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.
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.
Authors: Andreas Nussler; Sarah Konig; Michael Ott; Etienne Sokal; Bruno Christ; Wolfgang Thasler; Marc Brulport; Geredn Gabelein; Wiebke Schormann; Maren Schulze; Ewa Ellis; Matthias Kraemer; Frank Nocken; Wolfgang Fleig; Michael Manns; Steven C Strom; Jan G Hengstler Journal: J Hepatol Date: 2006-04-27 Impact factor: 25.083
Authors: Maren Ruhnke; Hendrik Ungefroren; Andreas Nussler; Franz Martin; Marc Brulport; Wiebke Schormann; Jan G Hengstler; Wolfram Klapper; Karin Ulrichs; James A Hutchinson; Bernat Soria; Reza M Parwaresch; Peter Heeckt; Bernd Kremer; Fred Fändrich Journal: Gastroenterology Date: 2005-06 Impact factor: 22.682
Authors: C Schmidt; F Bladt; S Goedecke; V Brinkmann; W Zschiesche; M Sharpe; E Gherardi; C Birchmeier Journal: Nature Date: 1995-02-23 Impact factor: 49.962