Hepatogenic differentiation of mesenchymal stem cells induced by insulin like growth factor-I

To improve hepatic differentiation of human mesenchymal stem cell (MSC) using insulin growth factor 1 (IGF-I), which has important role in liver development, hepatocyte differentiation and function.

Bone marrow of healthy donors was aspirated from the iliac crest. The adherent cells expanded rapidly and were maintained with periodic passages until a relatively homogeneous population was established. The identification of these cells was carried out by immunophenotype analysis and differentiation potential into osteocytes and adipocytes. To effectively induce hepatic differentiation, we designed a protocol based on a combination of IGF-I and liver specific factors (hepatocyte growth factor, oncostatin M and dexamethasone). Morphological features, hepatic functions and cytological staining were assessed to evaluate transdifferentiation of human marrow-derived MSCs.

Flow cytometric analysis and the differentiation potential into osteoblasts and adipocytes showed that more than 90% of human MSCs which were isolated and expanded were positive by specific markers and functional tests. Morphological assessment and evaluation of glycogen storage, albumin and α-feto protein expression, as well as albumin and urea secretion revealed a statistically significant difference between the experimental groups and control.

In vitro differentiated MSCs using IGF-I were able to display advanced liver metabolic functions, supporting the possibility of developing them as potential alternatives to primary hepatocytes.