Endocrine Abstracts

Human pluripotent stem cells can be generated from embryos at the blastocyst stage (human embryonic stem cells or hESCs) or from reprogrammed somatic cells (human induced pluripotent stem cells or hIPSCs). These cells combine the property to grow indefinitely in vitro and the capacity to differentiate into a broad number of cell types. Thus, human pluripotent cells represent a unique opportunity for regenerative medicine since they could enable to production of infinite quantity of cell types with a clinical interest such as liver and pancreatic cells. Importantly, hIPSCs could allow the production of patient specific cell types which are fully immuno-compatible with the original donor thereby avoiding the use of immune suppressive treatment during cell based therapy. In addition, hIPSCs can be generated from somatic cells isolated from patients with diverse diseases. Then, the resulting ‘diseased’ hIPSCs can be differentiated into the cell type targeted by the disease and thus provide an in vitro model useful for basic studies and drug screening.

Our group has established a solid experience with hIPSCs by deriving more than 200 lines from 20 patients suffering from diverse diseases. For that, we have developed a robust method of reprogramming allowing the derivation of hIPSCs from 8 of 10 patients independently of their age or sex. In addition, we have developed fully defined culture systems to differentiate human pluripotent stem cells into pancreatic and hepatic progenitors. The resulting cells display functional characteristics specific of their in vivo counterparts such as glucose response and albumin secretion. More importantly, this approach can be used with hIPSCs derived from patient with liver metabolic diseases to develop in vitro models allowing large scale experiments impossible to perform with primary culture or biopsy material. These results represent a first step to deliver the clinical benefit of human pluripotent stem cells.