Comparative immunogenicity of decellularized wild type and alpha 1,3 galactosyltransferase knockout pig lungs
Abstract
Decellularized pig lungs recellularized with human lung cells offer a novel approach for organ transplantation. However, the potential immunogenicity of decellularized pig lungs following exposure to human tissues has not been assessed. We found that exposure of native lungs from wildtype and transgenic pigs lacking alpha (1,3)-galactosyltransferase (α-gal KO) to sera from normal healthy human volunteers demonstrated similar robust IgM and IgG immunoreactivity, comparably decreased in decellularized lungs. Similar results were observed with sera from patients who had previously undergone transcutaneous porcine aortic valve replacement (TAVR) or from patients with increased circulating anti-α-gal IgE antibodies (α-gal syndrome). Depleting anti-α-gal antibodies from the sera demonstrated both specificity of α-gal immunoreactivity and also residual immunoreactivity similar between wildtype and α-gal KO pig lungs. Exposure of human monocytes and macrophages to native wildtype lungs demonstrated greater induction of M2 phenotype than native α-gal KO pig lungs, which was less marked with decellularized lungs of either type. Overall, these results demonstrate that native wildtype and α-gal KO pig lungs provoke similar immune responses that are comparably decreased following decellularization. This provides a further platform for potential use of decellularized pig lungs in tissue engineering approaches and subsequent transplantation schemes but no obvious overall immunologic advantage of utilizing lungs obtained from α-gal KO pigs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ECM alterations impede subsequent recellularization and consequently increase availability of present antigenic sites for the host immune system.
“The second mechanism is related to the ECM alterations, which impede subsequent recellularization [51] and consequently increase the availability of present antigenic sites for the host immune system [64].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [64]
Cites
Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose
Chung, C. H., Mirakhur, B., Chan, E., Le, Q.-T., Berlin, J., Morse, M., Murphy, B. A., Satinover, S. M., Hosen, J., Mauro, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa074943 · Cited by 1,521 · see citing works
Morrison, T. J., Jackson, M. V., Cunningham, E. K., Kissenpfennig, A., McAuley, D. F., O’Kane, C. M., & Krasnodembskaya, A. D. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201701-0170oc · Cited by 796 · see citing works
A unique natural human IgG antibody with anti-alpha-galactosyl specificity.
Galili, U., Rachmilewitz, E. A., Peleg, A., & Flechner, I. (1984) · The Journal of Experimental Medicine · doi:10.1084/jem.160.5.1519 · Cited by 705 · see citing works
Early failure of the tissue engineered porcine heart valve SYNERGRAFT™ in pediatric patients
Simon, P. (2003) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/s1010-7940(03)00094-0 · Cited by 623 · see citing works
Price, A., England, K. A., Matson, A. M., Blazar, B. R., & Panoskaltsis‐Mortari, A. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0659 · Cited by 344 · see citing works
Dalmasso, A. P., Vercellotti, G. M., Fischel, R. J., Bolman, R. M., III, Bach, F. H., & Platt, J. L. (1992) · PubMed Central · Cited by 250 · see citing works
Alpha‐Gal on bioprostheses: xenograft immune response in cardiac surgery
Konakci, K. Z., Bohle, B., Blumer, R., Hoetzenecker, W., Roth, G. A., Moser, B., Boltz‐Nitulescu, G., Gorlitzer, M., Klepetko, W., Wolner, E., et al. (2005) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2005.01441.x · Cited by 247 · see citing works
Daly, A. B., Wallis, J. M., Borg, Z. D., Bonvillain, R. W., Deng, B., Ballif, B. A., Jaworski, D. M., Allen, G. B., & Weiss, D. J. (2011) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0301 · Cited by 203 · see citing works
Self-citationRethinking Regenerative Medicine: A Macrophage-Centered Approach
Brown, B. N., Sicari, B. M., & Badylak, S. F. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00510 · Cited by 187 · see citing works
Comparative decellularization and recellularization of normal versus emphysematous human lungs
Wagner, D. E., Bonenfant, N. R., Parsons, C. S., Sokocevic, D., Brooks, E. M., Borg, Z. D., Lathrop, M. J., Wallis, J. D., Daly, A. B., Lam, Y. W., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.12.103 · Cited by 172 · see citing works
Self-citationMacrophage phenotype in response to ECM bioscaffolds
Huleihel, L., Dziki, J. L., Bartolacci, J. G., Rausch, T., Scarritt, M. E., Cramer, M. C., Vorobyov, T., LoPresti, S. T., Swineheart, I. T., White, L. J., et al. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.04.004 · Cited by 169 · see citing works
Bonvillain, R. W., Danchuk, S. D., Sullivan, D. E., Betancourt, A. M., Semon, J. A., Eagle, M. E., Mayeux, J. P., Gregory, A. N., Wang, G., Townley, I. K., et al. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0594 · Cited by 163 · see citing works
Self-citationDecellularized matrices for cardiovascular tissue engineering.
