Journal of Tissue Engineering and Regenerative Medicine

Volume 13, Issue 11 pp. 2067-2076

RESEARCH ARTICLE

Alteration of the extracellular matrix and alpha-gal antigens in the rat lung scaffold reseeded using human vascular and adipogenic stromal cells

Yasumasa Hashimoto

orcid.org/0000-0001-9363-6910

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Search for more papers by this author

Tomoshi Tsuchiya,

Tomoshi Tsuchiya

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan

Search for more papers by this author

Ryoichiro Doi,

Ryoichiro Doi

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Search for more papers by this author

Keitaro Matsumoto,

Keitaro Matsumoto

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Search for more papers by this author

Yoshikazu Higami,

Yoshikazu Higami

Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan

Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

Search for more papers by this author

Eiji Kobayashi,

Eiji Kobayashi

Center for Development of Advanced Medical Technology, Jichi Medical University, Tochigi, Japan

Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan

Search for more papers by this author

Takeshi Nagayasu,

Corresponding Author

Takeshi Nagayasu

[email protected]

orcid.org/0000-0002-0677-9364

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Correspondence

Takeshi Nagayasu, Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Email: [email protected]

Search for more papers by this author

Yasumasa Hashimoto,

Yasumasa Hashimoto

orcid.org/0000-0001-9363-6910

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Search for more papers by this author

Tomoshi Tsuchiya,

Tomoshi Tsuchiya

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan

Search for more papers by this author

Ryoichiro Doi,

Ryoichiro Doi

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Search for more papers by this author

Keitaro Matsumoto,

Keitaro Matsumoto

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Search for more papers by this author

Yoshikazu Higami,

Yoshikazu Higami

Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan

Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

Search for more papers by this author

Eiji Kobayashi,

Eiji Kobayashi

Center for Development of Advanced Medical Technology, Jichi Medical University, Tochigi, Japan

Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan

Search for more papers by this author

Takeshi Nagayasu,

Corresponding Author

Takeshi Nagayasu

[email protected]

orcid.org/0000-0002-0677-9364

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Correspondence

Takeshi Nagayasu, Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Email: [email protected]

Search for more papers by this author

First published: 02 July 2019

https://doi.org/10.1002/term.2923

Citations: 12

Share a link

Email
Wechat
Bluesky

Abstract

Regenerated organs are expected to solve the problem of donor organ shortage in transplantation medicine. One approach to lung regeneration is to decellularize the organ and reseed it with selected cells. An advantage of the procedure is reduced immunogenicity, because all cells can be theoretically replaced by autologous cells. However, little is known regarding the extracellular matrix (ECM) damage during decellularization and ECM reconstruction process in the organ regeneration. We aimed to evaluate ECM damage and reconstruction of the decellularized–recellularized rat lung, including the removal of alpha-gal xenoantigens. Rat lungs were perfused with sodium dodecyl sulfate and Triton X-100 via the pulmonary artery, after which the decellularized scaffold was reseeded with rat or human endothelial cells and adipose-derived stem cell (ASCs). The ECM and alpha-gal antigen were evaluated using immunohistochemistry, western blotting, and a glycosaminoglycan assay. Alcian blue staining revealed increased production of proteoglycan following the addition of ASCs to the rat lung recellularized with rat lung microvascular endothelial cells. Glycosaminoglycan levels decreased in the decellularized lung and increased in the recellularized lung, especially in the ASC-treated group. Immunohistochemical expression of the alpha-gal protein was decreased to an undetectable level in the decellularized lung tissue and disappeared after recellularization with human cells. In western blot analysis, the bands of alpha-gal protein almost disappeared after recellularization with human cells. In conclusion, characteristics of the regenerated ECM might depend on the species and type of cells used for recellularization. Therefore, alpha-gal antigen might be eliminated after a prolonged culture, when using human cells.

CONFLICT OF INTEREST

The authors have declared that there is no conflict of interest.

