Safety Assessment of Autologous Stem Cell Combination Therapy in Patients With Decompensated Liver Cirrhosis: A Pilot Study

Mithun Sharma; Pavan K Pondugala; Shashidhar Jaggaihgari; Sasikala Mitnala; Vemula V Krishna; Ganesh Jaishetwar; Pragati Naik; Pramod Kumar; Anand Kulkarni; Rajesh Gupta; Jagdeesh R Singh; Santosh Darisetty; Anuradha Sekharan; Duvurr N Reddy; Guduru V Rao; Fatima Syeda; Nitin Jagtap; Padaki N Rao

doi:10.1016/j.jceh.2021.03.010

Safety Assessment of Autologous Stem Cell Combination Therapy in Patients With Decompensated Liver Cirrhosis: A Pilot Study

J Clin Exp Hepatol. 2022 Jan-Feb;12(1):80-88. doi: 10.1016/j.jceh.2021.03.010. Epub 2021 Apr 2.

Authors

Mithun Sharma¹, Pavan K Pondugala², Shashidhar Jaggaihgari², Sasikala Mitnala², Vemula V Krishna², Ganesh Jaishetwar³, Pragati Naik¹, Pramod Kumar¹, Anand Kulkarni¹, Rajesh Gupta¹, Jagdeesh R Singh¹, Santosh Darisetty¹, Anuradha Sekharan¹, Duvurr N Reddy¹, Guduru V Rao¹, Fatima Syeda¹, Nitin Jagtap¹, Padaki N Rao¹

Affiliations

¹ Asian Institute of Gastroenterology, Hyderabad, India.
² Asian Healthcare Foundation, Hyderabad, India.
³ Yashoda Hospital, Hyderabad, India.

Abstract

Background: Haematopoietic stem cell (HSC) infusion has demonstrated short-term improvement in liver functions in patients with chronic liver disease. The combination of HSC with mesenchymal stem cells (MSCs), which has an immunomodulatory effect, may augment the effects and enhance the duration of improvements on liver functions. The aim of the present study was to assess the safety of infusing the combination of autologous HSCs and MSCs in decompensated liver cirrhosis.

Methods: In phase I of the study, in vitro assessment was performed to observe the effect of coculturing MSCs with HSCs on their viability and cytokine profiles. Phase II of the study was to assess the safety of combination of stem cell infusions. Bone marrow (50 ml) was aspirated for MSC isolation and expansion using standard protocol. Patients received subcutaneous doses (n = 5) of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization followed by leukapheresis for harvesting HSCs using CliniMacs. HSCs and MSCs were infused through the hepatic artery under fluoroscopic guidance and were monitored for any adverse effects.

Results: In vitro studies revealed 94% viable HSCs in coculture similar to monoculture. HSCs released only interleukin (IL)-8, whereas MSCs secreted IL-8 and IL-6 in monocultures, and both IL-8 and IL-6 were secreted in coculture. G-CSF administration- and bone marrow aspiration-related complications were not observed. Infusion of the cells through the hepatic artery was safe, and no postprocedural complications were noted.

Conclusion: The combination of autologous HSC and MSC infusion is a safe procedure in patients with decompensated liver cirrhosis, and the outcomes needed to be assessed in larger studies.

Trial number: NCT04243681.

Keywords: 7-AAD, 7-aminoactinomycin D; AFP, alpha-fetoprotein; CBA, cytokine cytometric bead assay; CLD, chronic liver disease; DMEM-KO, Dulbecco's modified Eagle's Knock out medium; FBS, foetal bovine serum; G-CSF, granulocyte colony-stimulating factor; HSC, haematopoietic stem cell; IL, interleukin; MELD, Model for End-Stage Liver Disease; MNC, mononuclear cell; MSC, mesenchymal stem cell; SOP, standard operating procedure; TJLB, transjugular liver biopsy; USG, ultrasonography; cath-lab, cardiac catheterization laboratory; cirrhosis of liver; combination of stem cells; mesenchymal stem cells; stem cells.

Associated data

ClinicalTrials.gov/NCT04243681