Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease: A phase I clinical trial.

Abstract

BACKGROUND:

Bone marrow stem/progenitor cells seem to be effective in liver regeneration after tissue injury.

AIM:

To evaluate the feasibility and safety of the mobilization and reinfusion of CD133+ stem/progenitor cells in patients with end-stage liver disease.

METHODS:

Autologous CD133+ stem/progenitor cells, mobilized with granulocyte-colony stimulating factor, were collected by leukapheresis and reinfused at increasing doses through the hepatic artery starting from 5×10(4)/kg up to 1×10(6)/kg.

RESULTS:

16 subjects with Model for End-stage Liver Disease (MELD) score between 17 and 25 were enrolled, 14 mobilized an adequate number of CD133+ stem/progenitor cells and 12 were reinfused. No severe adverse events related to the procedure were reported. MELD score significantly worsened during mobilization in Child Turcotte Pugh-C patients. A significant improvement of liver function was observed 2 months after reinfusion (MELD 19.5 vs. 16; P=0.045). Overall, 5 patients underwent liver transplantation within 12 months from reinfusion and 2 died because of progressive liver failure.

CONCLUSIONS:

CD133+ stem/progenitor cells reinfusion in patients with end-stage liver disease is feasible and safe. A worsening of liver function was observed during mobilization in Child Turcotte Pugh-C patients. The temporary improvement of MELD score after reinfusion suggests that stem cells therapy may be a "bridge to transplant" approach for these patients.

• Authors: Pietro Andreone, Lucia Catani, Cristina Margini, Lucia Brodosi, Stefania Lorenzini, Daria Sollazzo, Benedetta Nicolini, Rosaria Giordano, Tiziana Montemurro, Simonetta Rizzi, Elisa Dan, Valeria Giudice, Mariele Viganò, Andrea Casadei, Francesco G Foschi, Deborah Malvi, Mauro Bernardi, Fabio Conti, Roberto M Lemoli
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 47 Issue 12 Pg. 1059-66 (Dec 2015) ISSN: 1878-3562 [Electronic] Netherlands
• PMID: 26427587 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chemical References

• AC133 Antigen
• Antigens, CD
• Glycoproteins
• PROM1 protein, human
• Peptides
• Granulocyte Colony-Stimulating Factor

Topics

• AC133 Antigen
• Adult
• Aged
• Antigens, CD
• Case-Control Studies
• End Stage Liver Disease (therapy)
• Female
• Glycoproteins
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Hematopoietic Stem Cell Mobilization
• Hematopoietic Stem Cell Transplantation
• Humans
• Italy
• Leukapheresis
• Liver Function Tests
• Male
• Middle Aged
• Peptides
• Prospective Studies
• Stem Cells (cytology)