- Scientists have grown tiny human livers that functioned after transplant into rats.
- Trying to improve transplant numbers and outcomes is a major research area for biologists.
- The scientists began by making "decellularized scaffolds" on which human stem cells were grown into liver cells.
Scientists from the University of Pittsburgh and their colleagues have grown tiny human livers and successfully implanted them into rats. The livers began as stem cells that are cultivated into skin and vascular cells that form a complete microenvironment. “The organ-like microenvironment further matures some liver functions and produces tissue structures similar to those found in human livers,” their paper in Cell Reports explains.
In their summary, the scientists say previous research has mostly used existing structures of rat cells to grow their organlike environments. They explain:
“Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in rats.”
This cutting-edge science begins with human volunteers who gave skin cell samples. These were reverse engineered into stem cells and then redirected to become different needed cells to form a liver. From there, the scientists seeded a “liver scaffold”—a rat-based extracellular matrix (ECM) structure with, miraculously, its cells removed—with their new human liver cells.
“The goal of decellularization is to remove cells while maintaining the structural, mechanical, and biochemical properties of the ECM scaffold,” the researchers explain.
There were traces of DNA left in the rat scaffolds, though. “DNA content, a commonly used marker of decellularization, was 3 [to] 10 times higher than in previous studies, which may lead to an adverse immune response if animal-derived scaffolds are to be used in humans, however, this remains to be tested.”
Inverse reports that while the resulting liver-growing process has taken 10 years to perfect, this batch of miniature livers took under a month to grow—compared with two years in the human body. The team then transplanted the livers into a small group of specially prepared rats, which had their immune systems suppressed to encourage the transplant and their liver lobes removed to encourage regeneration.
Five is a tiny sample, to be sure, but all five livers worked during the four-day experimental period, producing and secreting bile and urea. Some had problems around the graft site, which makes sense for an almost completely human organ transplanted into a rat.
“Harvested human iPSC-liver grafts measure 2.5 [to] 3 [centimeters] and showed liver-like tissue texture,” the scientists say. Despite a handful of understandable problems, they feel optimistic about the future of lab-grown human livers on decellularized scaffolds. They conclude:
“Future studies should concentrate on procedures to allow continued vascular development using, for instance, nanoparticles and growth-factor-hydrogel modification of acellular scaffolds. The strategy shown here represents a significant advance toward our understanding of the production of bioengineered autologous human-liver grafts for transplantation.”
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