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Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis
Clinical and Molecular Hepatology ; : 141-149, 2015.
Artículo en Inglés | WPRIM | ID: wpr-128618
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 (alpha-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 alpha-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-beta1 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 alpha-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.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Células de la Médula Ósea / Diferenciación Celular / Inmunofenotipificación / Interleucina-6 / Interleucina-10 / Factor de Crecimiento de Hepatocito / Apoptosis / Técnicas de Cocultivo / Factor de Crecimiento Transformador beta1 / Células Estrelladas Hepáticas Límite: Humanos Idioma: Inglés Revista: Clinical and Molecular Hepatology Año: 2015 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Células de la Médula Ósea / Diferenciación Celular / Inmunofenotipificación / Interleucina-6 / Interleucina-10 / Factor de Crecimiento de Hepatocito / Apoptosis / Técnicas de Cocultivo / Factor de Crecimiento Transformador beta1 / Células Estrelladas Hepáticas Límite: Humanos Idioma: Inglés Revista: Clinical and Molecular Hepatology Año: 2015 Tipo del documento: Artículo