Ping Li1, Wenjun Zhang1, Lester J Smith2,3, David Ayares4, David K C Cooper5, Burcin Ekser1. 1. Division of Transplant Surgery, Department of Surgery. 2. Radiology and Imaging Sciences. 3. 3D Bioprinting Core, Indiana University School of Medicine, Indianapolis, Indiana. 4. Revivicor Inc., Blacksburg, Virginia. 5. Xenotransplantation Program, Department of Surgery, University of Birmingham at Alabama, Birmingham, Alabama, USA.
Abstract
PURPOSE OF REVIEW: To review the impact of a new technology, 3D-bioprinting, in xenotransplantation research. RECENT FINDINGS: Genetically engineered pigs, beginning with human (h) CD55-transgenic and Gal-knockout pigs, have improved the outcomes of xenotransplantation research. Today, there are more than 30 different genetically engineered pigs either expressing human gene(s) or lacking pig gene(s). CRIPSR/cas9 technology has facilitated the production of multigene pigs (up to nine genes in a single pig), which lack multiple pig xenoantigens, and express human transgenes, such as hCD46, hCD55, hThrombomodulin, hCD39, etc. Although recent studies in nonhuman primates (NHPs) have demonstrated prolonged survival after life-supporting pig kidney, heart, and islet xenotransplantation, researchers have difficulty determining the best genetic combination to test in NHPs because of a potential greater than 100 000 genetic combinations. 3D-bioprinting of genetically engineered pig cells: is superior to 2D in-vitro testing, enables organ-specific testing, helps to understand differences in immunogenicity between organs, and is faster and cheaper than testing in NHPs. Moreover, 3D-bioprinted cells can be continuously perfused in a bioreactor, controlling for all variables, except the studied variable. SUMMARY: 3D-bioprinting can help in the study of the impact of specific genes (human or pig) in xenotransplantation in a rapid, inexpensive, and reliable way.
PURPOSE OF REVIEW: To review the impact of a new technology, 3D-bioprinting, in xenotransplantation research. RECENT FINDINGS: Genetically engineered pigs, beginning with human (h) CD55-transgenic and Gal-knockout pigs, have improved the outcomes of xenotransplantation research. Today, there are more than 30 different genetically engineered pigs either expressing human gene(s) or lacking pig gene(s). CRIPSR/cas9 technology has facilitated the production of multigene pigs (up to nine genes in a single pig), which lack multiple pig xenoantigens, and express human transgenes, such as hCD46, hCD55, hThrombomodulin, hCD39, etc. Although recent studies in nonhuman primates (NHPs) have demonstrated prolonged survival after life-supporting pig kidney, heart, and islet xenotransplantation, researchers have difficulty determining the best genetic combination to test in NHPs because of a potential greater than 100 000 genetic combinations. 3D-bioprinting of genetically engineered pig cells: is superior to 2D in-vitro testing, enables organ-specific testing, helps to understand differences in immunogenicity between organs, and is faster and cheaper than testing in NHPs. Moreover, 3D-bioprinted cells can be continuously perfused in a bioreactor, controlling for all variables, except the studied variable. SUMMARY: 3D-bioprinting can help in the study of the impact of specific genes (human or pig) in xenotransplantation in a rapid, inexpensive, and reliable way.
Authors: Marina Augusto Heuschkel; Amanda Leitolis; João Gabriel Roderjan; Paula Hansen Suss; César Augusto Oleinik Luzia; Francisco Diniz Affonso da Costa; Alejandro Correa; Marco Augusto Stimamiglio Journal: Xenotransplantation Date: 2018-09-28 Impact factor: 3.907
Authors: Raphael P H Meier; Yannick D Muller; Alexandre Balaphas; Philippe Morel; Manuel Pascual; Jörg D Seebach; Leo H Buhler Journal: Transpl Int Date: 2018-01-04 Impact factor: 3.782