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Cited by 30Tissue Engineering and Regenerative MedicineHydrogels: synthesis, properties, applications3D Printing in Biomedical Research

Intact extracellular matrix component promotes maintenance of liver-specific functions and larger aggregates formation of primary rat hepatocytes

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Bual, Ronald P., Ijima, Hiroyuki·2019·Regenerative Therapy
DOI 10.1016/j.reth.2019.08.006PMC PMC6813644
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Abstract

. However, whether an intact composition of ECM is required for an efficient ECM-based substrate design remains to be clarified. In this study, two L-ECM hydrogels, namely L-ECM I and L-ECM II, were prepared by pepsin solubilization at 4 °C and 25 °C, respectively. The solubility at 4 °C was 50% whereas that at 25 °C was 95%, thus indicating well-preserved L-ECM. Analysis confirmed higher ECM protein components (especially collagen) in L-ECM II, along with denser fiber network and larger fiber diameter. L-ECM II gel exhibited high compression strength and suitable viscoelastic properties. Furthermore, hepatocytes in L-ECM II showed higher expression of liver-specific functions in 3D culture and wider spread while maintaining the cell-cell contacts in 2D culture. Therefore, an intact L-ECM is important to realize effective substrates for liver tissue engineering.

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  1. [2]Badylak S.F. The extracellular matrix as a scaffold for tissue reconstruction Semin Cell Dev Biol 13 2002 377 383 12324220
  2. [3]Freytes D.O. Martin J. Velankar S.S. Lee A.S. Badylak S.F. Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix Biomaterials 29 2008 1630 1637 18201760
  3. [4]Frantz C. Stewart K.M. Weaver V.M. The extracellular matrix at a glance J Cell Sci 123 2010 4195 4200 21123617 PMC2995612
  4. [5]Gilbert T.W. Strategies for tissue and organ decellularization J Cell Biochem 113 2012 2217 2222 22415903
  5. [6]Crapo P.M. Gilbert T.W. Badylak D.V.M. An overview of tissue and whole organ decellularization process Biomaterials 32 2011 3233 3243 21296410 PMC3084613
  6. [7]Sabetkish S. Kajbafzadeh A.M. Sabetkish N. Khorramirouz R. Akbarzadeh A. Seyedian S.L. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix liver scaffolds J Biomed Mater Res Part A 103 2015 1498 1508 25045886
  7. [10]Shirakigawa N. Takei T. Ijima H. Base structure consisting of an endothelialized vascular-tree network and hepatocytes for whole liver engineering J Biosci Bioeng 116 2013 740 745 23770123
  8. [11]Ijima H. Nakamura S. Bual R. Shirakigawa N. Tanoue S. Physical properties of the extracellular matrix of decellularized porcine liver Gels 4 2018 1 15 PMC6209282 30674815
  9. [12]Sellaro T.L. Ranade A. Faulk D.M. McCabe G.P. Dorko K. Badylak S.F. Maintenance of human hepatocyte function in vitro by liver-derived extracellular matrix gels Tissue Eng Part A 16 2010 1075 1082 19845461 PMC2863084
  10. [13]Lee J.S. Shin J. Park H.M. Kim Y.G. Kim B.G. Oh J.W. Liver extracellular matrix providing dual functions of two-dimensional substrate coating and three-dimensional injectable hydrogel platform for liver tissue engineering Biomacromolecules 15 2014 206 218 24350561
  11. [14]Nakamura S. Ijima H. Solubilized matrix derived from decellularized liver as a growth factor-immobilizable scaffold for hepatocyte culture J Biosci Bioeng 116 2013 746 753 23810667
  12. [16]Wang Y. Kim M.H. Shirahama H. Lee J.H. Ng S.S. Glenn J.S. ECM proteins in a microporous scaffold influence hepatocyte morphology, function, and gene expression Sci Rep 6 2016 1 13 27897167 PMC5126637
  13. [17]Seglen P.O. Chapter 4 preparation of isolated rat liver cells Methods Cell Biol 13 1976 29 83 177845
  14. [19]Lang R. Stern M.M. Smith L. Liu Y. Bharadwaj S. Liu G. Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix Biomaterials 32 2011 7042 7052 21723601
  15. [22]Sato K. Ebihara T. Adachi E. Kawashima S. Hattori S. Irie S. Possible involvement of aminotelopeptide in self-assembly and thermal stability of collagen I as revealed by its removal with proteases J Biol Chem 275 2000 25870 25875 10851240
  16. [23]Brown B. Lindberg K. Reing J. Stolz D.B. Badylak S.F. The basement membrane component of biologic scaffolds derived from extracellular matrix Tissue Eng 12 2006 519 526 16579685
  17. [24]Shoulder RTR M.D. Collagen structure and stability Annu Rev Biochem 2009 929 958 [COLLAGEN] 19344236 PMC2846778
  18. [25]Yu H. Mouw J.K. Weaver V.M. Forcing form and function: biomechanical regulation of tumor evolution Trends Cell Biol 21 2011 47 56 Forcing 20870407 PMC3014395
