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Review
. 2024 Aug;54(8):829-838.
doi: 10.1007/s00595-024-02861-7. Epub 2024 May 11.

How should cardiac xenotransplantation be initiated in Japan?

Shunsuke Saito  1 , Shuji Miyagawa  2 , Takuji Kawamura  3 , Daisuke Yoshioka  3 , Masashi Kawamura  3 , Ai Kawamura  3 , Yusuke Misumi  3 , Takura Taguchi, Takashi Yamauchi  3 , Shigeru Miyagawa  3
Affiliations
Review

How should cardiac xenotransplantation be initiated in Japan?

Shunsuke Saito et al. Surg Today. 2024 Aug.

Abstract

The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies.

Keywords: Cardiac xenotransplantation; End-stage heart failure; Genetic engineering; Hyperacute rejection; Pig.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Between January, 2010 and July, 2022, a total of 133 patients required temporary mechanical circulatory support at Osaka University Hospital. Of these 133 patients, 35 were not candidates for human allotransplantation or left ventricular assist devices as destination therapy and could not be weaned off mechanical support. The clinical outcomes of these 35 patients were poor; however, such patients are possible candidates for cardiac xenotransplantation. HTx heart transplantation with human hearts, MCS mechanical circulatory support
Fig. 2
Fig. 2
Somatic cell cloning is a technique in which the nuclei of cultured somatic cells are implanted into the cytoplasm of unfertilized eggs to create cloned embryos, and cloned individuals are born through a borrowed abdominal pregnancy. By applying procedures such as gene transfer or gene knockout to cultured somatic cells, genetically modified cell nuclei can be obtained. Using such nuclei to create cloned embryos leading to cloned individuals, a theoretically unlimited number of genetically modified individuals can be produced as required
See this image and copyright information in PMC

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