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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

Cytokine levels of TGF-β1, HGF, IL-6, and IL-10. Indirect co-culture system of activated HSCs with BM-MSCs decreased the production of (A) TGF-β1 and (B) IL-6. Whereas, co-culture system of activated HSCs with BM-MSCs increased the production of (C) HGF and (D) IL-10. 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 3: Cytokine levels of TGF-β1, HGF, IL-6, and IL-10. Indirect co-culture system of activated HSCs with BM-MSCs decreased the production of (A) TGF-β1 and (B) IL-6. Whereas, co-culture system of activated HSCs with BM-MSCs increased the production of (C) HGF and (D) IL-10. 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: To determine whether BM-MSC paracrine factors could modulate activated HSCs via indirect co-culture system. Measurement of TGF-β1, HGF, IL-6, and IL-10 from supernatant of co-cultured medium were done by ELISA. An indirect co-culture system of activated HSCs with BM-MSCs decreased the production of TGF-β1 by 75% and IL-6 by 16%, respectively (P<0.01, Fig. 3). Whereas, co-culture system of activated HSCs with BM-MSCs increased the production of HGF by 3.0-fold and IL-10 by 3.2-fold, respectively (P<0.01, Fig. 3).


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)

Cytokine levels of TGF-β1, HGF, IL-6, and IL-10. Indirect co-culture system of activated HSCs with BM-MSCs decreased the production of (A) TGF-β1 and (B) IL-6. Whereas, co-culture system of activated HSCs with BM-MSCs increased the production of (C) HGF and (D) IL-10. 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 3: Cytokine levels of TGF-β1, HGF, IL-6, and IL-10. Indirect co-culture system of activated HSCs with BM-MSCs decreased the production of (A) TGF-β1 and (B) IL-6. Whereas, co-culture system of activated HSCs with BM-MSCs increased the production of (C) HGF and (D) IL-10. 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: To determine whether BM-MSC paracrine factors could modulate activated HSCs via indirect co-culture system. Measurement of TGF-β1, HGF, IL-6, and IL-10 from supernatant of co-cultured medium were done by ELISA. An indirect co-culture system of activated HSCs with BM-MSCs decreased the production of TGF-β1 by 75% and IL-6 by 16%, respectively (P<0.01, Fig. 3). Whereas, co-culture system of activated HSCs with BM-MSCs increased the production of HGF by 3.0-fold and IL-10 by 3.2-fold, respectively (P<0.01, Fig. 3).

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