Current Status and Future Perspectives of Xenotransplantation and Stem Cell Research in Transplantation Field

Article information

J Korean Med Assoc. 2008;51(8):732-744
Publication date (electronic) : 2008 August 31
doi : https://doi.org/10.5124/jkma.2008.51.8.732
Department of Microbiology and Immunology, Seoul National University College of Medicine, Korea. chgpark@snu.ac.kr

Abstract

The severe shortage of human organ donors is one of the biggest problems with organ transplantation. The solution for this problem would be development of artificial organs or mechanical devices, stem cell derived organs, and xenogeneic organs. Artificial organs may provide a short term life or functional support, but they cannot be considered as a life-long curative therapeutic modality in the near future. Although considerable efforts have been invested in the production of lab-grown organs using stem cells, clinical application of these organs will demand many years of research and investment. Currently, stem cells are clinically applied in cell replacement therapy. Therefore, xenotransplantation would be the most imminent solution for the organ shortage. Recent advances in our understanding of the mechanisms of xenograft rejection, zoonotic infections including PERV (porcine endogenous retrovirus), and production of α-1,3-galactosyltransferase-deficient pigs, put xenotransplantation closer to the clinical reality. At this stage, pancreatic islet xenotransplantation would be the first target for clinical application, the efficacy of which has been proven in non-human primate study and is waiting for the development of relatively non-toxic or clinically applicable immunosuppressive or tolerance-inducing regimens.

Notes

This study was supported by a grant from the National R & D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea(A040004).

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Article information Continued

Figure 1

SNU miniature swine is breeding to meet the PHS guidelines for xenograft donor in Center for Animal Resource Development at Seoul National University College of Medicine under the qualified specific pathogen free condition. Gnotobiotic condition is established through hysterectomy followed by breeding in germ-free isolator.

Figure 2

Histophathologic finding of AHXR in the pig lung 1 hour post transplantation to to beagle dog. Massive hemorrhage, thrombosis, edema and infiltration of inflammatory cells were observed. As both pig and dog express α1,3-Gal antigen, the antibody mediated rejection could be caused by anti-non-Gal antibodies.

Table 1

Replacement of donor organ shortage (1)

Table 1

Table 2

Diseases theoretically curable with stem cells therapy in USA (2)

Table 2

Table 3

Regenerative medicine capabilities (according to International Foundation for Regenerative Medicine GmbH)

Table 3