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Fluidized-bed bioartificial liver assist devices (BLADs) based on microencapsulated primary porcine hepatocytes have risk of porcine endogenous retroviruses transmission
Open accessAbstract
Purpose Bioartificial liver assist devices (BLADs) are expected to bridge liver failure patients to liver transplantation, but porcine endogenous retroviruses (PERVs) still pose a potential risk in pig-to-human xenotransplantation and thereby limit the use of bioartificial liver therapy. In our lab, fluidized-bed BLADs based on microencapsulated primary porcine hepatocytes have been successfully used to treat liver failure pigs. We detected the risk of PERVs transmission of microencapsulated primary porcine hepatocytes-the key component of fluidized-bed BLADs, to evaluate the biosafety of this device for further clinical applications. Methods Microencapsulated primary porcine hepatocytes (cell diameter = 300 μm) were cultured in Dulbecco's modified Eagles medium (DMEM). Microencapsulated cell culture supernatants were collected at 6, 12, 24 and 72 h. HEK-293 were cocultured with these supernatants, and the cocultured cells were harvested every 7 days. RT-PCR was used to detect PERVs transmission. RT-qPCR was used to get the number of virus copies. PK-15 was used as the positive control whereas HepG2 was used as the negative control. Results PERV was detected in all supernatants, and the viral load of the supernatants increased with time. Moreover, cocultured 293 cells were positive for PERV-specific sequences. Conclusion The kind of fluidized-bed BLADs based on microencapsulated primary porcine hepatocytes have risk of PERVs transmission. Further extensive pre-clinical study focused on biosafety is warranted.
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Porcine primary hepatocytes have drawbacks that could hinder their potential application in clinic, such as potential immunogenic reaction induced by proteins produced by porcine cells and risk of transferring viral pathogens, such as PERV, porcine cytomegalovirus, and porcine lymphotropic herpesvirus.
“Porcine primary hepatocytes have drawbacks that could hinder their potential application in clinic, such as the potential immunogenic reaction induced by proteins produced by porcine cells and the risk of transferring viral pathogens, such as PERV, porcine cytomegalovirus, and porcine lymphotropic herpesvirus [[199], [200], [201], [202]].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [201]
Citations
Cites
Infection of human cells by an endogenous retrovirus of pigs
Patience, C., Takeuchi, Y., & Weiss, R. A. (1997) · Nature Medicine · doi:10.1038/nm0397-282 · Cited by 953
Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure
Ellis, A. J., Hughes, R. D., Wendon, J. A., Dunne, J., Langley, P. G., Kelly, J. H., Gislason, G., Sussman, N., & Williams, R. L. (1996) · Hepatology · doi:10.1002/hep.510240625 · Cited by 525
Clinical Experience With a Bioartificial Liver in the Treatment of Severe Liver Failure
Watanabe, F. D., Mullon, C. J. P., Hewitt, W. R., Arkadopoulos, N., Kahaku, E., Eguchi, S., Khalili, T. M., Arnaout, W. S., Shackleton, C. R., Rózga, J., et al. (1997) · Annals of Surgery · doi:10.1097/00000658-199705000-00005 · Cited by 450
Lanza, R., Hayes, J. L., & Chick, W. L. (1996) · Nature Biotechnology · doi:10.1038/nbt0996-1107 · Cited by 206
Clinical Application of Bioartificial Liver Support Systems
van de Kerkhove, M. P., Hoekstra, R., Chamuleau, R. A. F. M., & van Gulik, T. M. (2004) · Annals of Surgery · doi:10.1097/01.sla.0000132986.75257.19 · Cited by 206
Hering, B. J., Cozzi, E., Spizzo, T., Cowan, P. J., Rayat, G. R., Cooper, D. K. C., & Denner, J. (2016) · Xenotransplantation · doi:10.1111/xen.12231 · Cited by 118
Evidence and Consequence of Porcine Endogenous Retrovirus Recombination
Bartosch, B., Stefanidis, D., Myers, R. E., Weiss, R. A., Patience, C., & Takeuchi, Y. (2004) · Journal of Virology · doi:10.1128/jvi.78.24.13880-13890.2004 · Cited by 118
Mazariegos, G. V., Kramer, D. J., López, R., Shakil, A. O., Rosenbloom, A. J., Devera, M., Giraldo, M., Grogan, T. A., Zhu, Y., Fulmer, M. L., et al. (2001) · ASAIO Journal · doi:10.1097/00002480-200109000-00015 · Cited by 116
Primary Human Liver Cells as Source for Modular Extracorporeal Liver Support - a Preliminary Report
Sauer, I. M., Zeilinger, K., Obermayer, N., Pless, G., Grünwald, A., Pascher, A., Mieder, T., Roth, S., Goetz, M., Kardassis, D., et al. (2002) · The International Journal of Artificial Organs · doi:10.1177/039139880202501015 · Cited by 115
Recombinant porcine endogenous retroviruses (PERV-A/C): a new risk for xenotransplantation?
