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Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy.

Uribe-Cruz C, Kieling CO, López ML, Osvaldt A, Ochs de Muñoz G, da Silveira TR, Giugliani R, Matte U - Stem Cells Int (2015)

Bottom Line: Results.Conclusions.In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

View Article: PubMed Central - PubMed

Affiliation: Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil ; Post-Graduation Program on Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

ABSTRACT
Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

No MeSH data available.


Related in: MedlinePlus

Liver gene expression after 90% partial hepatectomy (PH). Liver gene expression of Tnf-α (a), Nfκ-B (b), Il-6 (c), Tlr-4 (d), and Myd88 (e) 6 hours after 90% partial hepatectomy and Socs3 (f), Hgf (g), and Tgf-β (h) 12, 24, and 48 hours after 90% partial hepatectomy. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD in log scale. Student's t-test, ∗P < .05, ∗∗P < .01.
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fig2: Liver gene expression after 90% partial hepatectomy (PH). Liver gene expression of Tnf-α (a), Nfκ-B (b), Il-6 (c), Tlr-4 (d), and Myd88 (e) 6 hours after 90% partial hepatectomy and Socs3 (f), Hgf (g), and Tgf-β (h) 12, 24, and 48 hours after 90% partial hepatectomy. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD in log scale. Student's t-test, ∗P < .05, ∗∗P < .01.

Mentions: First we assessed the expression levels of genes related to the early phase of liver regeneration. The expression of Tnf-α (P = .01) and Nfκ-B (P = .01) was markedly decreased in WBM group at 6 hours after 90% PH (Figures 2(a) and 2(b)). As a result, the expression of Il-6 was also decreased (P = .04) in the WBM group compared to EC group (Figure 2(c)). Interestingly, LPS receptor (Tlr-4) and its mediator (Myd88) showed no differences in gene expression between groups 6 hours after 90% HP (Figures 2(d) and 2(e)).


Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy.

Uribe-Cruz C, Kieling CO, López ML, Osvaldt A, Ochs de Muñoz G, da Silveira TR, Giugliani R, Matte U - Stem Cells Int (2015)

Liver gene expression after 90% partial hepatectomy (PH). Liver gene expression of Tnf-α (a), Nfκ-B (b), Il-6 (c), Tlr-4 (d), and Myd88 (e) 6 hours after 90% partial hepatectomy and Socs3 (f), Hgf (g), and Tgf-β (h) 12, 24, and 48 hours after 90% partial hepatectomy. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD in log scale. Student's t-test, ∗P < .05, ∗∗P < .01.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663362&req=5

fig2: Liver gene expression after 90% partial hepatectomy (PH). Liver gene expression of Tnf-α (a), Nfκ-B (b), Il-6 (c), Tlr-4 (d), and Myd88 (e) 6 hours after 90% partial hepatectomy and Socs3 (f), Hgf (g), and Tgf-β (h) 12, 24, and 48 hours after 90% partial hepatectomy. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD in log scale. Student's t-test, ∗P < .05, ∗∗P < .01.
Mentions: First we assessed the expression levels of genes related to the early phase of liver regeneration. The expression of Tnf-α (P = .01) and Nfκ-B (P = .01) was markedly decreased in WBM group at 6 hours after 90% PH (Figures 2(a) and 2(b)). As a result, the expression of Il-6 was also decreased (P = .04) in the WBM group compared to EC group (Figure 2(c)). Interestingly, LPS receptor (Tlr-4) and its mediator (Myd88) showed no differences in gene expression between groups 6 hours after 90% HP (Figures 2(d) and 2(e)).

Bottom Line: Results.Conclusions.In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

View Article: PubMed Central - PubMed

Affiliation: Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil ; Post-Graduation Program on Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

ABSTRACT
Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

No MeSH data available.


Related in: MedlinePlus