Hepatocytic Differentiated Mesenchymal Stem Cells for Translational Research in the Pig

Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Mesenchymal stem cells (MSC) differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical application requires pre-clinical approvals in large animals. Therefore, we characterized porcine MSC from adipose tissue and bone marrow and their hepatocyte differentiation potential for functional liver support after surgical intervention in the porcine model.

Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow-cytometry. Morphology and functional properties (urea-, glycogen synthesis, cytochrome activity) were determined during differentiation and compared with primary-porcine-hepatocytes.

MSC from adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105. MSC displayed differentiation into osteogenic and adipogenic lineage. After differentiation, expression of CD105 decreased and cells adopted the typical morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased during differentiation and was higher in hepatocyte-like cells generated from bone marrow as from adipose tissue.

The hepatocyte differentiation of porcine adipose tissue-derived MSC was shown for the very first time yielding hepatocyte-like cells with specific functions similar in bone marrow and subcutaneous adipose tissue-derived MSC. That makes them good pre-clinical candidates for supportive approaches after liver resection in the pig.