Denner, J. (2008) · Archives of Virology · doi:10.1007/s00705-008-0141-7 · Cited by 110
Chapter 5: Strategies to prevent transmission of porcine endogenous retroviruses
Denner, J., Schuurman, H., & Patience, C. (2009) · Xenotransplantation · doi:10.1111/j.1399-3089.2009.00544.x · Cited by 92
Artificial and Bioartificial Liver Support
McKenzie, T. J., Lillegard, J. B., & Nyberg, S. L. (2008) · Seminars in Liver Disease · doi:10.1055/s-2008-1073120 · Cited by 91
Switzer, W. M., Shanmugam, V., Chapman, L. E., & Heneine, W. (1999) · Transplantation · doi:10.1097/00007890-199907270-00003 · Cited by 67
Ritzhaupt, A., van der Laan, L. J. W., Salomon, D. R., & Wilson, C. A. (2002) · Journal of Virology · doi:10.1128/jvi.76.22.11312-11320.2002 · Cited by 67
Naruse, K. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i10.1516 · Cited by 65
A New Concept of Bioartificial Liver Based on a Fluidized Bed Bioreactor
Doré, E., & Legallais, C. (1999) · Therapeutic Apheresis and Dialysis · doi:10.1046/j.1526-0968.1999.00152.x · Cited by 49
Hwang, S., Lee, S., Ahn, C., Kim, K., Moon, D., Ha, T., Song, G., Jung, D., Park, J.-I., Ryu, J.-H., et al. (2008) · Liver Transplantation · doi:10.1002/lt.21440 · Cited by 46
Lim, G. J., Zare, S., Dyke, M. E. V., & Atala, A. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-5786-3_11 · Cited by 39
Mass Transfers in a Fluidized Bed Bioreactor using Alginate Beads for a Future Bioartificial Liver
David, B., Doré, E., Jaffrin, M. Y., & Legallais, C. (2004) · The International Journal of Artificial Organs · doi:10.1177/039139880402700404 · Cited by 37
Porcine endogenous retrovirus released by a bioartificial liver infects primary human cells
Frühauf, J., Mertsching, H., Giri, S., Frühauf, N. R., & Bader, A. (2009) · Liver International · doi:10.1111/j.1478-3231.2009.02087.x · Cited by 35
Culture of C3A Cells in Alginate Beads for Fluidized Bed Bioartificial Liver
Kinasiewicz, A., Gautier, A., Lewińska, D., Bukowski, J., Legallais, C., & Weryński, A. (2007) · Transplantation Proceedings · doi:10.1016/j.transproceed.2007.08.062 · Cited by 30
Kinasiewicz, A., Gautier, A., Lewińska, D., Smietanka, A., Legallais, C., & Weryński, A. (2008) · The International Journal of Artificial Organs · doi:10.1177/039139880803100411 · Cited by 28
Recombinant porcine endogenous retroviruses (PERV‐A/C): a new risk for xenotransplantation?
Denner, J. (2010) · Xenotransplantation · doi:10.1111/j.1399-3089.2010.00573_21.x · Cited by 26
Islet cell transplantation for the treatment of diabetes mellitus
Kendall, W. F., Collins, B. H., & Opara, E. C. (2001) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.1.1.109 · Cited by 25
Yu, C., Lv, G., Pan, X., Chen, Y., Cao, H., Zhang, Y., Du, W., Yang, S., & Li, L. (2009) · The International Journal of Artificial Organs · doi:10.1177/039139880903200504 · Cited by 17
Self-citationMicroencapsulated hepatocytes and islets asin vivobioartificial liver support system
Gao, Y. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i14.2067 · Cited by 15
Development of bioartificial liver system using a fluidized-bed bioreactor
Hwang, Y. J., Kim, Y. I., Lee, J. G., Lee, J. W., Kim, J. W., & Chung, J. M. (2000) · Transplantation Proceedings · doi:10.1016/s0041-1345(00)01695-x · Cited by 12
Bioartificial Liver System using a Fluidized-Bed Bioreactor
Hwang, Y. J., Kim, J. Y., Chang, S. K., Kim, S. G., Kim, Y. I., & Hwang, J.-H. (2008) · Annals of Hepato-Biliary-Pancreatic Surgery · Cited by 2
Endogenne wirusy swini [PERV] jako zagrozenia w ksenotransplantacjach
Machnik, G., Sypniewski, D., Mazurek, U. M., Rożek-Kostórkiewicz, J., & Wilczok, T. (2004) · Medycyna Weterynaryjna · Cited by 2
Activity of cells within alginate beads produced for fluidized bed bioreactor (bioartificial liver).
