Xenotransplantation: an update on recent progress and future perspectives

Abstract

Currently, the number of patients awaiting transplantation is continuously increasing, and shortage of available deceased organ donors is the major limitation for organ and cell allotransplantation. Research to develop alternative sources of tissues is ongoing and xenogeneic organs or cells represent an attractive solution. This review focuses on recent progress achieved in this field, including the development of newly genetically modified animal donors and new immunosuppressive approaches. As xenotransplantation is moving closer to clinical application, future perspectives must establish guidelines to ensure that future clinical trials are carried out ethically and safely

In vitro isolation of neural precursor cells from the adult pig subventricular zone

“…In the future, production of neural stem/progenitor cells from the adult pig by the presently described procedure is likely to promote cell therapy improvements, first in animal models, but also in clinical attempts to repair neural lesions in adult human. By analogy with other tissues (Bucher et al, 2005;Vodicka et al, 2005), adult pig neural precursor cells should be feasible for transplantation into diseased humans without immune rejection (Armstrong et al, 2001;Yan et al, 2006). The present study thus provides the substratum for an alternative source to human allografts for transplantation in neurodegenerative disorders or injuries, which is now open to experimentation.…”

“…A basic limitation upstream of purported neurological applications is the use of rodent cell cultures for study, since even in vitro neurosphere assay conditions are suspected to vary across species (Reynolds and Rietze, 2005;Ray and Gage, 2006). Regulatory mechanisms should therefore be investigated in neural stem cells from adult humans, or at least, from the most closely related non-primate animal species, which is the pig (Bucher et al, 2005;Vodicka et al, 2005). Pig neural stem cells have only been isolated from the foetal brain to date (Schwartz et al, 2005;Harrower et al, 2006).…”

Precision Editing of Large Animal Genomes

“…Pigs due to similar size and physiology also became the leading candidate for production of tissues and organs for xenotransplantation to humans (Bucher, Morel, & Buhler, 2005). As our knowledge in the molecules and reactions involved in xenograft rejection following tissue and organ transplantation grew, another wave of modifications arose to humanize the cell surface proteins of animals to suppress animal-specific antigens that initiated strong immunological rejections by the immune systems of human recipients (Klymiuk, Aigner, Brem, & Wolf, 2010; Sachs & Galli, 2009).…”

Production of Multiple Transgenic Yucatan Miniature Pigs Expressing Human Complement Regulatory Factors, Human CD55, CD59, and H-Transferase Genes

“…It is mediated by pre-existing natural antibodies against the galactose-α-1,3-galactose (α-Gal) antigen and the activation of a complement cascade [2], [3]. Since Lai and colleagues first reported successful production of α-1,3-galactosyltransferase knockout (GT-KO) cloned pigs by somatic cell nuclear transfer (SCNT) [4], many research groups have developed α-Gal-deficient pigs [5], [6].…”