Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
August-2016 Volume 38 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2016 Volume 38 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold

  • Authors:
    • Ji Bao
    • Qiong Wu
    • Yujia Wang
    • Yi Li
    • Li Li
    • Fei Chen
    • Xiujuan Wu
    • Mingjun Xie
    • Hong Bu
  • View Affiliations / Copyright

    Affiliations: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of General Surgery, Yibin City First People's Hospital, Yibin, Sichuan 644000, P.R. China
    Copyright: © Bao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 457-465
    |
    Published online on: June 14, 2016
       https://doi.org/10.3892/ijmm.2016.2638
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

In the present study, we aimed to determine whether the combination of aggregate culture and decellularized liver scaffolds (DLSs) promoted the hepatic differentiation of murine bone marrow-derived mesenchymal stem cells (BM-MSCs) into high yields of mature hepatocytes in vitro. Four culturing methods for differentiation [single cell (2D), spheroids (3D), 2D + DLS and 3D + DLS] were studied. To determine the differentiation stages of the MSCs, RT-qPCR of the hepatocyte genes, immunostaining of hepatocyte markers, and functional analyses were all performed. Compared with the other groups, hepatocyte-like cells which differentiated from BM‑MSC spheroids on extracellular matrix (ECM) exhibited more intensive staining of stored glycogen, an elevated level of urea biosynthesis and albumin secretion as well as the higher expression of hepatocyte-specific genes. Our results indicated that DLSs combined with spheroidal aggregate culture may be used as an effective method to facilitate the hepatic maturation of BM-MSCs and may have future applications in stem cell-based liver regenerative medicine.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Brown RS Jr: Live donors in liver transplantation. Gastroenterology. 134:1802–1813. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Vosough M, Moslem M, Pournasr B and Baharvand H: Cell-based therapeutics for liver disorders. Br Med Bull. 100:157–172. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Nussler A, Konig S, Ott M, Sokal E, Christ B, Thasler W, Brulport M, Gabelein G, Schormann W, Schulze M, et al: Present status and perspectives of cell-based therapies for liver diseases. J Hepatol. 45:144–159. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Zamule SM, Coslo DM, Chen F and Omiecinski CJ: Differentiation of human embryonic stem cells along a hepatic lineage. Chem Biol Interact. 190:62–72. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Shafritz DA, Oertel M, Menthena A, Nierhoff D and Dabeva MD: Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepatology. 43(Suppl 1): S89–S98. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Parekkadan B and Milwid JM: Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng. 12:87–117. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS and Verfaillie CM: Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest. 109:1291–1302. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Hong SH, Gang EJ, Jeong JA, Ahn C, Hwang SH, Yang IH, Park HK, Han H and Kim H: In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem Biophys Res Commun. 330:1153–1161. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Lange C, Bassler P, Lioznov MV, Bruns H, Kluth D, Zander AR and Fiegel HC: Hepatocytic gene expression in cultured rat mesenchymal stem cells. Transplant Proc. 37:276–279. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Chivu M, Dima SO, Stancu CI, Dobrea C, Uscatescu V, Necula LG, Bleotu C, Tanase C, Albulescu R, Ardeleanu C and Popescu I: In vitro hepatic differentiation of human bone marrow mesenchymal stem cells under differential exposure to liver-specific factors. Transl Res. 154:122–132. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Lee KD, Kuo TKC, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP and Lee OK: In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology. 40:1275–1284. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Tong JZ, Sarrazin S, Cassio D, Gauthier F and Alvarez F: Application of spheroid culture to human hepatocytes and maintenance of their differentiation. Biol Cell. 81:77–81. 1994. View Article : Google Scholar : PubMed/NCBI

13 

Li Y, Guo G, Li L, Chen F, Bao J, Shi YJ and Bu H: Three-dimensional spheroid culture of human umbilical cord mesenchymal stem cells promotes cell yield and stemness maintenance. Cell Tissue Res. 360:297–307. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Frith JE, Thomson B and Genever PG: Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng Part C Methods. 16:735–749. 2010. View Article : Google Scholar

15 

Subramanian K, Owens DJ, O'Brien TD, Verfaillie CM and Hu WS: Enhanced differentiation of adult bone marrow-derived stem cells to liver lineage in aggregate culture. Tissue Eng Part A. 17:2331–2341. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Subramanian K, Owens DJ, Raju R, Firpo M, O'Brien TD, Verfaillie CM and Hu WS: Spheroid culture for enhanced differentiation of human embryonic stem cells to hepatocyte-like cells. Stem Cells Dev. 23:124–131. 2014. View Article : Google Scholar :

17 

Takayama K, Kawabata K, Nagamoto Y, Kishimoto K, Tashiro K, Sakurai F, Tachibana M, Kanda K, Hayakawa T, Furue MK and Mizuguchi H: 3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing. Biomaterials. 34:1781–1789. 2013. View Article : Google Scholar

