Skip to main content
Log in

Hepatic cell encapsulation using a decellularized liver scaffold

  • Original Article
  • Published:
Biomedical Engineering Letters Aims and scope Submit manuscript

Abstract

Purpose

To improve effect of liver disease treatment, tissue engineering approach such as direct hepatocyte injection has been investigated. Encapsulation, mixing cells and biomaterials to enclose cells within a biomaterial capsule, is commonly used to deliver cells into the body. Many kinds of biomaterials including natural and artificial materials have been used. The capsule must have biocompatibility and microstructure for cell culture, survival and proliferation as well as cell function and therapeutic effects. However, most biomaterials used for encapsulation have low biocompatibility, insufficient constituents and an unsuitable 3-dimensional structure. To solve these problems, we performed encapsulation using a decellularized liver scaffold (DCLS) with a native extracellular matrix (ECM) and natural porous microstructure including vasculature.

Methods

DCLS was prepared with 0.1% sodium dodecyl sulfate under agitation and 2 mm2 sized DCLS pieces were sterilized with peracetic acid (25.6 µl/10 ml) for 24 hours. Histological analysis showed that the DCLS had native ECM, liver specific major architecture and blood vessel structure but no cells. For cell encapsulation, hepG2 cells were injected into DCLS pieces with a syringe and cultured for 5 days.

Results

The cells survived and formed a cell mass with a liver ECM microstructure inside the DCLS capsules. The encapsulation status was similar to capsules formed by current encapsulation techniques.

Conclusions

DCLS can be used to make an encapsulation cell delivery system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Elizabeth J. Cellular transplantation for liver diseases. Gastroenterol Res. 2008; 1(1):8–13.

    MathSciNet  Google Scholar 

  2. Dixit V, Darvasi R, Arthur M, Brezina M, Lewin K, Gitnick G. Restoration of liver function in gunn rats without immunosuppression using transplanted microencapsulated hepatocytes. Hepatology. 1990; 12(6):1342–9.

    Article  Google Scholar 

  3. Zhao Y, Xu Y, Zhang B, Wu X, Xu F, Liang W, Du X, Li R. In vivo generation of thick, vascularized hepatic tissue from collagen hydrogel-based hepatic units. Tissue Eng Part C Methods. 2010; 16(4):653–9.

    Article  Google Scholar 

  4. Fan J, Shang Y, Yuan Y, Yang J. Preparation and characterization of chitosan/galactosylated hyaluronic acid scaffolds for primary hepatocytes culture. J Mater Sci Mater Med. 2010; 21(1):319–27.

    Article  Google Scholar 

  5. Semino CE, Merok JR, Crane GG, Panagiotakos G, Zhang S. Functional differentiation of hepatocyte-like spheroid structures from putative liver progenitor cells in three-dimensional peptide scaffolds. Differentiation. 2003; 71(4–5):262–70.

    Article  Google Scholar 

  6. Li RH. Materials for immunoisolated cell transplantation. Adv Drug Deliv Rev. 1998; 33(1–2):87–109.

    Article  Google Scholar 

  7. Rokstad AM, Lacík I, de Vos P, Strand BL. Advances in biocompatibility and physico-chemical characterization of microspheres for cell encapsulation. Adv Drug Deliv Rev. 2014; 67–68:111–30.

    Article  Google Scholar 

  8. Ratner BD. The biocompatibility manifesto: biocompatibility for the twenty-first century. J Cardiovasc Transl Res. 2011; 4(5):523–7.

    Article  Google Scholar 

  9. Turner AE, Flynn LE. Design and characterization of tissuespecific extracellular matrix-derived microcarriers. Tissue Eng Part C Methods. 2012; 18(3):186–97.

    Article  Google Scholar 

  10. Sgroi A, Mai G, Morel P, Baertschiger RM, Gonelle-Gispert C, Serre-Beinier V, Buhler LH. Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration. Cell Transplant. 2011; 20(11–12):1791–803.

    Article  Google Scholar 

  11. Liu ZC, Chang TM. Intrasplenic transplantation of bioencapsulated mesenchymal stem cells improves the recovery rates of 90% partial hepatectomized rats. Stem Cells Int. 2012; 2012:697094.

  12. Zanin MP, Pettingill LN, Harvey AR, Emerich DF, Thanos CG, Shepherd RK. The development of encapsulated cell technologies as therapies for neurological and sensory diseases. J Control Release. 2012; 160(1):3–13.

