ES cells to Hepatocytes

Bethesda MD -

Readers of StemCellPatents.com are familiar with the patent of Loren Field which teaches that tissue-specific promoters can drive expression of markers from embryonic stem cell cultures so as to be able to selectively "fish out" stem cells that are starting to commit to a specific lineage.

In a recent paper (Heo J et al. Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver. Hepatology. 2006 Nov 28;44(6):1478-1486) this technique was used to extract cells from embryoid bodies that differentiate into hepatic stem cells. Specifically, since the liver constitutively has the albumin promoter turned on, the scientists transfected mouse embryonic stem cells with a construct that transcribes GFP when the albumin promoter is on, therefore the only cells expressing GFP would be committed to the hepatocyte lineage.

The scientists showed that the initial cells committed to the hepatocyte lineage were detected in close proximity to "beating" myocytes after 7 days of culture. By 28 days the hepatocyte committed cells represented more than 30% of cells isolated from embryoid body culture. When these cells are purified using flow cytometry, they were able to interact with normal liver cells in vivo and accelerated healing after liver injury.

The technique used here can be applied for generation of many tissues from embryoid bodies. We wonder if it has been used for CD34 promoter for generation of hematopoietic stem cells. This would particularly be applicable to scientists trying to use ES-derived hematopoietic stem cells in the clinic.