Making livers in the lab

Author: Katie Moisse, 11/05/10

In 2009, surgeons transplanted 2,155 organs — nearly a quarter of which were livers – from live or deceased donors into grateful recipients. Sadly, another 3,796 Canadians remained on the transplant wait list, and 249 died while waiting, according to the Canadian Organ Replacement Register.

To help mitigate the organ donor shortage, scientists are looking for ways to create bioartificial organs by seeding human cells onto transplantable tissue scaffolds. For the first time, researchers have generated functional mini-livers by growing primary human fetal liver progenitor cells and endothelial cells on a decellularized liver scaffold — the skeleton of a liver, complete with connective tissue and blood vessels — from a ferret.

The researchers, from Wake Forest University in Winston-Salem, North Carolina, fed the human cells (70 million human liver progenitor cells and 30 million endothelial cells) into the ferret liver bioscaffold through the portal vein and placed the hybrid organoid in a bioreactor constantly perfused with fresh culture medium for a week. The cells seeded in multiple, thick clusters throughout the bioscaffold and began to function like liver tissue, expressing albumin and a host of other liver cell markers. Lead author Pedro Baptista presented the team’s preliminary findings October 30 at The Liver Meeting (formerly the American Association for the Study of Liver Diseases annual meeting) in Boston.

Another research team, from Massachusetts General Hospital, Harvard Medical School and Shriners Hospitals for Children in Boston, used a similar approach to reconstitute a decellularized rat liver with adult rat hepatocytes and endothelial cells, with the ultimate goal of transplanting a functional bioengineered organ into a rat. However, neither group was able to repopulate more than a third of the bioscaffold with cells.

Using decellularized tissue to engineer organs in vitro has tremendous potential though, because it allows scientists to take advantage of the organ’s existing, often complex vasculature. Furthermore, in the absence of cells, organs’ skeletons are relatively non-immunogenic. This means, for instance, that decellularized pig livers seeded with human cells could potentially bypass the organ rejection problems linked to xenotransplantation (interspecies transplantation). In the meantime, getting more cells to seed onto these organ scaffolds, fostering their ability to function like proper organs and nursing their ability to withstand the transplant process and survive long-term are goals more realistic than ever.

 

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