    Article  Google Scholar 

  13. Harm S, Stroble K, Hartmann J, Falkenhagen D. Alginateencapsulated human hepatoma C3A cells for use in a bioartificial liver device - the hybrid-MDS. Int J Artif Organs. 2009; 32(11):769–78.

    Google Scholar 

  14. Paul A, Chen G, Khan A, Rao VT, Shum-Tim D, Prakash S. Genipin-cross-linked microencapsulated human adipose stem cells augment transplant retention resulting in attenuation of chronically infarcted rat heart fibrosis and cardiac dysfunction. Cell Transplant. 2012; 21(12):2735–51.

    Article  Google Scholar 

  15. Blasi P, Giovagnoli S, Schoubben A, Ricci M, Rossi C, Luca G, Basta G, Calafiore R. Preparation and in vitro and in vivo characterization of composite microcapsules for cell encapsulation. Int J Pharm. 2006; 324(1):27–36.

    Article  Google Scholar 

  16. Hammond JS, Gilbert TW, Howard D, Zaitoun A, Michalopoulos G, Shakesheff KM, Beckingham IJ, Badylak SF. Scaffolds containing growth factors and extracellular matrix induce hepatocyte proliferation and cell migration in normal and regenerating rat liver. J Hepatol. 2011; 54(2):279–87.

    Article  Google Scholar 

  17. Oe S, Fukunaka Y, Hirose T, Yamaoka Y, Tabata Y. A trial on regeneration therapy of rat liver cirrhosis by controlled release of hepatocyte growth factor. J Control Release. 2003; 88(2):193–200.

    Article  Google Scholar 

  18. Davis MW, Vacanti JP. Toward development of an implantable tissue engineered liver. Biomaterials. 1996; 17(3):365–72.

    Article  Google Scholar 

  19. Freimark D, Pino-Grace P, Pohl S, Weber C, Wallrapp C, Geigle P, Pörtner R, Czermak P. Use of encapsulated stem cells toovercome the bottleneck of cell availability for cell therapy approaches. Transfus Med Hemother. 2010; 37(2):66–73.

    Article  Google Scholar 

  20. Fiegel HC, Kaufmann PM, Bruns H, Kluth D, Horch RE, Vacanti JP, Kneser U. Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory. J Cell Mol Med. 2008; 12(1):56–66.

    Article  Google Scholar 

  21. Ji R, Zhang N, You N, Li Q, Liu W, Jiang N, Liu J, Zhang H, Wang D, Tao K, Dou K. The differentiation of MSCs into functional hepatocyte-like cells in a liver biomatrix scaffold and their transplantation into liver-fibrotic mice. Biomaterials. 2012; 33(35):8995–9008.

    Article  Google Scholar 

  22. de Vos P, Lazarjani HA, Poncelet D, Faas MM. Polymers in cell encapsulation from an enveloped cell perspective. Adv Drug Deliv Rev. 2014; 67–8:15–34.

    Article  Google Scholar 

  23. Wang Y, Cui CB, Yamauchi M, Miguez P, Roach M, Malavarca R, Costello MJ, Cardinale V, Wauthier E, Barbier C, Gerber DA, Alvaro D, Reid LM. Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatology. 2011; 53(1):293–305.

    Article  Google Scholar 

  24. Sasisekharan R, Raman R, Prabhakar V. Glycomics approach to structure-function relationships of glycosaminoglycans. Annu Rev Biomed Eng. 2008; 8:181–231.

    Article  Google Scholar 

  25. Uygun BE, Soto-Gutierrez A, Yagi H, zamis ML, Guzzardi MA, Shulman C, Milwid J, Kobayashi N, Tilles A, Berthiaume F, Hertl M, Nahmias Y, Yarmush ML, Uygun K. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010; 16(7):814–20.

    Article  Google Scholar 

  26. Bao J, Shi Y, Sun H, Yin X, Yang R, Li L, Chen X, Bu H. Construction of a portal implantable functional tissue-engineered liver using perfusion-decellularized matrix and hepatocytes in rats. Cell Transplant. 2011; 20(5):753–66.

    Article  Google Scholar 

  27. Shirakigawa N, Takei T, Ijima H. Base structure consisting of an endothelialized vascular-tree network and hepatocytes for whole liver engineering. J Biosci Bioeng. 2013; 116(6):740–5.

