3차원 세포 프린팅 기술 기반의 간 경변증 치료용 패치 형태의 줄기세포 치료제 개발

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 injection 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 new stem cell delivery method, which is a 3D cell-printed patch-type stem cell therapy (liver patch) with liver decellularized extracellular matrix (LdECM) bioink and human bone marrow derived mesenchymal stem cells (hBMMSCs) to enhance the efficacy and delivery efficiency of stem cell therapy. In the in vitro study, the liver patch showed anti-fibrosis effect in the inactivation of the activated hepatic stellate cell (aHSC) by paracrine effect. For in vivo efficacy assessment, the liver patch was implanted to the pathological liver tissue of irreversible cirrhosis mouse models for 4 weeks. In the liver tissue of liver patch delivered 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 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.