44 www.bsmiab.org/jabet Purwanto et al., J Adv Biotechnol Exp Ther. 2024 Jan; 7(1): 44-52 INTRODUCTION Cholestasis is a clinical syndrome caused by reduced bile secretion from liver cells, impaired bile secretion at the cholangiocyte level, obstruction of bile flow by stones (cholelithiasis), or tumor masses. When bile formation or excretion occurs, accumulation of biliary constituents will exceed liver's normal cellular architecture, contributing to liver parenchyma cellular damage. Cirrhosis is the final stage of chronic and progressive liver disease caused by infection, autoimmune disorders, biliary obstruction, and metabolic disorders. Globally, cirrhosis is ranked 15 th as a cause of morbidity and 11 th as a leading cause of mortality [1]. Definitive therapy for cirrhosis is liver transplantation, but it takes time to find a matched donor, and thus, patients have to wait relatively for a long time and should continue to use urso deoxy cholic acid (UDCA) as an effort to slow the disease progression [2, 3]. However, studies have found that UDCA can inhibit DNA repair mediated by poly (ADP-ribose) polymerase, thereby interfering with the effectiveness of regeneration of the damaged cells. Therefore, alternative medical therapy that can stimulate liver regeneration is needed. Human mesenchymal stem cells (HuMSC) have low immunogenicity, self-renewal, and are easy to obtain, making it a promising therapy for liver regeneration [4]. HuMSC- *Corresponding author Neni Susilaningsih Department of Anatomy Histology, Faculty of Medicine, Diponegoro University, Semarang, Indonesia Email: nsusilaningsih@gmail.com Academic editor Md Jamal Uddin, PhD ABEx Bio-Research Center, Dhaka, Bangladesh Article info Received: 03 August 2023 Accepted: 19 October 2023 Published: 25 October 2023 Keywords Apoptotisis, Capsase-3, Cholestasis, Mesenchymal stem cells, Secretome, Hepatocytes Copyright: © by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution License (CC BY-4.0). Human mesenchymal stem cell secretome lowers caspase-3 levels and apoptosis in hepatocytes of cholestatic rats Naufal Faruq Purwanto 1 , Neni Susilaningsih 2, * , Bernardus Parish Budiono 3 , Nani Maharani 4 , Ignatius Riwanto 3 1 Faculty of Medicine, Diponegoro University, Semarang, Indonesia 2 Department of Anatomy Histology, Faculty of Medicine, Diponegoro University, Semarang, Indonesia 3 Department of Digestive Surgery, Dr Kariadi General Hospital / Faculty of Medicine, Diponegoro University, Semarang, Indonesia 4 Department of Pharmacology and Therapeutic, Faculty of Medicine, Diponegoro University, Semarang, Indonesia ABSTRACT Liver cirrhosis is a major cause of morbidity and mortality in the world. Definitive therapy is liver transplantation, but it is constrained by difficulties in finding a transplant donor. Human mesenchymal stem cell-based therapy can help liver regeneration directly, through hepatogenic differentiation, or indirectly through the paracrine secretome. Thus, this study aims to determine the effect of Human mesenchymal stem cell secretome (HuMSC-S) administration on caspase 3 levels and apoptotic hepatic cells in a rat model with cholestasis after choledochal duct ligation receiving urso deoxy cholic acid (UDCA). Twenty-four male Wistar rats were subjected to a choledochal duct ligation and were included in this randomized experimental study. After surgical intervention, all rats were randomly assigned into 4 group: control, UDCA, HuMSC-S, and a combination of UDCA and HuMSC-S for 4 weeks. Caspase-3 levels were assessed from the blood sample, while the apoptosis of hepatocytes was evaluated using histopathologic examination of the liver. Interestingly, caspase-3 level was significantly lower in the UDCA and HuMSC-S-treated groups compared to the UDCA or HuMSC-S alone. Similarly, the apoptosis of hepatocyte was significantly lower in the combination group compared to the UDCA or HuMSC-S alone. In conclusion, addition of HuMSC-S to UDCA lowered caspase-3 levels and apoptotic cell count in rats with hepatic cholestasis after choledochal duct ligation. ORIGINAL ARTICLE J Adv Biotechnol Exp Ther. 2024 Jan; 7(1): 44-52 eISSN: 2616-4760, https://doi.org/10.5455/jabet.2024.d04 Published by www.bsmiab.org