REFERENCES

Balestrini, J. L., Gard, A. L., Gerhold, K. A., Wilcox, E. C., Liu, A., Schwan, J., … White, E. S. (2016). Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine. Biomaterials, 102, 220–230. https://doi.org/10.1016/j.biomaterials.2016.06.025
10.1016/j.biomaterials.2016.06.025
CAS PubMed Web of Science® Google Scholar
Böer, U., Lohrenz, A., Klingenberg, M., Pich, A., Haverich, A., & Wilhelmi, M. (2011). The effect of detergent-based decellularization procedures on cellular proteins and immunogenicity in equine carotid artery grafts. Biomaterials, 32, 9730–9737. https://doi.org/10.1016/j.biomaterials.2011.09.015
10.1016/j.biomaterials.2011.09.015
CAS PubMed Web of Science® Google Scholar
Bussolino, F., Di Renzo, M. F., Ziche, M., Bocchietto, E., Olivero, M., Naldini, L., … Comoglio, P. M. (1992). Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. The Journal of Cell Biology, 119, 629–641. https://doi.org/10.1083/jcb.119.3.629
10.1083/jcb.119.3.629
CAS PubMed Web of Science® Google Scholar
Calle, E. A., Hill, R. C., Leiby, K. L., Le, A. V., Gard, A. L., Madri, J. A., … Niklason, L. E. (2016). Targeted proteomics effectively quantifies differences between native lung and detergent-decellularized lung extracellular matrices. Acta Biomaterialia, 46, 91–100. https://doi.org/10.1016/j.actbio.2016.09.043
10.1016/j.actbio.2016.09.043
CAS PubMed Web of Science® Google Scholar
Calle, E. A., Petersen, T. H., & Niklason, L. E. (2011). Procedure for lung engineering. Journal of Visualized Experiments, 49, 2651. https://doi.org/10.3791/2651
10.3791/2651
Web of Science® Google Scholar
Cissell, D. D., Hu, J. C., Griffiths, L. G., & Athanasiou, K. A. (2014). Antigen removal for the production of biomechanically functional, xenogeneic tissue grafts. Journal of Biomechanics, 47, 1987–1996. https://doi.org/10.1016/j.jbiomech.2013.10.041
10.1016/j.jbiomech.2013.10.041
PubMed Web of Science® Google Scholar
Doi, R., Tsuchiya, T., Mitsutake, N., Nishimura, S., Matsuu-Matsuyama, M., Nakazawa, Y., … Nagayasu, T. (2017). Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells. Scientific Reports, 7, 8447. https://doi.org/10.1038/s41598-017-09115-2
10.1038/s41598?017?09115?2
PubMed Web of Science® Google Scholar
Elder, B. D., Eleswarapu, S. V., & Athanasiou, K. A. (2009). Extraction techniques for the decellularization of tissue engineered articular cartilage constructs. Biomaterials, 30, 3749–3756. https://doi.org/10.1016/j.biomaterials.2009.03.050
10.1016/j.biomaterials.2009.03.050
CAS PubMed Web of Science® Google Scholar
Galili, U. (2001). The α-gal epitope (Galα1-3Galβ1-4GlcNAc-R) in xenotransplantation. Biochimie, 83, 557–563. https://doi.org/10.1016/S0300-9084(01)01294-9
10.1016/S0300?9084(01)01294?9
CAS PubMed Web of Science® Google Scholar
Nam, J., Choi, S. Y., Sung, S. C., Lim, H. G., Park, S. S., Kim, S. H., & Kim, Y. J. (2012). Changes of the structural and biomechanical properties of the bovine pericardium after the removal of α-gal epitopes by decellularization and α-galactosidase treatment. The Korean Journal of Thoracic and Cardiovascular Surgery, 45, 380–389. https://doi.org/10.5090/kjtcs.2012.45.6.380
10.5090/kjtcs.2012.45.6.380
PubMed Google Scholar
Naso, F., Gandaglia, A., Iop, L., Spina, M., & Gerosa, G. (2011). First quantitative assay of alpha-gal in soft tissues: Presence and distribution of the epitope before and after cell removal from xenogeneic heart valves. Acta Biomaterialia, 7, 1728–1734. https://doi.org/10.1016/j.actbio.2010.11.030
10.1016/j.actbio.2010.11.030
CAS PubMed Web of Science® Google Scholar
Petersen, T. H., Calle, E. A., Colehour, M. B., & Niklason, L. E. (2012). Matrix composition and mechanics of decellularized lung scaffolds. Cells, Tissues, Organs, 195, 222–231. https://doi.org/10.1159/000324896
10.1159/000324896