Moroni, F., & Mirabella, T. (2014) · Europe PMC (PubMed Central) · Cited by 149 · see citing works
Extracellular Matrix Bioscaffolds as Immunomodulatory Biomaterials <sup/>
Dziki, J. L., Huleihel, L., Scarritt, M. E., & Badylak, S. F. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0538 · Cited by 141 · see citing works
Wagner, D. E., Bonenfant, N. R., Sokocevic, D., DeSarno, M., Borg, Z. D., Parsons, C. S., Brooks, E. M., Platz, J. J., Khalpey, Z. I., Hoganson, D. M., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.078 · Cited by 140 · see citing works
Self-citationKeane, T. J., & Badylak, S. F. (2015) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.1874 · Cited by 139 · see citing works
Commins, S. P., & Platts‐Mills, T. A. E. (2012) · Current Allergy and Asthma Reports · doi:10.1007/s11882-012-0315-y · Cited by 134 · see citing works
Self-citationMohiuddin, M. M., Singh, A. K., Corcoran, P. C., Hoyt, R. F., Thomas, M. L., Ayares, D., & Horvath, K. A. (2014) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2014.06.002 · Cited by 132 · see citing works
Xu, H. M., Wan, H., Zuo, W., Sun, W. Q., Owens, R. T., Harper, J. R., Ayares, D., & McQuillan, D. J. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0384 · Cited by 121 · see citing works
Wagner, D. E., Bonvillain, R. W., Jensen, T., Girard, E. D., Bunnell, B. A., Finck, C. M., Hoffman, A. M., & Weiss, D. J. (2013) · Respirology · doi:10.1111/resp.12102 · Cited by 115 · see citing works
Self-citationHawkins, R. B., Frischtak, H., Kron, I. L., & Ghanta, R. K. (2016) · Journal of Cardiac Surgery · doi:10.1111/jocs.12764 · Cited by 97 · see citing works
Presence and Elimination of the Xenoantigen Gal (α1, 3) Gal in Tissue-Engineered Heart Valves
Kasimir, M., Rieder, E., Seebacher, G., Wolner, E., Weigel, G., & Simon, P. (2005) · Tissue Engineering · doi:10.1089/ten.2005.11.1274 · Cited by 97 · see citing works
Bioprosthetic heart valves of the future
Manji, R. A., Ekser, B., Menkis, A. H., & Cooper, D. K. C. (2014) · Xenotransplantation · doi:10.1111/xen.12080 · Cited by 93 · see citing works
Mozzicato, S., Tripathi, A., Posthumus, J., Platts‐Mills, T. A. E., & Commins, S. P. (2014) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2014.04.016 · Cited by 86 · see citing works
Self-citationAnaphylaxis after zoster vaccine: Implicating alpha-gal allergy as a possible mechanism
Stone, C. A., Hemler, J. A., Commins, S. P., Schuyler, A. J., Phillips, E. J., Peebles, R. S., & Fahrenholz, J. M. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.10.037 · Cited by 85 · see citing works
Self-citationStahl, E. C., Bonvillain, R. W., Skillen, C. D., Burger, B. L., Hara, H., Lee, W., Trygg, C. B., Didier, P. J., Grasperge, B. F., Pashos, N. C., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.09.038 · Cited by 72 · see citing works
Self-citationAlpha‐gal is a possible target of IgE‐mediated reactivity to antivenom
Fischer, J., Eberlein, B., Hilger, C., Eyer, F., Eyerich, S., Ollert, M. W., & Biedermann, T. (2016) · Allergy · doi:10.1111/all.13073 · Cited by 65 · see citing works
Alpha-Gal Specific IgG Immune Response after Implantation of Bioprostheses
Mangold, A., Szerafin, T., Höetzenecker, K., Hacker, S., Lichtenauer, M., Niederpold, T., Nickl, S., Dworschak, M., Blumer, R., Auer, J., et al. (2009) · The Thoracic and Cardiovascular Surgeon · doi:10.1055/s-0029-1185395 · Cited by 64 · see citing works
How to build a lung: latest advances and emerging themes in lung bioengineering
