title: Bone marrow mononuclear cell therapy for patients with cirrhosis: a Phase 1 study.
abstract: BACKGROUND
  Bone marrow-derived cell therapy has been investigated in patients with severe liver disease.
  
  
  OBJECTIVE
  To assess the feasibility, safety and cell kinetics of autologous bone marrow-derived mononuclear cells (BMMCs) infusion in cirrhotic patients.
  
  
  METHODS
  BMMCs were isolated from autologous bone marrow and 10% of the cells were labelled with (99m)Tc-SnCl₂. Whole body scintigraphy (WBS) was performed 3 and 24 h after infusion via the hepatic artery. Liver function and image were followed during 1 year.
  
  
  RESULTS
  Eight patients received 2.0-15.0 × 10⁸ cells. Three and 24-h WBS showed mean hepatic radiotracer retentions of 41 and 32% respectively. One case of dissection of the hepatic artery and one case of Tako-tsubo syndrome occurred as early complications. A patient developed a cutaneous immunomediated disorder and another patient developed hepatocellular carcinoma (HCC) 12 months after infusion. A reduction in bilirubin was shown at 1 week while serum albumin increased above baseline up to 1 month after infusion (P<0.05).
  
  
  CONCLUSIONS
  BMMCs infusion is feasible and practical in a clinical setting. In vivo tracking of labelled cells demonstrated that the hepatic artery route successfully delivered BMMCs to the liver. The early improvement of laboratory indices of liver function should be interpreted with caution, because this study was not designed to evaluate efficacy. The median Model for End-Stage Liver Disease score had not deteriorated 1 year later. The occurrence of a graft-versus-host disease-like phenomenon highlights the importance of sustained vigilance even when giving autologous cells. Controlled studies are needed to determine whether BMMCs infusion affects HCC development in cirrhosis.
authors.affiliation: Internal Medicine Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bianca G
authors.initials: BG
authors.lastname: Couto
authors.forename: Regina C dos Santos
authors.initials: RC
authors.lastname: Goldenberg
authors.forename: Léa M B
authors.initials: LM
authors.lastname: da Fonseca
authors.forename: James
authors.initials: J
authors.lastname: Thomas
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.forename: Célia M C
authors.initials: CM
authors.lastname: Resende
authors.forename: Feliciano
authors.initials: F
authors.lastname: Azevedo
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Mercante
authors.forename: André L Moreira
authors.initials: AL
authors.lastname: Torres
authors.forename: Henrique S M
authors.initials: HS
authors.lastname: Coelho
authors.forename: Angelo
authors.initials: A
authors.lastname: Maiolino
authors.forename: Alessandra L dos Anjos
authors.initials: AL
authors.lastname: Alves
authors.forename: Juliana V
authors.initials: JV
authors.lastname: Dias
authors.forename: Maria C R
authors.initials: MC
authors.lastname: Moreira
authors.forename: Ana L S B
authors.initials: AL
authors.lastname: Sampaio
authors.forename: Maria A J
authors.initials: MA
authors.lastname: Sousa
authors.forename: Tais H
authors.initials: TH
authors.lastname: Kasai-Brunswick
authors.forename: Sérgio A L
authors.initials: SA
authors.lastname: Souza
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Campos-de-Carvalho
authors.forename: Guilherme F da Motta
authors.initials: GF
authors.lastname: Rezende
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology; D058625:End Stage Liver Disease / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D016896:Treatment Outcome