3D Cell-printing of prevascularized stem cell patch for liver cirrhosis treatment

Abstract

Liver cirrhosis is an irreversible liver failure which has no curative therapy except liver transplantation, but it is limited by a donor shortage. Stem cell transplantation has been regarded as an alternative therapy to the liver transplantation; yet, the delivery efficiency of stem cells and the efficacy are still controversy. Therefore, we developed a novel stem cell therapy, which is a hBMMSC (human bone marrow derived mesenchymal stem cell) / EPC (endothelial progenitor cell)-laden prevascularized stem cell patch using 3D cell-printing technology with liver decellularized extracellular matrix (LdECM) bioink to enhance the efficacy and delivery efficiency of stem cell therapy. In the in vitro study, the prevascularized stem cell patch showed anti-fibrotic effect on the activated hepatic stellate cell (aHSC) by paracrine effect. For in vivo efficacy assessment, the stem cell patch was transplanted to the pathological liver tissue of irreversible cirrhosis mouse models for 4 weeks. In the stem cell patch transplanted cirrhosis model, the hBMMSCs remained much more than the stem cell injected group during implantation, and the deposited endogenous collagen was significantly decreased. Moreover, fibrosis markers were significantly decreased in the stem cell patch delivered cirrhosis model. Consequently, the results demonstrated that the stem cell patch with functional LdECM bioink and stem cell would be an effective therapy for liver cirrhosis treatment.