CAS PubMed Web of Science® Google Scholar
Prakash, Y. S., Tschumperlin, D. J., & Stenmark, K. R. (2015). Coming to terms with tissue engineering and regenerative medicine in the lung. American Journal of Physiology: Lung Cellular and Molecular Physiology, 309, L625–L638. https://doi.org/10.1152/ajplung.00204.2015
10.1152/ajplung.00204.2015
CAS PubMed Web of Science® Google Scholar
Sannes, P. L., Burch, K. K., Khosla, J., McCarthy, K. J., & Couchman, J. R. (1993). Immunohistochemical localization of chondroitin sulfate, chondroitin sulfate proteoglycan, heparan sulfate proteoglycan, entactin, and laminin in basement membranes of postnatal developing and adult rat lungs. American Journal of Respiratory Cell and Molecular Biology, 8, 245–251. https://doi.org/10.1165/ajrcmb/8.3.245
10.1165/ajrcmb/8.3.245
CAS PubMed Web of Science® Google Scholar
Stabler, C. T., Lecht, S., Mondrinos, M. J., Goulart, E., Lazarovici, P., & Lelkes, P. I. (2015). Revascularization of decellularized lung scaffolds: Principles and progress. American Journal of Physiology: Lung Cellular and Molecular Physiology, 309, L1273–L1285. https://doi.org/10.1152/ajplung.00237.2015
10.1152/ajplung.00237.2015
CAS PubMed Web of Science® Google Scholar
Tsuchiya, T., Balestrini, J. L., Mendez, J., Calle, E. A., Zhao, L., & Niklason, L. E. (2014). Influence of pH on extracellular matrix preservation during lung decellularization. Tissue Engineering Part C Methods, 20, 1028–1036. https://doi.org/10.1089/ten.TEC.2013.0492
10.1089/ten.TEC.2013.0492
CAS PubMed Web of Science® Google Scholar
Tsuchiya, T., Sivarapatna, A., Rocco, K., Nanashima, A., Nagayasu, T., & Niklason, L. E. (2014). Future prospects for tissue engineered lung transplantation. Organogenesis, 10, 197–207. https://doi.org/10.4161/org.27846
10.4161/org.27846
Web of Science® Google Scholar
van der Rest, M., & Garrone, R. (1991). Collagen family of proteins. The FASEB Journal, 5, 2814–2823. https://doi.org/10.1096/fasebj.5.13.1916105
10.1096/fasebj.5.13.1916105
PubMed Web of Science® Google Scholar
Wong, M. L., & Griffiths, L. G. (2014). Immunogenicity in xenogeneic scaffold generation: Antigen removal vs. decellularization. Acta Biomaterialia, 10, 1806–1816. https://doi.org/10.1016/j.actbio.2014.01.028
10.1016/j.actbio.2014.01.028
CAS PubMed Web of Science® Google Scholar
Woods, T., & Gratzer, P. F. (2005). Effectiveness of three extraction techniques in the development of a decellularized bone-anterior cruciate ligament-bone graft. Biomaterials, 26, 7339–7349. https://doi.org/10.1016/j.biomaterials.2005.05.066
10.1016/j.biomaterials.2005.05.066
CAS PubMed Web of Science® Google Scholar
Xu, H., Wan, H., Zuo, W., Sun, W., Owens, R. T., Harper, J. R., … McQuillan, D. J. (2009). A porcine-derived acellular dermal scaffold that supports soft tissue regeneration: removal of terminal galactose-alpha-(1,3)-galactose and retention of matrix structure. Tissue Engineering Part a, 15, 1807–1819. https://doi.org/10.1089/ten.tea.2008.0384
10.1089/ten.tea.2008.0384
CAS PubMed Web of Science® Google Scholar
Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., … Hedrick, M. H. (2001). Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Engineering, 7, 211–228. https://doi.org/10.1089/107632701300062859
10.1089/107632701300062859
CAS PubMed Google Scholar

Citing Literature

All articles

Alteration of the extracellular matrix and alpha-gal antigens in the rat lung scaffold reseeded using human vascular and adipogenic stromal cells

Abstract

CONFLICT OF INTEREST

REFERENCES

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Alteration of the extracellular matrix and alpha-gal antigens in the rat lung scaffold reseeded using human vascular and adipogenic stromal cells

Abstract

CONFLICT OF INTEREST

REFERENCES

Citing Literature

References

Related

Information