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2017 ; 10
(1
): 69-75
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Bone Marrow Stem Cells Anti-liver Fibrosis Potency: Inhibition of Hepatic
Stellate Cells Activity and Extracellular Matrix Deposition
#MMPMID28531915
Sitanggang EJ
; Antarianto RD
; Jusman SWA
; Pawitan JA
; Jusuf AA
Int J Stem Cells
2017[May]; 10
(1
): 69-75
PMID28531915
show ga
Transplantation of bone marrow derived stem cells (BMSCs) has been reported
inhibits liver fibrosis. Several in vitro studies by co-culturing BMSCs and
hepatic stellate cells (HSCs) indirectly or directly in 2D models showed
inhibition of HSC as the key player in liver fibrosis. In this study, we
investigated direct effect of BMSCs on HSCs by co-culturing BMSCs and HSCs in 3D
model as it represents the liver microenvironment with intricate cell-cell and
cell-matrix interactions. Primary isolated rat HSCs and BMSCs were directly
co-cultured at 1:1 ratio with hanging drop method. The monoculture of rat HSCs
served as positive control. Mono-culture and co-culture samples were harvested on
day 3, 5 and 7 for histological analysis. The samples were analyzed for
extracellular matrix deposition by Masson's Trichrome staining, tenascin-C
immunocytochemistry, resting HSC's state as shown by positive Oil Red O stained
cells. Our results indicated CD90(?)CD34(-) BMSCs anti-liver fibrosis potency as
evidenced by higher proportion of Oil Red O-positive cells in the co-culture
group compared to the monoculture group and the significant decrease in
extracellular matrix deposition as well as the decrease in tenascin-C expression
in the co-culture group (p<0.05) compared to the monoculture group. These
findings demonstrate that BMSCs have a potential therapeutic effect against liver
fibrotic process through their capacity to inhibit HSCs activation and their
effect in minimizing extracellular matrix deposition.