Display options
Share it on

Stem Cells Int. 2016;2016:4626073. doi: 10.1155/2016/4626073. Epub 2016 Feb 28.

3D Spheroid Culture Enhances the Expression of Antifibrotic Factors in Human Adipose-Derived MSCs and Improves Their Therapeutic Effects on Hepatic Fibrosis.

Stem cells international

Xuan Zhang, Ming-Gen Hu, Ke Pan, Chong-Hui Li, Rong Liu

Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese PLA General Hospital and Chinese PLA Medical College, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
  2. Department and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital and Chinese PLA Medical College, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.

PMID: 27022400 PMCID: PMC4789048 DOI: 10.1155/2016/4626073

Abstract

Three-dimensional (3D) cell culture has been reported to increase the therapeutic potentials of mesenchymal stem cells (MSCs). However, the action mechanisms of 3D MSCs vary greatly and are far from being thoroughly investigated. In this study, we aimed to investigate the therapeutic effects of 3D spheroids of human adipose-derived MSCs for hepatic fibrosis. Our results showed that 3D culture enhanced the expression of antifibrotic factors by MSCs, including insulin growth factor 1 (IGF-1), interleukin-6 (IL-6), and hepatocyte growth factor (HGF). In vitro studies indicated conditioned medium of 3D cultured MSCs protected hepatocytes from cell injury and apoptosis more effectively compared with 2D cultured cells. More importantly, when transplanted into model mice with hepatic fibrosis, 3D spheroids of MSCs were more beneficial in ameliorating hepatic fibrosis and improving liver function than 2D cultured cells. Therefore, the 3D culture strategy improved the therapeutic effects of MSCs and might be promising for treatment of hepatic fibrosis.

References

  1. J Transl Med. 2013 Mar 26;11:78 - PubMed
  2. Biomaterials. 2012 May;33(14):3673-81 - PubMed
  3. World J Gastroenterol. 2015 Jan 21;21(3):742-58 - PubMed
  4. BMC Gastroenterol. 2014 Nov 25;14:198 - PubMed
  5. Tissue Eng Part C Methods. 2010 Aug;16(4):735-49 - PubMed
  6. J Cell Biochem. 2009 Sep 1;108(1):145-55 - PubMed
  7. Differentiation. 2011 Jan;81(1):42-8 - PubMed
  8. Neurobiol Dis. 2012 Jun;46(3):635-45 - PubMed
  9. Chem Biol Interact. 2011 Sep 30;193(3):225-31 - PubMed
  10. Nat Med. 2005 Apr;11(4):367-8 - PubMed
  11. Mol Ther. 2011 Apr;19(4):741-50 - PubMed
  12. World J Gastroenterol. 2014 Jun 21;20(23):7260-76 - PubMed
  13. Stem Cells. 2009 Mar;27(3):724-32 - PubMed
  14. Stem Cells. 2007 Jul;25(7):1761-8 - PubMed
  15. Biomaterials. 2012 Apr;33(11):3093-106 - PubMed
  16. Biomaterials. 2009 May;30(14):2705-15 - PubMed
  17. Tissue Eng Part A. 2012 Jul;18(13-14):1352-64 - PubMed
  18. Clin Mol Hepatol. 2015 Jun;21(2):141-9 - PubMed
  19. Stem Cells Dev. 2013 Mar 15;22(6):845-54 - PubMed
  20. Circ Res. 2010 Mar 19;106(5):971-80 - PubMed
  21. Cell Biol Int. 2013 Jun;37(6):551-60 - PubMed
  22. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13724-9 - PubMed
  23. Stem Cells Int. 2016;2016:9062638 - PubMed
  24. Stem Cells. 2007 Aug;25(8):2118-27 - PubMed
  25. Biomol Ther (Seoul). 2012 Nov;20(6):556-61 - PubMed
  26. J Stem Cells Regen Med. 2012 Apr 14;8(1):28-34 - PubMed
  27. Biomed Res. 2010 Feb;31(1):27-34 - PubMed
  28. Hepatology. 2004 Dec;40(6):1304-11 - PubMed
  29. Biochem Biophys Res Commun. 2015 Jan 24;456(4):938-44 - PubMed
  30. Hepatology. 2008 May;47(5):1634-43 - PubMed
  31. J Thorac Cardiovasc Surg. 2008 Apr;135(4):799-808 - PubMed

Publication Types