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. 2017:2017:5270527.
doi: 10.1155/2017/5270527. Epub 2017 Feb 23.

Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy

Carlos Oscar Kieling  1 , Carolina Uribe-Cruz  2 , Mónica Luján López  3 , Alessandro Bersch Osvaldt  4 , Themis Reverbel da Silveira  1 , Ursula Matte  5
Affiliations

Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy

Carlos Oscar Kieling et al. Stem Cells Int. 2017.

Abstract

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 of Il-6 and Il-10 in 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.

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Conflict of interest statement

The authors have no conflict of interests to declare.

Figures

Figure 1
Figure 1
Survival rate for 10 days after 90% partial hepatectomy (PH). BMMC increase survival rate in rats submitted to PH (∗P = 0.003, log rank test). EC: empty capsules, BMMC: encapsulated bone marrow mononuclear cells.
Figure 2
Figure 2
(a) Liver regeneration rate at 6, 12, 24, 48, and 72 hours after 90% partial hepatectomy (PH). (b) Mitotic index at 6, 12, 24, 48, and 72 hours after 90% PH. (c) BrdU immunohistochemistry, BMMC 48 hours after 90% partial hepatectomy (20x). (d) Positive hepatocytes for BrdU, EC, and BMMC 24: 12.72 ± 12.38 and 5.9 ± 5.3, respectively; EC and BMMC 48: 10.34 ± 5.03 and 9.46 ± 3.49, respectively. Values are expressed as means ± SD. Student's t-test. EC: empty capsules, BMMC: encapsulated bone marrow mononuclear cells.
Figure 3
Figure 3
BMMC modulate liver cytokines. Liver gene expression of Il-6 (a) and Il-10 (b) at 6, 12, and 24 hours after 90% partial hepatectomy (PH). Values are expressed as means ± SD in log scale. Student's t-test, ∗P < 0.05. EC: empty capsules, BMMC: encapsulated bone marrow mononuclear cells.
Figure 4
Figure 4
CD68+ cells in liver sections, EC, and BMMC 72 hours after 90% partial hepatectomy ((a) and (b), resp.). (c) CD68 + cell quantification at 6, 12, 24, 48, and 72 hours after 90% partial hepatectomy (PH). Values are expressed as means ± SD. Student's t-test, ∗P = 0.003. EC: empty capsules, BMMC: encapsulated bone marrow mononuclear cells. Horizontal bar indicates normal values.
Figure 5
Figure 5
BMMC enhance apoptosis. (a) Caspase 3 activity and (b) liver gene expression of Caspase 3 after 90% partial hepatectomy. Values are expressed as means ± SD. Student's t-test, ∗P < 0.05. EC: empty capsules, BMMC: encapsulated bone marrow mononuclear cells.
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