Kinasiewicz, A., Gautier, A., Lewińska, D., Dufresne, M., Paullier, P., Bukowski, J., Legallais, C., & Weryńsky, A. (2006) · HAL · Cited by 1
生体外での機械的刺激下の「バイオ管」の改良型構造および機械的特性
Kanda, K., Huang, H., Sakai, O., Hayashida, K., Watanabe, T., Yaku, H., Ando, J., & Nakayama, Y. (2006) · The International Journal of Artificial Organs · Cited by 1
Flagged first, then by citations
Research works printed but not linked: 4
- Diekmann S, Glockner P, Mittag A, Tarnok A, Bader A. Encapsulated hepatocytes for the application in a bioartificial liver support system. Cytometry A 2007;71A:516–517
- Carpentier B, Gautier A, Paullier R, Legallais C. Mass transfer studies in a model of fluidized bed bioartificial liver. Int J Artif Organs 2006;29:509–512
- Machnik G, Sypniewski D, Mazurek U, Rozek-Kostorkiewicz J, Wilczok T. Hazards of porcine endogenous retroviruses (PERVs) in xenotransplantation. Med Weter 2004;60:345–348
- Aoki K, Hakamada K, Seino K, Umehara Y, Itabashi Y, Sasaki M. Development of a bioartificial liver using microencapsulated xenohepatocytes. New Directions for Cellular and Organ Transplantation, vol 1210. 2000. p. 55–59
Cited by
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Liver tissue engineering and cell sources: issues and challenges
Palakkan, A. A., Hay, D. C., PR, A. K., TV, K., & Ross, J. A. (2013) · Liver International · doi:10.1111/liv.12134 · Cited by 130
“The main concerns in using xenogenic porcine hepatocytes is the transfer of zoonotic diseases (87), protein–protein incompatibility and the possible immune responses generated during treatment (88–90).”
BackgroundLee, S. Y., Kim, H., & Choi, D. (2015) · International Journal of Stem Cells · doi:10.15283/ijsc.2015.8.1.36 · Cited by 81
“However, transfer of zoonotic diseases (15), protein-protein incompatibility between species and possible immune responses generated during treatment remain challenges for the use of xenogeneic hepatocytes (16).”
BackgroundAdvances in cell sources of hepatocytes for bioartificial liver
Pan, X., & Li, L. (2012) · Hepatobiliary & pancreatic diseases international · doi:10.1016/s1499-3872(12)60230-6 · Cited by 32
Self-citationTran, N. M., Dufresne, M., Duverlie, G., Castelain, S., Défarge, C., Paullier, P., & Legallais, C. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2012.0139 · Cited by 31
Development of a 3D porous chitosan/gelatin liver scaffold for a bioartificial liver device
Hou, Y., & Hsu, C.-C. (2020) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2019.12.012 · Cited by 31
Hussein, K. H., Ahmadzada, B., Correa, J. C., Sultan, A., Wilken, S., Amiot, B., & Nyberg, S. L. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.06.001 · Cited by 28
Bioartificial livers: a review of their design and manufacture
Tuerxun, K., He, J., Ibrahim, I., Yusupu, Z., Yasheng, A., Xu, Q., Tang, R., Aikebaier, A., Wu, Y., Tuerdi, M., et al. (2022) · Biofabrication · doi:10.1088/1758-5090/ac6e86 · Cited by 24
“However, the use of fluidized bed BAL devices includes the risk of porcine endogenous retrovirus (PERV) transmission [20].”
