Autologous Infusion of Expanded Mobilized Adult Bone... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

ORIGINAL CONTRIBUTION: LIVER AND BILIARY TRACT: Editorial

Autologous Infusion of Expanded Mobilized Adult Bone Marrow-Derived CD34+ Cells Into Patients With Alcoholic Liver Cirrhosis

Pai, Madhava M.S., M.R.C.S.1; Zacharoulis, Dimitris M.D.2; Milicevic, Miroslav N. M.D., Ph.D.3; Helmy, Salah M.D.1; Jiao, Long R. M.D., F.R.C.S.1; Levičar, Nataša Ph.D.1; Tait, Paul M.A., F.R.C.R.1; Scott, Michael Ph.D.4; Marley, Stephen B. Ph.D.1; Jestice, Kevin M.Sc.4; Glibetic, Maria Ph.D.3; Bansi, Devinder D.M., F.R.C.P.1; Khan, Shahid A. Ph.D., M.R.C.P.1; Kyriakou, Despina M.D.2; Rountas, Christos M.D.2; Thillainayagam, Andrew M.D., F.R.C.P.1; Nicholls, Joanna P. M.Sc.1; Jensen, Steen M.D.1; Apperley, Jane F. M.D., F.R.C.P.1; Gordon, Myrtle Y. Ph.D., D.Sc.1; Habib, Nagy A. Ch.M., F.R.C.S.1

1Departments of Surgery, Hepatology, Haematology, and Radiology at Hammersmith Campus, Imperial College, London, United Kingdom; 2Larissa Hospital, University of Thessaly, Larissa, Greece; 3Institute of Digestive Diseases, University of Belgrade, Belgrade, Serbia; and 4Addenbrookes Hospital, Cambridge, United Kingdom

Reprint requests and correspondence: Nagy Habib, Ch.M., F.R.C.S., Faculty of Medicine, Hammersmith Campus, Imperial College, Du Cane Road, London W12 0NN, United Kingdom.

CONFLICT OF INTEREST

Guarantor of the article: Nagy A. Habib.

Specific author contributions: All authors actively participated in the study and read the manuscript. Madhava Pai: patient identification, data collection, statistical analysis, clinical consultation (study population), and writing; Dimitris Zacharoulis, Miroslav N. Milicevic, and Maria Glibetic: patient identification, data collection, and clinical consultation (study population); Salah Helmy and Steen Jensen: study design and data collection; Long R. Jiao and Paul Tait: study design and clinical consultation (study population); Natasa Levicar: study design and manuscript preparation; Michael Scott, Stephen B. Marley, and Kevin Jestice: study design and in vitro cell expansion; Andrew Thillainayagam, Devinder Bansi, Shahid A. Khan, Despina Kyriakou, and Christos Rountas: patient identification and clinical consultation (study population); Joanna P. Nicholls and Myrtle Y. Gordon: study design, patient identification, data collection, and manuscript preparation; Jane F. Apperley: study design and leukapheresis; Nagy A. Habib: study design, patient identification, clinical consultation (study population), and manuscript preparation.

Financial support: The study was supported by OmniCyte Ltd.

Potential competing interests: Nagy A. Habib and Myrtle Y. Gordon have financial interest in OmniCyte Ltd.

Received September 13, 2007; accepted February 11, 2008.

Abstract

OBJECTIVES

Recent advances in regenerative medicine, including hematopoietic stem cell (HSC) transplantation, have brought hope for patients with severe alcoholic liver cirrhosis (ALC). The aim of this study was to assess the safety and efficacy of administering autologous expanded mobilized adult progenitor CD34+ cells into the hepatic artery of ALC patients and the potential improvement in the liver function.

METHODS

Nine patients with biopsy-proven ALC, who had abstained from alcohol for at least 6 months, were recruited into the study. Following granulocyte colony-stimulating factor (G-CSF) mobilization and leukapheresis, the autologous CD34+ cells were expanded in vitro and injected into the hepatic artery. All patients were monitored for side effects, toxicities, and changes in the clinical, hematological, and biochemical parameters.

RESULTS

On average, a five-fold expansion in cell number was achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 × 108 pre infusion. All patients tolerated the procedure well, and there were no treatment-related side effects or toxicities observed. There were significant decreases in serum bilirubin (P < 0.05) 4, 8, and 12 wk post infusion. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement through the study period and were significant (P < 0.05) 1 wk post infusion. The Child-Pugh score improved in 7 out of 9 patients, while 5 patients had improvement in ascites on imaging.

CONCLUSION

It is safe to mobilize, expand, and reinfuse autologous CD34+ cells in patients with ALC. The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials.