Journal of Artificial Organs

, Volume 21, Issue 2, pp 230–237 | Cite as

Vascularization of pancreatic decellularized scaffold with endothelial progenitor cells

Original Article Artificial Liver, Pancreas

Abstract

Vascularization remains a large obstacle for creating a functional pancreas-tissue equivalent for transplantation. In this study, a pre-vascularized pancreatic decellularized scaffold was prepared through endothelializing with endothelial progenitor cells (EPCs) in a bioreactor, and the ability to regenerate new blood vessels was detected in vivo. Initially, pancreases of Sprague–Dawley (SD) rats were perfused with 1% Triton X-100 and 0.1% ammonium hydroxide to remove the cellular components while the intact vascular network was preserved. Then, the decellularized scaffold was reseed with EPCs, which were primarily characterized by dual staining for dil-labeled acetylated low-density lipoprotein (Dil-acLDL) and fluorescein isothiocyanate labeled ulex europaeus agglutinin 1 (FITC-UEA-1), to reconstruct the vascular network. Thus, a scaffold covered with EPCs in the vessel structure was created. After that, the scaffold was transplanted into the rat in vivo to observe the anastomosis with the host vascular network. The results showed that EPCs can be located around the blood vessel wall, and re-endothelialized scaffold connected with the host through new blood vessel formation earlier than the control group (p < 0.05). These findings all indicated that the pancreatic decellularized scaffold endothelialized with EPCs may be further applied to solve the problem of blood supply and support the function of insulin-secreting cells after in vivo transplantation.

Keywords

Pancreas Decellularization Recellularization Endothelial progenitor cells Vascularization 

Notes

Acknowledgements

This research was supported by Grants from National Natural Science Foundation of China (No. 81471801, 81672903, 81502569), Medical Innovation Team Program of Jiangsu Province, Science and technology Project of Nantong City (MS12015017).

Compliance with ethical standards

Conflict of interest

Authors have no conflict of interest to declare.

Supplementary material

10047_2018_1017_MOESM1_ESM.doc (87.1 mb)
Supplementary material 1 (DOC 89139 KB)

References

  1. 1.
    Nawaz MS, Shah KU, Khan TM, Rehman AU, Rashid HU, Mahmood S, Khan S, Farrukh MJ. Evaluation of current trends and recent development in insulin therapy for management of diabetes mellitus. Diabetes Metab Syndr. 2017;S1871–4021:30157–1.Google Scholar
  2. 2.
    Ellis C, Ramzy A, Kieffer TJ. Regenerative medicine and cell-based approaches to restore pancreatic function. Nat Rev Gastroenterol Hepatol. 2017;14:612–28.PubMedGoogle Scholar
  3. 3.
    Goh SK, Bertera S, Olsen P, Candiello JE, Halfter W, Uechi G, Balasubramani M, Johnson SA, Sicari BM, Kollar E, Badylak SF, Banerjee I. Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering. Biomaterials. 2013;34:6760–72.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Traore MA, George SC. Tissue engineering the vascular tree. Tissue Eng Part B Rev. 2017;23:505–14.CrossRefPubMedGoogle Scholar
  5. 5.
    Wan J, Huang Y, Zhou P, Guo Y, Wu C, Zhu S, Wang Y, Wang L, Lu Y, Wang Z. Culture of iPSCs derived pancreatic β-Like cells in vitro using decellularized pancreatic scaffolds: a preliminary Trial. Biomed Res Int. 2017;2017:4276928.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Wu D, Wan J, Huang Y, Guo Y, Xu T, Zhu M, Fan X, Zhu S, Ling C, Li X, Lu J, Zhu H, Zhou P, Lu Y, Wang Z. 3D culture of MIN-6 cells on decellularized pancreatic scaffold: in vitro and in vivo study. BioMed Res Int. 2015;2015:432645.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Dew L, MacNeil S, Chong CK. Vascularization strategies for tissue engineers. Regen Med. 2015;10:211 – 24.CrossRefPubMedGoogle Scholar
  8. 8.
    Chong MS, Ng WK, Chan JK. Concise review: endothelial progenitor cells in regenerative medicine: applications and challenges. Stem Cells Transl Med. 2016;5:530–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zhou P, Huang Y, Guo Y, Wang L, Ling C, Guo Q, Wang Y, Zhu S, Fan X, Zhu M, Huang H, Lu Y, Wang Z. Decellularization and recellularization of rat livers with hepatocytes and endothelial progenitor cells. Artif Organs. 2016;40:E25–E38.CrossRefPubMedGoogle Scholar
  10. 10.
    Wang Y, Nicolas CT, Chen HS, Ross JJ, De Lorenzo SB, Nyberg SL. Recent advances in decellularization and recellularization for tissue-engineered liver grafts. Cells Tissues Organs. 2017;204:125–36.CrossRefPubMedGoogle Scholar
  11. 11.
    Yu Y, Alkhawaji A, Ding Y, Mei J. Decellularized scaffolds in regenerative medicine. Oncotarget. 2016;7:58671–83.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Keane TJ, Londono R, Turner NJ, Badylak SF. Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials. 2012;33:1771–81.CrossRefPubMedGoogle Scholar
  13. 13.
    Vigier S, Gagnon H, Bourgade K, Klarskov K, Fülöp T, Vermette P. Composition and organization of the pancreatic extracellular matrix by combined methods of immunohistochemistry, proteomics and scanning electron microscopy. Curr Res Transl Med. 2017;65:31–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Keane TJ, Badylak SF. The host response to allogeneic and xenogeneic biological scaffold materials. J Tissue Eng Regen Med. 2015;9:504 – 11.CrossRefPubMedGoogle Scholar
  15. 15.
    Stabler CT, Lecht S, Mondrinos MJ, Goulart E, Lazarovici P, Lelkes PI. Revascularization of decellularized lung scaffolds: principles and progress. Am J Physiol Lung Cell Mol Physiol. 2015;309:L1273–L85.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Brandl A, Yuan Q, Boos AM, Beier JP, Arkudas A, Kneser U, Horch RE, Bleiziffer O. A novel early precursor cell population from rat bone marrow promotes angiogenesis in vitro. BMC Cell Biol. 2014;15:12.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Siavashi V, Nassiri SM, Rahbarghazi R, Vafaei R, Sariri R. ECM-dependence of endothelial progenitor cell features. J Cell Biochem. 2016;117:1934–46.CrossRefPubMedGoogle Scholar
  18. 18.
    Liu X, Chen W, Zhang C, Thein-Han W, Hu K, Reynolds MA, Bao C, Wang P, Zhao L, Xu HHK. Co-seeding human endothelial cells with human-induced pluripotent stem cell-derived mesenchymal stem cells on calcium phosphate scaffold enhances osteogenesis and vascularization in rats. Tissue Eng Part A. 2017;23:546–55.CrossRefPubMedGoogle Scholar
  19. 19.
    Mishra R, Roux BM, Posukonis M, Bodamer E, Brey EM, Fisher JP, Dean D. Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds. Biomaterials. 2016;77:255 – 66.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2018

Authors and Affiliations

  • Yibing Guo
    • 1
  • Cen Wu
    • 3
  • Liancheng Xu
    • 1
    • 2
  • Yang Xu
    • 1
    • 2
  • Li Xiaohong
    • 1
  • Zhu Hui
    • 1
  • Lu Jingjing
    • 1
  • Yuhua Lu
    • 1
    • 2
  • Zhiwei Wang
    • 2
  1. 1.Research center of clinical medicalAffiliated Hospital of Nantong UniversityJiangsuChina
  2. 2.Department of General SurgeryAffiliated Hospital of Nantong UniversityJiangsuChina
  3. 3.Department of General SurgeryRudong County People’s HospitalJiangsuChina

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