18 

Ng SL, Narayanan K, Gao S and Wan AC: Lineage restricted progenitors for the repopulation of decellularized heart. Biomaterials. 32:7571–7580. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Wang Y, Cui CB, Yamauchi M, Miguez P, Roach M, Malavarca R, Costello MJ, Cardinale V, Wauthier E, Barbier C, et al: Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatology. 53:293–305. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Ji R, Zhang N, You N, Li Q, Liu W, Jiang N, Liu J, Zhang H, Wang D, Tao K and Dou K: The differentiation of MSCs into functional hepatocyte-like cells in a liver biomatrix scaffold and their transplantation into liver-fibrotic mice. Biomaterials. 33:8995–9008. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Jiang WC, Cheng YH, Yen MH, Chang Y, Yang VW and Lee OK: Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering. Biomaterials. 35:3607–3617. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Wu Q, Bao J, Zhou YJ, Wang YJ, Du ZG, Shi YJ, Li L and Bu H: Optimizing perfusion-decellularization methods of porcine livers for clinical-scale whole-organ bioengineering. Biomed Res Int. 2015:7854742015. View Article : Google Scholar : PubMed/NCBI

23 

Bao J, Fisher JE, Lillegard JB, Wang W, Amiot B, Yu Y, Dietz AB, Nahmias Y and Nyberg SL: Serum-free medium and mesenchymal stromal cells enhance functionality and stabilize integrity of rat hepatocyte spheroids. Cell Transplant. 22:299–308. 2013. View Article : Google Scholar :

24 

Cheng NC, Wang S and Young TH: The influence of spheroid formation of human adipose-derived stem cells on chitosan films on stemness and differentiation capabilities. Biomaterials. 33:1748–1758. 2012. View Article : Google Scholar

25 

Glicklis R, Merchuk JC and Cohen S: Modeling mass transfer in hepatocyte spheroids via cell viability, spheroid size, and hepatocellular functions. Biotechnol Bioeng. 86:672–680. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Haouzi D, Baghdiguian S, Granier G, Travo P, Mangeat P and Hibner U: Three-dimensional polarization sensitizes hepatocytes to Fas/CD95 apoptotic signalling. J Cell Sci. 118:2763–2773. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Crapo PM, Gilbert TW and Badylak SF: An overview of tissue and whole organ decellularization processes. Biomaterials. 32:3233–3243. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Sabetkish S1, Kajbafzadeh AM, Sabetkish N, Khorramirouz R, Akbarzadeh A, Seyedian SL, Pasalar P, Orangian S, Beigi RS, Aryan Z, et al: Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix liver scaffolds. J Biomed Mater Res A. 103:1498–1508. 2015. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Bao J, Wu Q, Wang Y, Li Y, Li L, Chen F, Wu X, Xie M and Bu H: Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold. Int J Mol Med 38: 457-465, 2016.
APA
Bao, J., Wu, Q., Wang, Y., Li, Y., Li, L., Chen, F. ... Bu, H. (2016). Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold. International Journal of Molecular Medicine, 38, 457-465. https://doi.org/10.3892/ijmm.2016.2638
MLA
Bao, J., Wu, Q., Wang, Y., Li, Y., Li, L., Chen, F., Wu, X., Xie, M., Bu, H."Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold". International Journal of Molecular Medicine 38.2 (2016): 457-465.
Chicago
Bao, J., Wu, Q., Wang, Y., Li, Y., Li, L., Chen, F., Wu, X., Xie, M., Bu, H."Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold". International Journal of Molecular Medicine 38, no. 2 (2016): 457-465. https://doi.org/10.3892/ijmm.2016.2638
Copy and paste a formatted citation
x
Spandidos Publications style
Bao J, Wu Q, Wang Y, Li Y, Li L, Chen F, Wu X, Xie M and Bu H: Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold. Int J Mol Med 38: 457-465, 2016.
APA
Bao, J., Wu, Q., Wang, Y., Li, Y., Li, L., Chen, F. ... Bu, H. (2016). Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold. International Journal of Molecular Medicine, 38, 457-465. https://doi.org/10.3892/ijmm.2016.2638
MLA
Bao, J., Wu, Q., Wang, Y., Li, Y., Li, L., Chen, F., Wu, X., Xie, M., Bu, H."Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold". International Journal of Molecular Medicine 38.2 (2016): 457-465.
Chicago
Bao, J., Wu, Q., Wang, Y., Li, Y., Li, L., Chen, F., Wu, X., Xie, M., Bu, H."Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold". International Journal of Molecular Medicine 38, no. 2 (2016): 457-465. https://doi.org/10.3892/ijmm.2016.2638
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team