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

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.