Rapid and High-efficiency Generation of Mature Functional Hepatocyte-like Cells from Adipose-derived Stem Cells by a Three-step Protocol

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2015 Oct 7

PMID 26438426

Citations 12

Authors

Fen Xu

Junli Liu

Jie Deng

Xiaolei Chen

Yuan Wang

Pengchao Xu

Lin Cheng

Yanli Fu

Fuyi Cheng

Yunqi Yao

Yujing Zhang

Meijuan Huang

Dechao Yu

Yuquan Wei

Hongxin Deng

Affiliations

Soon will be listed here.

Abstract

The generation of functional hepatocytes is a major challenge for regenerative medicine and drug discovery. Here we show a method that facilitates generation of induced functional hepatocytes (iHeps) from adipose-derived stem cells (ADSCs) within 9 days. iHeps express hepatocytic gene programs and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity. Upon transplantation into mice with carbon tetrachloride (CCl4)-induced acute fulminant liver failure, iHeps restore the liver function and prolong survival. The work could contribute to the development of alternative strategies to obtain nonhepatic cell-derived mature hepatocytes with potential for biomedical and pharmaceutical applications.

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References

Gimble J, Guilak F, Bunnell B . Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells. Stem Cell Res Ther. 2010; 1(2):19. PMC: 2905095. DOI: 10.1186/scrt19. View

Aurich H, Sgodda M, Kaltwasser P, Vetter M, Weise A, Liehr T . Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut. 2008; 58(4):570-81. DOI: 10.1136/gut.2008.154880. View

Feng N, Han Q, Li J, Wang S, Li H, Yao X . Generation of highly purified neural stem cells from human adipose-derived mesenchymal stem cells by Sox1 activation. Stem Cells Dev. 2013; 23(5):515-29. PMC: 3929335. DOI: 10.1089/scd.2013.0263. View

Huang P, Zhang L, Gao Y, He Z, Yao D, Wu Z . Direct reprogramming of human fibroblasts to functional and expandable hepatocytes. Cell Stem Cell. 2014; 14(3):370-84. DOI: 10.1016/j.stem.2014.01.003. View

Subramanian K, Owens D, Raju R, Firpo M, OBrien T, Verfaillie C . Spheroid culture for enhanced differentiation of human embryonic stem cells to hepatocyte-like cells. Stem Cells Dev. 2013; 23(2):124-31. PMC: 3887452. DOI: 10.1089/scd.2013.0097. View

Zhu L, Qu X, Li J, Lin R, Liao L, Wang J . Stepwise differentiation of human adipose-derived mesenchymal stem cells toward definitive endoderm and pancreatic progenitor cells by mimicking pancreatic development in vivo. Stem Cells Dev. 2012; 22(10):1576-87. DOI: 10.1089/scd.2012.0148. View

Han S, Coh Y, Ahn J, Jang G, Yum S, Kang S . Enhanced hepatogenic transdifferentiation of human adipose tissue mesenchymal stem cells by gene engineering with Oct4 and Sox2. PLoS One. 2015; 10(3):e0108874. PMC: 4376765. DOI: 10.1371/journal.pone.0108874. View

Okura H, Komoda H, Saga A, Kakuta-Yamamoto A, Hamada Y, Fumimoto Y . Properties of hepatocyte-like cell clusters from human adipose tissue-derived mesenchymal stem cells. Tissue Eng Part C Methods. 2009; 16(4):761-70. DOI: 10.1089/ten.TEC.2009.0208. View

Takayama K, Inamura M, Kawabata K, Katayama K, Higuchi M, Tashiro K . Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4α transduction. Mol Ther. 2011; 20(1):127-37. PMC: 3255576. DOI: 10.1038/mt.2011.234. View

10.

Gimble J, Bunnell B, Guilak F . Human adipose-derived cells: an update on the transition to clinical translation. Regen Med. 2012; 7(2):225-35. PMC: 3321837. DOI: 10.2217/rme.11.119. View

11.

Schwartz R, Fleming H, Khetani S, Bhatia S . Pluripotent stem cell-derived hepatocyte-like cells. Biotechnol Adv. 2014; 32(2):504-13. PMC: 4043206. DOI: 10.1016/j.biotechadv.2014.01.003. View

12.

Li W, Jiang K, Ding S . Concise review: A chemical approach to control cell fate and function. Stem Cells. 2011; 30(1):61-8. DOI: 10.1002/stem.768. View

13.

Volarevic V, Nurkovic J, Arsenijevic N, Stojkovic M . Concise review: Therapeutic potential of mesenchymal stem cells for the treatment of acute liver failure and cirrhosis. Stem Cells. 2014; 32(11):2818-23. DOI: 10.1002/stem.1818. View

14.

Xu D, Nishimura T, Zheng M, Wu M, Su H, Sato N . Enabling autologous human liver regeneration with differentiated adipocyte stem cells. Cell Transplant. 2013; 23(12):1573-84. DOI: 10.3727/096368913X673432. View

15.

Bunnell B, Flaat M, Gagliardi C, Patel B, Ripoll C . Adipose-derived stem cells: isolation, expansion and differentiation. Methods. 2008; 45(2):115-20. PMC: 3668445. DOI: 10.1016/j.ymeth.2008.03.006. View

16.

Zuk P, Zhu M, Mizuno H, Huang J, Futrell J, Katz A . Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001; 7(2):211-28. DOI: 10.1089/107632701300062859. View

17.

Yang Q, Du X, Fang Z, Xiong W, Li G, Liao H . Effect of calcitonin gene-related peptide on the neurogenesis of rat adipose-derived stem cells in vitro. PLoS One. 2014; 9(1):e86334. PMC: 3897681. DOI: 10.1371/journal.pone.0086334. View

18.

Gimble J, Katz A, Bunnell B . Adipose-derived stem cells for regenerative medicine. Circ Res. 2007; 100(9):1249-60. PMC: 5679280. DOI: 10.1161/01.RES.0000265074.83288.09. View

19.

Yin L, Zhu Y, Yang J, Ni Y, Zhou Z, Chen Y . Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro. Mol Med Rep. 2014; 11(3):1722-32. PMC: 4270341. DOI: 10.3892/mmr.2014.2935. View

20.

Kokai L, Marra K, Rubin J . Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Transl Res. 2013; 163(4):399-408. DOI: 10.1016/j.trsl.2013.11.009. View