Human fibroblast-derived hepatocytesMILAD REZVANIScientists have differentiated human induced pluripotent stem cells (iPSCs) into hepatocytes in a dish, but faced challenges using these cells therapeutically. Most iPSC-derived liver cells do not adequately proliferate after transplantation or function exactly like adult hepatocytes do. Now, researchers from the University of California, San Francisco (UCSF), have differentiated human hepatocytes with a modified technique that bypasses pluripotency, and used these cells to repopulate a mouse liver. Their work was published in Nature today (February 23).
“I really like this paper. It’s a step forward in the field,” said Alejandro Soto-Gutiérrez, an assistant professor of pathology from the University of Pittsburgh, who was not involved in the work. “The concept is reprogramming, but with a shortcut, which is really cool.”
The team isolated human fibroblasts and transduced them with retroviruses expressing three stemness factors: OCT4, SOX2, and KLF4. The researchers grew the transduced cells in the presence of growth factors and small molecules to encourage reprogramming into endoderm. “We divert the cells on their path to pluripotency,” explained coauthor Holger Willenbring, an associate professor of surgery at UCSF. “We still take advantage of what is intrinsic to reprogramming, that the cells are becoming very plastic; they’ve become flexible in what kind ...
