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

Dig Liver Dis. 2015 Dec;47(12):1059-66. doi: 10.1016/j.dld.2015.08.018. Epub 2015 Sep 10.

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.

Keywords: Cirrhosis; Haematopoietic stem/progenitor cells; Regenerative medicine; Stem cell therapy.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

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