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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 × 104/kg up to 1 × 106/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.

Original languageEnglish
Pages (from-to)1059-1066
Number of pages8
JournalDigestive and Liver Disease
Volume47
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

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Clinical Trials, Phase I
End Stage Liver Disease
Stem Cells
Bone Marrow
Leukapheresis
Liver Regeneration
Liver
Hepatic Artery
Liver Failure
Granulocyte Colony-Stimulating Factor
Cell- and Tissue-Based Therapy
Bone Marrow Cells
Liver Transplantation

Keywords

  • Cirrhosis
  • Haematopoietic stem/progenitor cells
  • Regenerative medicine
  • Stem cell therapy

ASJC Scopus subject areas

  • Medicine(all)
  • Hepatology
  • Gastroenterology

Cite this

Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease : A phase I clinical trial. / Andreone, Pietro; Catani, Lucia; Margini, Cristina; Brodosi, Lucia; Lorenzini, Stefania; Sollazzo, Daria; Nicolini, Benedetta; Giordano, Rosaria; Montemurro, Tiziana; Rizzi, Simonetta; Dan, Elisa; Giudice, Valeria; Viganò, Mariele; Casadei, Andrea; Foschi, Francesco G.; Malvi, Deborah; Bernardi, Mauro; Conti, Fabio; Lemoli, Roberto M.

In: Digestive and Liver Disease, Vol. 47, No. 12, 01.12.2015, p. 1059-1066.

Research output: Contribution to journalArticle

Andreone, P, Catani, L, Margini, C, Brodosi, L, Lorenzini, S, Sollazzo, D, Nicolini, B, Giordano, R, Montemurro, T, Rizzi, S, Dan, E, Giudice, V, Viganò, M, Casadei, A, Foschi, FG, Malvi, D, Bernardi, M, Conti, F & Lemoli, RM 2015, 'Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease: A phase I clinical trial', Digestive and Liver Disease, vol. 47, no. 12, pp. 1059-1066. https://doi.org/10.1016/j.dld.2015.08.018
Andreone, Pietro ; Catani, Lucia ; Margini, Cristina ; Brodosi, Lucia ; Lorenzini, Stefania ; Sollazzo, Daria ; Nicolini, Benedetta ; Giordano, Rosaria ; Montemurro, Tiziana ; Rizzi, Simonetta ; Dan, Elisa ; Giudice, Valeria ; Viganò, Mariele ; Casadei, Andrea ; Foschi, Francesco G. ; Malvi, Deborah ; Bernardi, Mauro ; Conti, Fabio ; Lemoli, Roberto M. / Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease : A phase I clinical trial. In: Digestive and Liver Disease. 2015 ; Vol. 47, No. 12. pp. 1059-1066.
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T1 - Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease

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AU - Andreone, Pietro

AU - Catani, Lucia

AU - Margini, Cristina

AU - Brodosi, Lucia

AU - Lorenzini, Stefania

AU - Sollazzo, Daria

AU - Nicolini, Benedetta

AU - Giordano, Rosaria

AU - Montemurro, Tiziana

AU - Rizzi, Simonetta

AU - Dan, Elisa

AU - Giudice, Valeria

AU - Viganò, Mariele

AU - Casadei, Andrea

AU - Foschi, Francesco G.

AU - Malvi, Deborah

AU - Bernardi, Mauro

AU - Conti, Fabio

AU - Lemoli, Roberto M.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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 × 104/kg up to 1 × 106/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.

AB - 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 × 104/kg up to 1 × 106/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.

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KW - Haematopoietic stem/progenitor cells

KW - Regenerative medicine

KW - Stem cell therapy

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