In vivo construction of liver tissue by implantation of a hepatic non-parenchymal/adipose-derived stem cell sheet.

Subcutaneous hepatocyte sheet implantation is an attractive therapeutic option for various liver diseases. However, this technique is limited by the availability of hepatocytes. Thus, the use of hepatic non-parenchymal cells (NPCs) containing small hepatocytes, which have the ability to proliferate more rapidly than mature hepatocytes, for transplantation has been suggested. The aim of our study was to construct liver tissue subcutaneously in rats by implanting NPC sheets co-cultivated with adipose-derived stem cells (ADSCs), which produce certain angiogenic factors. We crafted NPC-ADSC sheets on temperature-responsive culture dishes. NPCs formed functioning bile canaliculi and stored glycogen. In addition, their ability to produce albumin was not inferior to that of hepatocytes. Albumin production increased over time when co-cultivated with ADSCs. We then implanted the co-cultivated cell sheets subcutaneously. The co-cultivated sheets retained glycogen, formed bile canaliculi, showed signs of vascularization and survived subcutaneously without pre-vascularization. These results suggest that NPCs can be a viable option in cell therapy for liver diseases. This technique using co-cultivated cell sheets may be useful in the field of regenerative medicine.