Generation of human organs from stem cells in animal hosts

Xabier Aranguren

Centro de Investigación Médica Aplicada (CIMA), Pamplona, Universidad de Navarra, Spain

Organ transplantation has saved the lives of tens of thousands of people in recent decades. It represents the last possible treatment for a significant percentage of diseases that have not responded to previous therapies and ultimately result in organ failure.

However, there is a shortage of organs available for transplantation, making it necessary to seek alternatives to meet the current clinical demand. Every year, thousands of people die while waiting for an organ. The need for organs has led to different approaches being proposed, such as transplanting organs from other species into humans, or creating chimeric organisms to generate human organs in other animals, such as pigs, which are similar in size and characteristics to those of humans.

For a long time, experts have been working on methods of growing healthy organs outside the human body. One such method, known as blastocyst complementation, has already achieved promising results. Researchers take blastocysts (clusters of cells that form several days after egg fertilisation) from animals genetically engineered to be incapable of developing a specific organ, for example the heart, and inject them with pluripotent stem cells from a normal donor, not necessarily from the same species, to grow the desired organ. The new organ retains the characteristics of the original stem cell donor and can therefore potentially be used in transplantation therapy. Extending this approach to pig embryos and human stem cells could allow human organs to be grown in a porcine host.

However, to achieve this goal, the chimeric potential of human stem cells needs to be improved. This improvement constitutes the main objective of this project, which aims to better understand the mechanisms regulating the procurement of chimeras, that is, organisms containing cells with genetic material from two or more different individuals. The knowledge gained will lay the foundations for the future generation of human organs in pigs.

• Francisco Alberto García Vázquez, Universidad de Murcia, Spain

• Graziano Martello, Università degli Studi di Padova, Italy

Generation of humanized organs from human iPS cells

€999,127.90