Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy.
Acute liver failure is a complex and fatal disease. Cell-based therapies are a promising alternative therapeutic approach for liver failure due to relatively simple technique and lower cost. The use of semipermeable microcapsules has become an interesting tool for evaluating paracrine effects in vivo. In this study, we aimed to assess the paracrine effects of bone marrow mononuclear cells (BMMC) encapsulated in sodium alginate to treat acute liver failure in an animal model of 90% partial hepatectomy (90% PH). Encapsulated BMMC were able to increase 10-day survival without enhancing liver regeneration markers. Gene expression ofIl-6andIl-10in the remnant liver was markedly reduced at 6 h after 90% PH in animals receiving encapsulated BMMC compared to controls. This difference, however, was neither reflected by changes in the number of CD68+ cells nor by serum levels of IL6. On the other hand, treated animals presented increased caspase activity and gene expression in the liver. Taken together, these results suggest that BMMC regulate immune response and promote apoptosis in the liver after 90% PH by paracrine factors. These changes ultimately may be related to the higher survival observed in treated animals, suggesting that BMMC may be a promising alternative to treat acute liver failure.
Experimental Laboratory of Gastroenterology and Hepatology, HCPA, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil; Post-Graduation Program on Medicine: Sciences in Gastroenterology, UFRGS, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil.
Carlos Oscar
CO
Kieling
Experimental Laboratory of Gastroenterology and Hepatology, HCPA, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil; Post-Graduation Program on Medicine: Sciences in Gastroenterology, UFRGS, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil; Gene Therapy Center, HCPA, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil.
Carolina
C
Uribe-Cruz
Gene Therapy Center, HCPA, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil; Post-Graduation Program on Genetics and Molecular Biology, UFRGS, Av. Bento Gonçalves 9500, 91501-970 Porto Alegre, RS, Brazil.
Mónica Luján
ML
López
Post-Graduation Program in Surgery, UFRGS, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil.
Alessandro Bersch
AB
Osvaldt
Experimental Laboratory of Gastroenterology and Hepatology, HCPA, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil; Post-Graduation Program on Medicine: Sciences in Gastroenterology, UFRGS, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil.
Themis Reverbel
TR
da Silveira
Gene Therapy Center, HCPA, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil; Post-Graduation Program on Genetics and Molecular Biology, UFRGS, Av. Bento Gonçalves 9500, 91501-970 Porto Alegre, RS, Brazil; Post-Graduation Program in Child and Adolescent Health, UFRGS, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil.
Ursula
0000-0003-4977-6662
U
Matte