Hepatocyte Transplantation pp 259-271 | Cite as
Microencapsulation of Hepatocytes and Mesenchymal Stem Cells for Therapeutic Applications
Abstract
Encapsulated hepatocyte transplantation and encapsulated mesenchymal stem cell transplantation are newly developed potential treatments for acute and chronic liver diseases, respectively. Cells are microencapsulated in biocompatible semipermeable alginate-based hydrogels. Microspheres protect cells against antibodies and immune cells, while allowing nutrients, small/medium size proteins and drugs to diffuse inside and outside the polymer matrix. Microencapsulated cells are assessed in vitro and designed for experimental transplantation and for future clinical applications.
Here, we describe the protocol for microencapsulation of hepatocytes and mesenchymal stem cells within hybrid poly(ethylene glycol)-alginate hydrogels.
Key words
Encapsulation Capsule Microspheres Microbeads Alginate Hydrogels Hepatocyte Mesenchymal stem cells Liver failure Hepatitis Fibrosis CirrhosisNotes
Acknowledgments
This work was supported by Swiss National Science Foundation (SNSF) grant 205322 130572/1 and 205321 141286/1, the Insuleman Foundation, the Foundation Privée des HUG, and the Geneva University Hospital and Medical School.
References
- 1.Meier RP, Navarro-Alvarez N, Morel P et al (2015) Current status of hepatocyte xenotransplantation. Int J Surg 23:273–279CrossRefPubMedGoogle Scholar
- 2.Rokstad AM, Brekke OL, Steinkjer B et al (2011) Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model. Acta Biomater 7:2566–2578CrossRefPubMedGoogle Scholar
- 3.Rokstad AM, Brekke OL, Steinkjer B et al (2013) The induction of cytokines by polycation containing microspheres by a complement dependent mechanism. Biomaterials 34:621–630CrossRefPubMedGoogle Scholar
- 4.Meier RP, Seebach JD, Morel P et al (2014) Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow. PLoS One 9:e91268CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Lavallard V, Armanet M, Parnaud G et al (2015) Cell rearrangement in transplanted human islets. FASEB J 30:748–760CrossRefPubMedGoogle Scholar
- 6.Mahou R, Meier R, Bühler L et al (2014) Alginate-poly(ethylene glycol) hybrid microspheres for primary cell microencapsulation. Materials 7:275–286CrossRefGoogle Scholar
- 7.Mahou R, Wandrey C (2010) Alginate-poly(ethylene glycol) hybrid microspheres with adjustable physical properties. Macromolecules 43:1371–1378CrossRefGoogle Scholar
- 8.Mahou R, Kolláriková G, Gonelle-Gispert C et al (2013) Combined electrostatic and covalent polymer networks for cell microencapsulation. Macromolecular Symposia 329:49–57CrossRefGoogle Scholar
- 9.Mei J, Sgroi A, Mai G et al (2009) Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice. Cell Transplant 18:101–110CrossRefPubMedGoogle Scholar
- 10.Sgroi A, Mai G, Morel P et al (2011) Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration. Cell Transplant 20:1791–1803CrossRefPubMedGoogle Scholar
- 11.Meier RP, Mahou R, Morel P et al (2015) Microencapsulated human mesenchymal stem cells decrease liver fibrosis in mice. J Hepatol 62:634–641CrossRefPubMedGoogle Scholar
- 12.Meier RP, Muller YD, Morel P et al (2013) Transplantation of mesenchymal stem cells for the treatment of liver diseases, is there enough evidence? Stem Cell Res 11:1348–1364CrossRefPubMedGoogle Scholar
- 13.Hengstler JG, Brulport M, Schormann W et al (2005) Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin Drug Metab Toxicol 1:61–74CrossRefPubMedGoogle Scholar