Santis, M. M. D., Bölükbas, D. A., Lindstedt, S., & Wagner, D. E. (2018) · European Respiratory Journal · doi:10.1183/13993003.01355-2016 · Cited by 61 · see citing works
Anti‐Galα1‐3Gal IgM and IgG antibody levels in sera of humans and old world non‐human primates
Teranishi, K., Máñez, R., Awwad, M., & Cooper, D. K. C. (2002) · Xenotransplantation · doi:10.1034/j.1399-3089.2002.1o058.x · Cited by 59 · see citing works
Anti alpha-gal immune response following porcine bioprosthesis implantation in children.
Park, C. S., Park, S., Choi, S. Y., Yoon, S. H., Kim, W., & Kim, Y. J. (2010) · PubMed · Cited by 57 · see citing works
Discovery of the natural anti‐Gal antibody and its past and future relevance to medicine
Galili, U. (2013) · Xenotransplantation · doi:10.1111/xen.12034 · Cited by 56 · see citing works
Choi, S.-Y., Jeong, H., Lim, H., Park, S., Kim, S.-H., & Kim, Y. J. (2012) · PubMed · Cited by 50 · see citing works
Dunkman, W. J., Rycek, W., & Manning, M. W. (2018) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000003460 · Cited by 47 · see citing works
Platz, J. J., Bonenfant, N. R., Uhl, F. E., Coffey, A. L., McKnight, T., Parsons, C. S., Sokocevic, D., Borg, Z. D., Lam, Y., Deng, B., et al. (2016) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2016.0109 · Cited by 45 · see citing works
Self-citationMcGregor, C. G. A., Kogelberg, H., Vlašín, M., & Byrne, G. W. (2013) · PubMed · Cited by 39 · see citing works
Bioengineering Lungs for Transplantation
Gilpin, S. E., Charest, J. M., Ren, X., & Ott, H. C. (2016) · Thoracic surgery clinics/Thorac. surg. clin. · doi:10.1016/j.thorsurg.2015.12.004 · Cited by 37 · see citing works
Lectin binding patterns to terminal sugars of rat lung alveolar epithelial cells.
Taatjes, D. J., Barcomb, L. A., Leslie, K. O., & Low, R. B. (1990) · Journal of Histochemistry & Cytochemistry · doi:10.1177/38.2.1688898 · Cited by 35 · see citing works
Self-citationAnaphylaxis to medications containing meat byproducts in an alpha-gal sensitized individual
Muglia, C., Kar, I., Gong, M., DeSantis, E. R. H., & Monteleone, C. A. (2015) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2015.04.004 · Cited by 23 · see citing works
Poulis, N., Zaytseva, P., Gähwiler, E. K. N., Motta, S. E., Fioretta, E. S., Cesarovic, N., Falk, V., Hoerstrup, S. P., & Emmert, M. Y. (2020) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2020.1792777 · Cited by 22 · see citing works
When meat allergy meets cardiac surgery: A driver for humanized bioprosthesis
Ankersmit, H. J., Copic, D., & Simader, E. (2017) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2017.05.041 · Cited by 5 · see citing works
Studying Xenograft Rejection of Bioprosthetic Heart Valves
Manji, R. A., & Manji, J. S. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0255-3_15 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316 · see citing works
Zhu, D., Jiang, Z., Li, N., Wang, X., Ren, L., Ye, Y., Pan, Y., & Yang, G. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114413 · Cited by 31 · see citing works
Decellularization of fish tissues for tissue engineering and regenerative medicine applications
Chen, W., Chen, M., Chen, S., Wang, S., Huang, Z., Zhang, L., Wu, J., Peng, W., Li, H., & Wen, F. (2024) · Regenerative Biomaterials · doi:10.1093/rb/rbae138 · Cited by 25 · see citing works
Wang, Y., Wen, F., Yao, X., Zeng, L., Wu, J., He, Q., Li, H., & Fang, L. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.811652 · Cited by 25 · see citing works
