Interspecies chimeras as a platform for exogenic organ production and transplantation

Abstract

Chronic diseases are associated with considerable morbidity and mortality. Therefore, new therapeutic strategies are warranted. Here, we provide a brief review outlining the rationale and feasibility for the generation of intraspecies and interspecies chimeras, which one day may serve as a platform for organ transplantation. These strategies are further associated with consideration of scientific and ethical issues.

Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy

“…BC, with livestock, has attempted to overcome this problem. With newer developments in humanized animal models and an increasingly better understanding of pluripotency across various species, interspecies BC is one of the most promising bioengineering approaches for generating transplantable human organs ( Figure 2A ) ( Garry and Garry, 2021 ).…”

Blastocyst complementation and interspecies chimeras in gene edited pigs

“…The absence of an immunological response by the porcine recipient following blastocyst complementation using GFP-labeled porcine blastomeres supports the notion that tolerance is established in the resulting chimera (Das et al, 2020;Maeng et al, 2021). Future studies will need to dissect the mechanisms (Garry and Garry, 2021).…”

“…These human organs are then harvested and transplanted to the patient. Figure modified from ( Garry and Garry, 2021 ).…”

“…Technological advancements such as gene editing ( Doudna and Charpentier, 2014 ; Jinek et al, 2012 ; Cong et al, 2013 ) and somatic cell nuclear transfer (SCNT) technologies ( Polejaeva et al, 2000 ; Tian et al, 2003 ; Galli and Lazzari, 2021 ) have now allowed for genetic modification of large animals such as the pig ( Lai et al, 2002 ; Yamada et al, 2005 ; Hisashi et al, 2008 ; Pierson et al, 2020 ; Watanabe et al, 2020 ; Hinrichs et al, 2021 ; Reichart et al, 2021 ) ( Figure 1 ). These genetically modified pigs have renewed the interest in xenotransplantation but they also provide a platform for engineering human organs and nonhuman primate cells (interspecies chimeras) in large animals ( Wu et al, 2016 ; Garry and Garry, 2019 ; Fu et al, 2020 ; Garry and Garry, 2021 ). For example, a gene edited pig served as a donor for the first porcine cardiac xenotransplantation which was performed early in 2022 ( Graham, 2022 ; Griffith et al, 2022 ; Shah and Han, 2022 ).…”