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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

Mechanisms of cell death after 90% partial hepatectomy (PH). (a) Liver gene expression of Caspase 3 at 6, 12, 24, 48, and 72 hours after 90% PH. (b) Caspase 3 activity and (c) lysosomal-β-glucuronidase (Gusb) activity at 24, 48, and 72 hours after 90% PH. Gray bar indicates normal values. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD. Student's t-test, ∗P < .05; ∗∗P < .01.
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fig4: Mechanisms of cell death after 90% partial hepatectomy (PH). (a) Liver gene expression of Caspase 3 at 6, 12, 24, 48, and 72 hours after 90% PH. (b) Caspase 3 activity and (c) lysosomal-β-glucuronidase (Gusb) activity at 24, 48, and 72 hours after 90% PH. Gray bar indicates normal values. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD. Student's t-test, ∗P < .05; ∗∗P < .01.

Mentions: Since no differences were found regarding cell proliferation, we then investigated if encapsulated WBM cells could lead to differential cell death. In order to assess possible mechanisms of cell death associated with our results, we quantified Caspase 3 as a measure of apoptosis and Gusb activity as an indicator of necrosis. We observed that WBM group had higher levels of Casp3 at all times points (P < .05, Figure 4(a)), except at 72 hours where there was no difference between groups. Caspase 3 activity was also assessed in liver homogenates at 24, 48, and 72 hours. It was increased in WBM compared to EC group only at 48 hours (P = .013; Figure 4(b)), suggesting that cells from WBM group are dying by apoptosis. Interestingly when we evaluated Gusb activity at the same time point, WBM group presented less activity at 72 hours than EC group (P = .009; Figure 4(c)) suggesting that hepatocytes from EC group are dying by necrosis.


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)

Mechanisms of cell death after 90% partial hepatectomy (PH). (a) Liver gene expression of Caspase 3 at 6, 12, 24, 48, and 72 hours after 90% PH. (b) Caspase 3 activity and (c) lysosomal-β-glucuronidase (Gusb) activity at 24, 48, and 72 hours after 90% PH. Gray bar indicates normal values. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD. 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

fig4: Mechanisms of cell death after 90% partial hepatectomy (PH). (a) Liver gene expression of Caspase 3 at 6, 12, 24, 48, and 72 hours after 90% PH. (b) Caspase 3 activity and (c) lysosomal-β-glucuronidase (Gusb) activity at 24, 48, and 72 hours after 90% PH. Gray bar indicates normal values. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD. Student's t-test, ∗P < .05; ∗∗P < .01.
Mentions: Since no differences were found regarding cell proliferation, we then investigated if encapsulated WBM cells could lead to differential cell death. In order to assess possible mechanisms of cell death associated with our results, we quantified Caspase 3 as a measure of apoptosis and Gusb activity as an indicator of necrosis. We observed that WBM group had higher levels of Casp3 at all times points (P < .05, Figure 4(a)), except at 72 hours where there was no difference between groups. Caspase 3 activity was also assessed in liver homogenates at 24, 48, and 72 hours. It was increased in WBM compared to EC group only at 48 hours (P = .013; Figure 4(b)), suggesting that cells from WBM group are dying by apoptosis. Interestingly when we evaluated Gusb activity at the same time point, WBM group presented less activity at 72 hours than EC group (P = .009; Figure 4(c)) suggesting that hepatocytes from EC group are dying by necrosis.

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