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Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis.

Jang YO, Jun BG, Baik SK, Kim MY, Kwon SO - Clin Mol Hepatol (2015)

Bottom Line: Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease.These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. ; Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea.

ABSTRACT

Background/aims: Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs.

Methods: We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs.

Results: The BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.

Conclusions: These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.

No MeSH data available.


Related in: MedlinePlus

Inhibition of viability and induction of apoptosis in activated HSCs by BM-MSCs. (A) The HSCs viability was decreased and (B) apoptosis was increased with direct co-culture system of activated HSCs with BM-MSCs. Values are presented as mean ± SD. *P<0.01. HSCs, hepatic stellate cells; MSCs, mesenchymal stem cells; BM-MSCs, bone marrow-derived mesenchymal stem cells.
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Figure 4: Inhibition of viability and induction of apoptosis in activated HSCs by BM-MSCs. (A) The HSCs viability was decreased and (B) apoptosis was increased with direct co-culture system of activated HSCs with BM-MSCs. Values are presented as mean ± SD. *P<0.01. HSCs, hepatic stellate cells; MSCs, mesenchymal stem cells; BM-MSCs, bone marrow-derived mesenchymal stem cells.

Mentions: At a 1:1 co-culture ratio, to determine whether BM-MSCs have the capacity to inhibit activated HSCs viability, we quantified the CellTiter 96® AQueous One Solution Reagent ELISA kit. And to determine whether BM-MSCs also have the capacity to reduce activated HSCs numbers by inducing their apoptosis, we quantified the Cell Death Detection ELISA kit. HSCs viability was decreased by 34% and apoptosis was increased by 3.7-fold with direct co-culture system of activated HSCs with BM-MSCs, respectively (P<0.01). We confirmed that BM-MSCs induced apoptosis of HSCs and also significantly inhibited viability of HSCs (Fig. 4).


Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis.

Jang YO, Jun BG, Baik SK, Kim MY, Kwon SO - Clin Mol Hepatol (2015)

Inhibition of viability and induction of apoptosis in activated HSCs by BM-MSCs. (A) The HSCs viability was decreased and (B) apoptosis was increased with direct co-culture system of activated HSCs with BM-MSCs. Values are presented as mean ± SD. *P<0.01. HSCs, hepatic stellate cells; MSCs, mesenchymal stem cells; BM-MSCs, bone marrow-derived mesenchymal stem cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493357&req=5

Figure 4: Inhibition of viability and induction of apoptosis in activated HSCs by BM-MSCs. (A) The HSCs viability was decreased and (B) apoptosis was increased with direct co-culture system of activated HSCs with BM-MSCs. Values are presented as mean ± SD. *P<0.01. HSCs, hepatic stellate cells; MSCs, mesenchymal stem cells; BM-MSCs, bone marrow-derived mesenchymal stem cells.
Mentions: At a 1:1 co-culture ratio, to determine whether BM-MSCs have the capacity to inhibit activated HSCs viability, we quantified the CellTiter 96® AQueous One Solution Reagent ELISA kit. And to determine whether BM-MSCs also have the capacity to reduce activated HSCs numbers by inducing their apoptosis, we quantified the Cell Death Detection ELISA kit. HSCs viability was decreased by 34% and apoptosis was increased by 3.7-fold with direct co-culture system of activated HSCs with BM-MSCs, respectively (P<0.01). We confirmed that BM-MSCs induced apoptosis of HSCs and also significantly inhibited viability of HSCs (Fig. 4).

Bottom Line: Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease.These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. ; Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea.

ABSTRACT

Background/aims: Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs.

Methods: We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs.

Results: The BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.

Conclusions: These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.

No MeSH data available.


Related in: MedlinePlus