# Interspecies Blastocyst Complementation and the Genesis of Chimeric Solid Human Organs

## TL;DR

Scientists are exploring using interspecies blastocyst complementation to grow human organs in animals to address the donor organ shortage.

## Contribution

This paper reviews 19 studies on blastocyst complementation, highlighting progress and challenges in generating chimeric human organs.

## Key findings

- Blastocyst complementation has shown promise in generating organs like the liver, lung, and kidney in chimeric models.
- Only one study used human donor cells in a pig host, while others used rat–mouse chimeras.
- Key challenges include developmental mismatches and ethical concerns about human–animal chimeras.

## Abstract

Solid organ transplantation remains a life-saving treatment for patients worldwide. Unfortunately, the supply of donor organs cannot meet the current need, making the search for alternative sources even more essential. Xenotransplantation using sophisticated genetic engineering techniques to delete and overexpress specific genes in the donor animal has been investigated as a possible option. However, the use of exogenous tissue presents another host of obstacles, particularly regarding organ rejection. Given these limitations, interspecies blastocyst complementation in combination with precise gene knockouts presents a unique, promising pathway for the transplant organ shortage. In recent years, great advancements have been made in the field, with encouraging results in producing a donor-derived organ in a chimeric host. That said, one of the major barriers to successful interspecies chimerism is the mismatch in the developmental stages of the donor and the host cells in the chimeric embryo. Another major barrier to successful chimerism is the mismatch in the developmental speeds between the donor and host cells in the chimeric embryos. This review outlines 19 studies in which blastocyst complementation was used to generate solid organs. In particular, the genesis of the liver, lung, kidney, pancreas, heart, thyroid, thymus and parathyroids was investigated. Of the 19 studies, 7 included an interspecies model. Of the 7, one was completed using human donor cells in a pig host, and all others were rat–mouse chimeras. While very promising results have been demonstrated, with great advancements in the field, several challenges continue to persist. In particular, successful chimerism, organ generation and donor contribution, synchronized donor–host development, as well as ethical concerns regarding human–animal chimeras remain important aspects that will need to be addressed in future research.