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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 regeneration rate after 90% partial hepatectomy (a). Mitotic index of hepatocytes after 90% partial hepatectomy (b). Number of hepatocytes (c) and internuclear distance (d) at 72 hours after partial hepatectomy. (e) Histology of mitotic hepatocytes (arrows) 72 hours after 90% partial hepatectomy; liver slides were stained with H-E. 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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fig3: Liver regeneration rate after 90% partial hepatectomy (a). Mitotic index of hepatocytes after 90% partial hepatectomy (b). Number of hepatocytes (c) and internuclear distance (d) at 72 hours after partial hepatectomy. (e) Histology of mitotic hepatocytes (arrows) 72 hours after 90% partial hepatectomy; liver slides were stained with H-E. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD. Student's t-test, ∗P < .05, ∗∗P < .01.

Mentions: Interestingly, genes that promote liver regeneration were decreased in WBM group, whereas genes that halt hepatocyte division were increased. On the other hand, liver regeneration rate increased gradually after surgery, but without differences between groups at 6, 12, 24, or 48 hours. However, as shown in Figure 3(a), at 72 hours WBM group showed a lower regeneration rate compared to EC group (44% versus 59%, P = .003). Nevertheless, no differences were found in the number of mitotic cells in both groups (Figure 3(b)) and the number of hepatocytes at 72 hours after PH was also similar (Figure 3(c)). Surprisingly, the internuclear distance among hepatocytes was higher in EC group compared to WBM group at 72 hours (P = .003; Figure 3(d)), indicating that hepatocytes in WBM group were smaller than in EC group, resembling that of normal liver (data not shown). This could explain the lower regeneration rate, measured by changes in the remnant liver weight.


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 regeneration rate after 90% partial hepatectomy (a). Mitotic index of hepatocytes after 90% partial hepatectomy (b). Number of hepatocytes (c) and internuclear distance (d) at 72 hours after partial hepatectomy. (e) Histology of mitotic hepatocytes (arrows) 72 hours after 90% partial hepatectomy; liver slides were stained with H-E. 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

fig3: Liver regeneration rate after 90% partial hepatectomy (a). Mitotic index of hepatocytes after 90% partial hepatectomy (b). Number of hepatocytes (c) and internuclear distance (d) at 72 hours after partial hepatectomy. (e) Histology of mitotic hepatocytes (arrows) 72 hours after 90% partial hepatectomy; liver slides were stained with H-E. WBM: whole bone marrow; EC: empty capsules. Values are expressed as means ± SD. Student's t-test, ∗P < .05, ∗∗P < .01.
Mentions: Interestingly, genes that promote liver regeneration were decreased in WBM group, whereas genes that halt hepatocyte division were increased. On the other hand, liver regeneration rate increased gradually after surgery, but without differences between groups at 6, 12, 24, or 48 hours. However, as shown in Figure 3(a), at 72 hours WBM group showed a lower regeneration rate compared to EC group (44% versus 59%, P = .003). Nevertheless, no differences were found in the number of mitotic cells in both groups (Figure 3(b)) and the number of hepatocytes at 72 hours after PH was also similar (Figure 3(c)). Surprisingly, the internuclear distance among hepatocytes was higher in EC group compared to WBM group at 72 hours (P = .003; Figure 3(d)), indicating that hepatocytes in WBM group were smaller than in EC group, resembling that of normal liver (data not shown). This could explain the lower regeneration rate, measured by changes in the remnant liver weight.

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