part C, Methods. 2011;17:677–86.
Wang Y, Cui CB, Yamauchi M, Miguez P, Roach M, Malavarca R, et al. Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatology (Baltimore, MD). 2011;53:293–305.
Barakat O, Abbasi S, Rodriguez G, Rios J, Wood RP, Ozaki C, et al. Use of decellularized porcine liver for engineering humanized liver organ. J Surg Res. 2012;173:e11–25.
Wang X, Cui J, Zhang BQ, Zhang H, Bi Y, Kang Q, et al. Decellularized liver scaffolds effectively support the proliferation and differentiation of mouse fetal hepatic progenitors. J Biomed Mater Res, Part A. 2014;102:1017–25.
Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008;26:101–6.
Zhang Q, Yang Y, Zhang J, Wang GY, Liu W, Qiu DB, et al. Efficient derivation of functional hepatocytes from mouse induced pluripotent stem cells by a combination of cytokines and sodium butyrate. Chin Med J. 2011;124:3786–93.
Shiojiri N. Enzymo- and immunocytochemical analyses of the differentiation of liver cells in the prenatal mouse. J Embryol Exp Morphol. 1981;62:139–52.
Jones EA, Clement-Jones M, James OF, Wilson DI. Differences between human and mouse alpha-fetoprotein expression during early development. J Anat. 2001;198:555–9.
Sellem CH, Frain M, Erdos T, Sala-Trepat JM. Differential expression of albumin and alpha-fetoprotein genes in fetal tissues of mouse and rat. Dev Biol. 1984;102:51–60.
Shiojiri N, Takeshita K, Yamasaki H, Iwata T. Suppression of C/EBP alpha expression in biliary cell differentiation from hepatoblasts during mouse liver development. J Hepatol. 2004;41:790–8.
Greengard O. Enzymic differentiation in mammalian liver injection of fetal rats with hormones causes the premature formation of liver enzymes. Science (New York, NY). 1969;163:891–5.
Shelly LL, Tynan W, Schmid W, Schutz G, Yeoh GC. Hepatocyte differentiation in vitro: initiation of tyrosine aminotransferase expression in cultured fetal rat hepatocytes. J Cell Biol. 1989;109:3403–10.
DeQuach JA, Yuan SH, Goldstein LS, Christman KL. Decellularized porcine brain matrix for cell culture and tissue engineering scaffolds. Tissue Eng Part A. 2011;17:2583–92.
Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126:677–89.
Shamis Y, Hasson E, Soroker A, Bassat E, Shimoni Y, Ziv T, et al. Organ-specific scaffolds for in vitro expansion, differentiation, and organization of primary lung cells. Tissue Eng Part C, Methods. 2011;17:861–70.
Han S, Bourdon A, Hamou W, Dziedzic N, Goldman O, Gouon-Evans V. Generation of functional hepatic cells from pluripotent stem cells. J Stem Cell Res Ther. 2012;Suppl 10:1–7.
Macchiarini P, Jungebluth P, Go T, Asnaghi MA, Rees LE, Cogan TA, et al. Clinical transplantation of a tissue-engineered airway. Lancet (London, England). 2008;372:2023–30.
Bao J, Shi Y, Sun H, Yin X, Yang R, Li L, et al. Construction of a portal implantable functional tissue-engineered liver using perfusion-decellularized matrix and hepatocytes in rats. Cell Transplant. 2011;20:753–66.
Gonfiotti A, Jaus MO, Barale D, Baiguera S, Comin C, Lavorini F, et al. The first tissue-engineered airway transplantation: 5-year follow-up results. Lancet (London, England). 2014;383:238–44.
Mahara A, Somekawa S, Kobayashi N, Hirano Y, Kimura Y, Fujisato T, et al. Tissue-engineered acellular small diameter long-bypass grafts with neointima-inducing activity. Biomaterials. 2015;58:54–62.
Hashimoto Y, Funamoto S, Kimura T, Nam K, Fujisato T, Kishida A. The effect of decellularized bone/bone marrow produced by high-hydrostatic pressurization on the osteogenic differentiation of mesenchymal stem cells. Biomaterials. 2011;32:7060–7.
Liem PH, Morimoto N, Mahara A, Jinno C, Shima K, Ogino S, et al. Preparation of Inactivated Human Skin Using High Hydrostatic Pressurization for Full-Thickness Skin Reconstruction. PLoS ONE. 2015;10:e0133979.
Acknowledgments
This research was supported by the intramural research fund from National Cerebral and Cardiovascular Center (25-2-2) and by a grant-in aid for scientific research (exploratory research) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Part of this research was supported by the S-innovation Research Program for the “Development of biofunctional materials for realization of innovative medicine,” Japan Agency for Medical Research and Development (AMED).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
We have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Hirata, M., Yamaoka, T. Hepatocytic differentiation of iPS cells on decellularized liver tissue. J Artif Organs 20, 318–325 (2017). https://doi.org/10.1007/s10047-017-0977-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10047-017-0977-2