Advanced Cell Technology, Inc. has reported for the first time a robust and highly efficient process for the generation of high-purity hepatocytes (liver cells).
The research, described online (ahead of print) in the journal STEM CELLS, signifies a significant step towards the efficient generation of hepatocytes for use in regenerative medicine and drug discovery. Moreover, the research represents another one of Advanced Cell Technology ' s efforts aimed at the large-scale differentiation of human embryonic stem cells (hESCs) into critical replacement cell types. In addition to demonstrating the efficient generation of hepatocytes in research published today, the company has made significant progress in the generation of retinal pigmented epithelial (RPE) cells to treat retinal degenerative diseases and the generation of hemangioblasts to treat vascular disease as well as to create a large-scale and donorless source of red blood cells and platelets.
Two hallmarks of embryonic stem cells, their versatility and capacity for unlimited self renewal, suggest the cells could serve as a potentially inexhaustible source of cells for replacement therapy. As with other tissues, there is a scarcity of donor livers and hepatocytes, which is compounded by the low recovery and proliferative capacity of adult hepatocytes. In addition to the cells ' potential use for the treatment of liver disease, hESC-derived hepatocytes could also provide a valuable model for novel pharmaceutical drug discovery assays as well as new drug metabolism and cytotoxicity screens, particularly because the liver is a major site for detoxification.
“ We have established a highly-efficient method for deriving hepatocytes from stem cells that mirrors events in embryonic development, ” said Robert Lanza, M.D., Chief Scientific Officer at Advanced Cell Technology, Inc. and senior author of the study. “ Large scale production of hepatocytes using this method should greatly bolster their applications in basic research, clinical medicine and preclinical drug discovery. ”
The method reported yielded synchronous populations of hepatocytes that were generated in clinically preferred conditions with minimum use of serum and cell feeders. Highly enriched populations of definitive endoderm (DE) were generated from hESCs and then induced to differentiate along the hepatic lineage by the sequential addition of inducing factors implicated in physiological hepatogenesis. The differentiation process was largely uniform with cell cultures progressively expressing increasing numbers of hepatic lineage markers. The hepatocytes exhibited functional hepatic characteristics such as glycogen storage, indocyanine green uptake and release, and albumin secretion. In an animal model of acute liver injury, the hESC-DE cells differentiated into hepatocytes and successfully repopulated the damaged liver.
“ I am delighted with the tremendous progress our scientists are making to generate a variety of important functional cells types and refine our cell differentiation process, ” stated William M. Caldwell IV, CEO and Chairman of Advanced Cell Technology. “ These cells have the potential to benefit many Americans suffering from serious and potentially life-threatening diseases with few if any alternatives. We are committed to developing new methods to help translate our stem cell technology into the clinic and are seeking partners for some of our newest scientific advances. ”
Other authors on the paper were Dr. Sadhana Agawal (first author of the study) and Katherine Holton, a senior research associate at Advanced Cell Technology, Inc.