INTRODUCTION: Mesenchymal stem cells (MSCs) transplantation has been suggested to be effective for the treatment of liver fibrosis, but the mechanisms of action are not clearly elucidated. We transplanted encapsulated human MSCs in a mouse model of liver fibrosis to determine the mechanisms of the protective effect.
METHODS: Bone marrow-derived MSCs were isolated from human femoral heads. MSCs were microencapsulated using a novel alginate-poly(ethylene-glycol)hybrid-hydrogel (0.4mm). In vitro, we analyzed viability, proliferation, cytokine secretion, and differentiation capacity of encapsulated MSCs. In vivo, we transplanted encapsulated MSCs, encapsulated human fibroblasts, and empty microspheres into mice with liver fibrosis induced by bile-duct-ligation. Collagen was quantified in the livers over time and mRNA levels of fibrosis-related genes were quantified using RT-PCR.
RESULTS: The viability, proliferation and cytokine secretion of encapsulated MSCs was similar to non-encapsulated MSCs. Once exposed to specific medium, MSCs maintained their capacity to differentiate into adipocytes, chondrocyte, and osteocyte within the microspheres. When transplanted i.p. in mice with bile-duct-ligation, encapsulated MSCs delayed significantly the development of liver fibrosis, when compared to encapsulated fibroblasts or empty microspheres. Liver mRNA levels of alpha-smooth muscle actin and matrix metalloproteinase 13 were significantly lower, whereas matrix metalloproteinase 9 was significantly higher in mice treated with encapsulated MSCs.
CONCLUSION: Transplantation of encapsulated MSCs represents a promising strategy for local and systemic delivery of anti-inflammatory and immunomodulatory molecules secreted by MSCs.
To cite this abstract in AMA style:Meier R, Mahou R, Morel P, Muller Y, Christofilopoulos P, Wandrey C, Gonelle-Gispert C, Buhler L. Encapsulated Human Mesenchymal Stem Cells Reduce Alpha-Smooth Muscle Actin and Increase Matrix Metalloproteinase-9 Expression during Liver Fibrosis [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/encapsulated-human-mesenchymal-stem-cells-reduce-alpha-smooth-muscle-actin-and-increase-matrix-metalloproteinase-9-expression-during-liver-fibrosis/. Accessed October 27, 2020.
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