HepaRG Self-Assembled Spheroids in Alginate Beads Meet the Clinical Needs for Bioartificial Liver
Pasqua, M., Pereira, U., Messina, A., de Lartigue, C., Vigneron, P., Dubart‐Kupperschmitt, A., & Legallais, C. (2020) · Tissue Engineering Part A · doi:10.1089/ten.tea.2019.0262 · Cited by 22
Detection of porcine endogenous retrovirus in xenotransplantation
Gola, J. M., & Mazurek, U. M. (2014) · Reproductive Biology · doi:10.1016/j.repbio.2014.01.006 · Cited by 17
Encapsulation and Fluidization Maintains the Viability and Glucose Sensitivity of Beta-Cells
Nikravesh, N., Cox, S. C., Ellis, M. J., & Grover, L. M. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00191 · Cited by 12
Evaluation of a reversibly immortalized human hepatocyte line in bioartificial liver in pigs
Zhao, L. (2012) · AFRICAN JOURNAL OF BIOTECHNOLOGY · doi:10.5897/ajb11.3411 · Cited by 9
“through the immune barrier in AC microbeads (Yang et al., 2010).”
BackgroundYudin, N. S., Айтназаров, Р. Б., & Ермолаев, В. И. (2011) · Russian Journal of Genetics Applied Research · doi:10.1134/s207905971106013x · Cited by 4
“RNA expression of PERV has been found in several types of tissue, including kidney, lung, skin, liver, and pancreatic islands (Le Tissier et al., 1997; Patience et al., 1997; Akiyoshi et al., 1998; Martin et al., 1998a; van der Laan et al., 2000; Yang et al., 2010).”
BackgroundMembrane Approaches for Liver and Neuronal Tissue Engineering
Morelli, S., Salerno, S., Piscioneri, A., Rende, M., Campana, C., & Bartolo, L. D. (2010) · Elsevier eBooks · doi:10.1016/b978-0-08-093250-7.00016-5 · Cited by 4
Xenotransplantation literature update, January–February 2011
Schneider, M. K. J., & Seebach, J. D. (2011) · Xenotransplantation · doi:10.1111/j.1399-3089.2011.00630.x · Cited by 2
“[15] investigated the risk of porcine endogenous retrovirus (PERV) transmission from MPPH.”
BackgroundWittebole, X., Castanares‐Zapatero, D., Collienne, C., Ciccarelli, O., Hantson, P. E., & Laterre, P. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-398523-1.00023-9 · Cited by 2
Kim, Y.-H., Özer, S., & Uygun, B. E. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-398523-1.00024-0 · Cited by 1
Liver Regeneration and Tissue Engineering
Zhou, Q., Fan, L., & Li, . (2020) · Springer eBooks · doi:10.1007/978-981-15-5984-6_4 · Cited by 1
Cells for Bioartifi cial Liver Support
Hodgson, H. J. F., Thomas, A., & Selden, C. (2012) · Science Publishers eBooks · doi:10.1201/b11937-9
Current Status and New Challenges of the Artificial Liver
Mizumoto, H., Shirakigawa, N., & Ijima, H. (2018) · Wiley eBooks · doi:10.1002/9781119296034.ch3
4.12 Membrane Approaches for Liver and Neuronal Tissue Engineering
Morelli, S., Salerno, S., Piscioneri, A., & Bartolo, L. D. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12260-7
Whole-liver bioengineering: The future of transplantation medicine
Marques, D., Romero, N. S., Barbancho, S. M., Blanes-Rodríguez, Á., Arnal, P., Almeida, H., Dachary, P. R., & Baptista, P. M. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-823524-9.00018-6
Preclinical studies on an extracorporeal bioartificial liver
Pasqua, M. (2020) · theses.fr (ABES) · doi:10.70675/80737894z778az43e7zba8bzdc445e5d436f
Metadata
- Authors
- Yang, Q., Liu, F., Pan, X. P., Lv, G., Zhang, A., Yu, C. B., & Li, L.
- Affiliations
- First Affiliated Hospital Zhejiang University (CN)
- Corresponding author
- Li, LanJuan
- Venue
- Hepatology International
- Published
- 2010-08-15
- Volume
- 4
- Issue
- 4
- Pages
- 757-761
- ISSN
- 1936-0533 (ISSN-L)
- 1936-0541
- PMC
- PMC2994615
- OpenAlex
- W2151431836
- Cited by
- 22
- References
- 31
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2020: 4 · 2018: 1 · 2017: 2 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 4
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Hepatology International (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Keywords
- porcine endogenous retroviruses, fluidized bed bioreactor, xenotransplantation, biosafety, liver failure, cell culture supernatant, virus transmission
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