    Article  Google Scholar 

  28. Hussein KH, Park KM, Teotia PK, Yang JW, Kim HM, Hong SH, Yang SR, Park IC, Park SM, Woo HM. Fabrication of a biodegradable xenoantigen-free rat liver scaffold for potential drug screening applications. Transplant Proc. 2013; 45(8):3092–6.

    Article  Google Scholar 

  29. Rokstad AM, Strand B, Rian K, Steinkjer B, Kulseng B, Skjåk-Braek G, Espevik T. Evaluation of different types of alginate microcapsules as bioreactors for producing endostatin. Cell Transplant. 2003; 12(4):351–64.

    Article  Google Scholar 

  30. Kedem A, Perets A, Gamlieli-Bonshtein I, Dvir-Ginzberg M, Mizrahi S, Cohen S. Vascular endothelial growth factorreleasing scaffolds enhance vascularization and engraftment of hepatocytes transplanted on liver lobes. Tissue Eng. 2005; 11(5- 6):715–22.

    Article  Google Scholar 

  31. Madden LR, Mortisen DJ, Sussman EM, Dupras SK, Fugate JA, Cuy JL, Hauch KD, Laflamme MA, Murry CE, Ratner BD. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc Natl Acad Sci USA. 2010; 107(34):15211–6.

    Article  Google Scholar 

  32. Bryers JD, Giachelli CM, Ratner BD. Engineering biomaterialsto integrate and heal: the biocompatibility paradigm shifts. Biotechnol Bioeng. 2012; 109(8):1898–911.

    Article  Google Scholar 

  33. Griffith CK, Miller C, Sainson RC, Calvert JW, Jeon NL, Hughes CC, George SC. Diffusion limits of an in vitro thick prevascularized tissue. Tissue Eng. 2005; 11(1–2):257–66.

    Article  Google Scholar 

  34. Michalopoulos GK. Liver regeneration. J Cell Physiol. 2007; 213(2):286–300.

    Article  Google Scholar 

  35. Roos F, Ryan AM, Chamow SM, Bennett GL, Schwall RH. Induction of liver growth in normal mice by infusion of hepatocyte growth factor/scatter factor. Am J Physiol. 1995;268(2 Pt 1): G380–6.

  36. Webber E, Godowski PJ, Fausto N. In vivo response of hepatocytes to growth factors requires an initial priming stimulus. Hepatology. 1994; 19(2):489–97.

    Article  Google Scholar 

  37. Ishii T, Sato M, Sudo K, Suzuki M, Nakai H, Hishida T, Niwa T, Umezu K, Yuasa S. Hepatocyte growth factor stimulates liver regeneration and elevates blood protein levels in normal and partially hepatectomized rats. J Biochem. 1995; 117(5):1105–12.

    Google Scholar 

  38. Liu ML, Mars WM, Zarnegar R, Michalopoulos GK. Collagenase pretreatment and the mitogenic effects of hepatocyte growth factor and transforming growth factor in adult liver. Hepatology. 1994; 19(6):1521–7.

    Article  Google Scholar 

  39. Fujiwara K, Nagoshi S, Ohno A, Hirata K, Ohta Y, Mochida S, Tomiya T, Higashio K, Kurokawa K. Stimulation of liver growth by exogenous human hepatocyte growth factor in norma and partially hepatectomised rats. Hepatology. 1993; 18(6):1443–9.

    Article  Google Scholar 

  40. Patijn GA, Lieber A, Schowalter DB, Schwall R, Kay MA. Hepatocte growth factor induces hepatocyte proliferation in vivo and allows for efficient retro-viral mediated gene transfer in mice. Hepatology. 1998; 28(3):707–16.

    Article  Google Scholar 

  41. Fausto N. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology. 2004; 39(6):1477–87.

    Article  Google Scholar 

  42. Sellaro TL, Ravindra AK, Stolz DB, Badylak SF. Maintenance of hepatic sinusoidal endothelial cell phenotype in vitro using organ-specific extracellular matrix scaffolds. Tissue Eng. 2007; 13(9):2301–10.

    Article  Google Scholar 

  43. Skardal A, Smith L, Bharadwaj S, Atala A, Soker S, Zhang Y. Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function. Biomaterials. 2012; 33(18):4565–75.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heung Myong Woo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghim, J.H., Hussein, K.H., Park, KM. et al. Hepatic cell encapsulation using a decellularized liver scaffold. Biomed. Eng. Lett. 5, 58–64 (2015). https://doi.org/10.1007/s13534-015-0176-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13534-015-0176-0

Keywords

Navigation