TY - JOUR
T1 - Bone marrow mononuclear cell therapy for patients with cirrhosis: a Phase 1 study
AU - Couto, Bianca G.
AU - dos Santos Goldenberg, Regina C.
AU - da Fonseca, Lea M. B.
AU - Thomas, James
AU - Gutfilen, Bianca
AU - Resende, Celia M. C.
AU - Azevedo, Feliciano
AU - Mercante, Daniel R.
AU - Moreira Torres, Andre L.
AU - Coelho, Henrique S. M.
AU - Maiolino, Angelo
AU - dos Anjos Alves, Alessandra L.
AU - Dias, Juliana V.
AU - Moreira, Maria C. R.
AU - Sampaio, Ana L. S. B.
AU - Sousa, Maria A. J.
AU - Kasai-Brunswick, Tais H.
AU - Souza, Sergio A. L.
AU - Campos-de-Carvalho, Antonio C.
AU - da Motta Rezende, Guilherme F.
PY - 2011/3
Y1 - 2011/3
N2 - BackgroundBone marrow-derived cell therapy has been investigated in patients with severe liver disease.AimsTo assess the feasibility, safety and cell kinetics of autologous bone marrow-derived mononuclear cells (BMMCs) infusion in cirrhotic patients.MethodsBMMCs were isolated from autologous bone marrow and 10% of the cells were labelled with 99mTc-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.ResultsEight patients received 2.0-15.0 x 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).ConclusionsBMMCs 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.
AB - BackgroundBone marrow-derived cell therapy has been investigated in patients with severe liver disease.AimsTo assess the feasibility, safety and cell kinetics of autologous bone marrow-derived mononuclear cells (BMMCs) infusion in cirrhotic patients.MethodsBMMCs were isolated from autologous bone marrow and 10% of the cells were labelled with 99mTc-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.ResultsEight patients received 2.0-15.0 x 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).ConclusionsBMMCs 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.
UR - https://www.scopus.com/pages/publications/79551564823
U2 - 10.1111/j.1478-3231.2010.02424.x
DO - 10.1111/j.1478-3231.2010.02424.x
M3 - Article
SN - 1478-3223
VL - 31
SP - 391
EP - 400
JO - Liver International
JF - Liver International
IS - 3
ER -