The HepaRG™ origins cells were isolated from a donor with cholangiocarcinoma, and the novelty of the work performed by INSERM and Biopredic International scientists was to recognize their uniqueness and determine optimum culture conditions to support either growth or function as differentiated, adult hepatic cells.
Thus, we have not interfered with their genome but utilized it advantageously, which may account for the cells’ karyotypic stability over a number of passages. The use of proliferating cells can provide a unique opportunity to analyze signaling pathways and elucidate control mechanisms in the HepaRG™.
Our scientists’ excitement grew as they realized that the HepaRG™ cells carried properties of early hepatic progenitor cells as well as mature hepatocytes, each condition allowing for uses of the cells that are unmatched by any other hepatic cell model. For example, HepaRG™ in the growth state tolerate infection by certain viruses which rarely enter differentiated, adult hepatocytes.
The predictability with which the cells can be differentiated, means that we can reliably provide cells with consistent characteristics at lower cost than primary human hepatocytes.
Scientists can utilize HepaRG™ in two forms: cryopreserved, differentiated cells that are convenient to both use and store; and growth-stage cells that can be grown in-house to build stock populations and then frozen or differentiated.
Biopredic International has complete user instructions to ensure maximum quality of the differentiated cells, which require non-expensive materials for their use. In fact, HepaRG™ cells actually reduce overall costs compared with cryopreserved primary human hepatocytes.
When using growth-stage cells, a common question is whether their stability and useful life are retained when they are differentiated, and with HepaRG™, the answers are positive.
They can be grown and split passages eight times when used according to our recommended protocols and medium supplements (the base medium is off-the-shelf William's E medium). The differentiation process is the same across passages and cells are usable for at least four weeks once differentiation is achieved.
Since the HepaRG™ have not undergone transfection or genome modification, they retain a range of hepatic cell responses, meaning that they have a very broad application versatility. For instance, they have shown the propensity to develop cholestasis or steatosis when exposed to appropriate agents. Likewise, they have been used successfully in studies investigating sugar and lipid metabolism, in-vivo engraftment in rodents, 3D systems, bioartificial livers, chronic toxicity, etc.
Most importantly, Biopredic International maintains a large supply of HepaRG™ progenitor cells to serve as seed stock. This is sufficient to meet the needs of the next decade, even if growth in demand is triple our projections.