Development of 3D Cell Printed Patch-Type Stem Cell Therapy for Treatment of Liver Cirrhosis

Abstract

Liver cirrhosis is an irreversible end-stage liver disease which has no effective therapy except for liver transplantation, but donor shortage has been a critical limitation. Stem cell injection has been regarded as an alternative to the liver transplantation; yet, there is no optimal condition for such therapy. Moreover, the efficiency of delivery is below 10%, and the efficacy is reported to be minimal or even none. Therefore, we developed a liver patch, which is a 3D cell printed patch-type stem cell therapy with liver decellularized extracellular matrix (LdECM) bioink and human bone marrow derived mesenchymal stem cell to enhance the efficacy and delivery efficiency. The liver patch showed in vitro efficacy in the inactivation of the activated hepatic stellate cell (aHSC) by paracrine effect in transwell coculture condition. For in vivo efficacy assessment, the liver patch was implanted to the pathological liver tissue of irreversible cirrhosis mouse models. The deposited endogenous collagen was significantly decreased, and aHSCs were inactivated in the liver patch delivered cirrhosis model. Consequently, the results demonstrated that the liver patch with functional LdECM bioink and stem cell would be an effective therapy for liver cirrhosis treatment.