Ex vivo organ engineering using decellularized tissue scaffolds
Saleh, T., Caciolli, L., Giobbe, G. G., & Coppi, P. D. (2025) · Nature Reviews Bioengineering · doi:10.1038/s44222-025-00322-5 · Cited by 11 · see citing works
Zhu, X., Yang, Y., Mao, S., Liu, Q., Li, Y., Yang, Y., Gao, M., Bao, J., Li, W., & Li, Y. (2024) · Biofabrication · doi:10.1088/1758-5090/ada092 · Cited by 11 · see citing works
Naso, F., Gandaglia, A., Sturaro, G., Galli, C., & Melder, R. J. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2905181 · Cited by 7 · see citing works
The journey of decellularized vessel: from laboratory to operating room
Kang, C., & Yang, H. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1413518 · Cited by 6 · see citing works
Weiss, D. J. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1130074 · Cited by 6 · see citing works
Self-citationHo, W.-J., Kobayashi, M., Murata, K., Hashimoto, Y., Izumi, K., Kimura, T., Kanemitsu, H., Yamazaki, K., Ikeda, T., Minatoya, K., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-26792-w · Cited by 5 · see citing works
Stelcer, E., Woźniak, A., Magner, D., & Zeyland, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1663246 · Cited by 4 · see citing works
Evaluation of a decellularized bronchial patch transplant in a porcine model
Taniguchi, D., Kamata, S., Rostami, S., Tuin, S. A., Marin‐Araujo, A. E., Guthrie, K., Petersen, T. H., Waddell, T. K., Karoubi, G., Keshavjee, S. H., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-48643-y · Cited by 2 · see citing works
Self-citationHo, W.-J., Kobayashi, M., Murata, K., Hashimoto, Y., Izumi, K., Kimura, T., Kanemitsu, H., Yamazaki, K., Ikeda, T., Minatoya, K., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-2104137/v1 · Cited by 1 · see citing works
Taatjes, D. J., & Roth, J. (2021) · Histochemistry and Cell Biology · doi:10.1007/s00418-021-02035-3
Self-citationJiang, H. X., Wang, S., Zhou, Z., Chen, J., Huang, C., Liu, W. T., Jia, Z., Wu, J., Ye, J., Xiong, Y., et al. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08263-2
Zhu, Y., Wang, Z., Song, B., & Qian, Z. (2026) · Chinese Chemical Letters · doi:10.1016/j.cclet.2026.113426
- Authors
- Gasek, N., Dearborn, J., Enes, S. R., Pouliot, R., Louie, J., Phillips, Z., Wrenn, S., Uhl, F. E., Riveron, A., Bianchi, J., Commins, S. P., Delance, N., Taatjes, D. J., Boyson, J. E., Guthrie, K., Petersen, T. H., & Weiss, D. J.
- Affiliations
- University of Vermont (US)
- Danbury Hospital (US)
- University of North Carolina at Chapel Hill (US)
- United Therapeutics (United States) (US)
- Corresponding author
- Weiss, Daniel J.
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 276
- Pages
- 121029
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W3181705072
- Cited by
- 16
- References
- 43
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 2
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1s10od025030-01)
- National Heart, Lung, and Blood Institute (R01HL127144)
- National Center for Research Resources (S10RR019246)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Health Sciences › Medicine › Transplantation › Organ and Tissue Transplantation Research
- Keywords
- immunogenicity, xenotransplantation, alpha-gal syndrome, M2 macrophage polarization, monocytes, lung tissue engineering
- MeSH terms
- Animals, Bioprosthesis, Food Hypersensitivity, Galactosyltransferases, Heart Valve Prosthesis, Humans, Lung, Swine, Transplantation, Heterologous
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