  19. [26]Lu P. Takai K. Weaver V.M. Werb Z. Extracellular Matrix degradation and remodeling in development and disease Cold Spring Harb Perspect Biol 3 2011 1 24 PMC3225943 21917992
  20. [27]Daley W.P. Peters S.B. Larsen M. Extracellular matrix dynamics in development and regenerative medicine J Cell Sci 121 2008 255 264 18216330
  21. [28]Wells R.G. The role of matrix stiffness in regulating cell behavior Hepatology 47 2008 1394 1400 18307210
  22. [29]Kular J.K. Basu S. Sharma R.I. The extracellular matrix: structure, composition, age-related differences, tools for analysis and applications for tissue engineering J Tissue Eng 5 2014 1 17 PMC4883592 25610589
  23. [30]Le Thi P. Lee Y. Nguyen D.H. Park K.D. In situ forming gelatin hydrogels by dual-enzymatic cross-linking for enhanced tissue adhesiveness J Mater Chem B 5 2017 757 764 32263844
  24. [32]Kharkar P.M. Kiick K.L. Kloxin A.M. Designing degradable hydrogels for orthogonal control of cell microenvironments Chem Soc Rev 42 2013 7335 7372 23609001 PMC3762890
  25. [33]Lin C.C. Anseth K.S. PEG hydrogels for the controlled release of biomolecules in regenerative medicine Pharm Res 26 2009 631 643 19089601 PMC5892412
  26. [34]Tibbitt M.W. Anseth K.S. Hydrogels as extracellular matrix mimics for 3D cell culture Biotechnol Bioeng 103 2009 655 663 19472329 PMC2997742
  27. [35]Yamamoto J. Udono M. Miura S. Sekiya S. Suzuki A. Cell aggregation culture induces functional differentiation of induced hepatocyte-like cells through activation of Hippo signaling Cell Rep 25 2018 183 198 30282027
  28. [36]Stamenkovic I. Extracellular matrix remodelling: the role of matrix metalloproteinases J Pathol 200 2003 448 464 12845612
  29. [37]Rubin K. Staffan J. Hook M. Obrink B. Substrate adhesion OF rat hepatocytes: on the role of fibronectin in cell spreading Exp Cell Res 135 1981 127 135 7286075
  30. [38]Sánchez A. Álvarez A.M. Pagan R. Roncero C. Vilaró S. Benito M. Fibronectin regulates morphology, cell organization and gene expression of rat fetal hepatocytes in primary culture J Hepatol 32 2000 242 250 10707864
  31. [39]Sawada N. Tomomura A. Sattler C.A. Sattler G.L. Kleinman H.K. Pitot H.C. Effects of extracellular matrix components on the growth and differentiation of cultured rat hepatocytes In Vitro Cell Dev Biol 23 1987 267 273 2883170
  32. [40]Johansson S. Hook M. Substrate adhesion of rat hepatocytes: mechanism of attachment to collagen substrates J Cell Biol 98 1984 810 817 6321520 PMC2113136
  33. [41]Sawada N. Tomomura A. Sattlet A. Sattler G.L. Kleinman H.K. Pitot H.C. Extracellular matrix components influence DNA synthesis of rat hepatocytes in primary Culture 167 1986 458 470 3490392
  34. [42]Coronado R.E. Somaraki-Cormier M. Natesan S. Christy R.J. Ong J.L. Halff G.A. Decellularization and solubilization of porcine liver for use as a substrate for porcine hepatocyte culture Cell Transplant 26 2017 1840 1854 29390876 PMC5802637
  35. [43]Hammond J.S. Gilbert T.W. Howard D. Zaitoun A. Michalopoulos G. Shakesheff K.M. Scaffolds containing growth factors and extracellular matrix induce hepatocyte proliferation and cell migration in normal and regenerating rat liver J Hepatol 54 2011 279 287 21126791
  36. [44]Hou Y Te Ijima H. Takei T. Kawakami K. Growth factor/heparin-immobilized collagen gel system enhances viability of transplanted hepatocytes and induces angiogenesis J Biosci Bioeng 112 2011 265 272 21640648
  37. [45]Whitaker M.J. Quirk R.A. Howdle S.M. Shakesheff K.M. Growth factor release from tissue engineering scaffolds J Pharm Pharmacol 53 2001 1427 1437 11732745
  38. [46]Michalopoulos G.K. Zarnegar R. Hepatocyte growth factor Hepatology 15 1992 149 155 1530787
  39. [47]Ijima H. Nakamura S. Bual R.P. Yoshida K. Liver-specific extracellular matrix hydrogel promotes liver-specific functions of hepatocytes in vitro and survival of transplanted hepatocytes in vivo J Biosci Bioeng 2019 30935781

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Sorted by citations

Authors
Bual, R. P., & Ijima, H.
Affiliations
Kyushu University (JP)
Corresponding author
Ijima, Hiroyuki
ORCID
Venue
Regenerative Therapy
Publisher
Elsevier BV
Published
2019-12
Volume
11
Pages
258-268
ISSN
2352-3204 (ISSN-L)
DOI
10.1016/j.reth.2019.08.006
PMC
PMC6813644
OpenAlex
W2974283228
Cited by
30
References
3
Citations by year
2026: 1 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 4 · 2020: 3
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Regenerative Therapy (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Department of Science and Technology
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
liver extracellular matrix, pepsin solubilization, collagen preservation, hydrogel mechanical properties, liver-specific gene expression

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