Journal article
Microencapsulated human mesenchymal stem cells decrease liver fibrosis in mice.
- Meier RP Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland. Electronic address: Raphael.meier@hcuge.ch.
- Mahou R Institut d'Ingénierie Biologique et Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Morel P Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
- Meyer J Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
- Montanari E Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
- Muller YD Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
- Christofilopoulos P Orthopedic Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
- Wandrey C Institut d'Ingénierie Biologique et Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Gonelle-Gispert C Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
- Bühler LH Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.
- 2014-12-03
Published in:
- Journal of hepatology. - 2015
Alginate
Cell transplantation
Inflammation
Interleukin 1 receptor antagonist
Liver fibrosis
Mesenchymal stem cells
Mice
Microencapsulation
Adult
Adult Stem Cells
Alanine Transaminase
Alginates
Animals
Aspartate Aminotransferases
Bile Ducts
Carbon Tetrachloride
Cell Proliferation
Cell Survival
Culture Media, Conditioned
Cytokines
Hepatic Stellate Cells
Heterografts
Humans
Ligation
Liver Cirrhosis, Experimental
Male
Matrix Metalloproteinase 9
Mesenchymal Stem Cell Transplantation
Mice
Mice, Inbred DBA
Microspheres
Polyethylene Glycols
RNA, Messenger
English
BACKGROUND & AIMS
Mesenchymal stem cell (MSC) transplantation was shown to be effective for the treatment of liver fibrosis, but the mechanisms of action are not yet fully understood. We transplanted encapsulated human MSCs in two mouse models of liver fibrosis to determine the mechanisms behind the protective effect.
METHODS
Human bone marrow-derived MSCs were microencapsulated in novel alginate-polyethylene glycol microspheres. In vitro, we analyzed the effect of MSC-conditioned medium on the activation of hepatic stellate cells and the viability, proliferation, cytokine secretion, and differentiation capacity of encapsulated MSCs. The level of fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride (CCl4) was assessed after intraperitoneal transplantation of encapsulated MSCs, encapsulated human fibroblasts, and empty microspheres.
RESULTS
MSC-conditioned medium inhibited hepatic stellate cell activation and release of MSC secreted anti-apoptotic (IL-6, IGFBP-2) and anti-inflammatory (IL-1Ra) cytokines. Viability, proliferation, and cytokine secretion of microencapsulated MSCs were similar to those of non-encapsulated MSCs. Within the microspheres, MSCs maintained their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. 23% (5/22) of the MSC clones were able to produce anti-inflammatory IL-1Ra in vitro. Microencapsulated MSCs significantly delayed the development of BDL- and CCl4-induced liver fibrosis. Fibroblasts had an intermediate effect against CCl4-induced fibrosis. Mice transplanted with encapsulated MSCs showed lower mRNA levels of collagen type I, whereas levels of matrix metalloproteinase 9 were significantly higher. Human IL-1Ra was detected in the serum of 36% (4/11) of the mice transplanted with microencapsulated MSCs.
CONCLUSIONS
MSC-derived soluble molecules are responsible for an anti-fibrotic effect in experimental liver fibrosis.
Mesenchymal stem cell (MSC) transplantation was shown to be effective for the treatment of liver fibrosis, but the mechanisms of action are not yet fully understood. We transplanted encapsulated human MSCs in two mouse models of liver fibrosis to determine the mechanisms behind the protective effect.
METHODS
Human bone marrow-derived MSCs were microencapsulated in novel alginate-polyethylene glycol microspheres. In vitro, we analyzed the effect of MSC-conditioned medium on the activation of hepatic stellate cells and the viability, proliferation, cytokine secretion, and differentiation capacity of encapsulated MSCs. The level of fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride (CCl4) was assessed after intraperitoneal transplantation of encapsulated MSCs, encapsulated human fibroblasts, and empty microspheres.
RESULTS
MSC-conditioned medium inhibited hepatic stellate cell activation and release of MSC secreted anti-apoptotic (IL-6, IGFBP-2) and anti-inflammatory (IL-1Ra) cytokines. Viability, proliferation, and cytokine secretion of microencapsulated MSCs were similar to those of non-encapsulated MSCs. Within the microspheres, MSCs maintained their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. 23% (5/22) of the MSC clones were able to produce anti-inflammatory IL-1Ra in vitro. Microencapsulated MSCs significantly delayed the development of BDL- and CCl4-induced liver fibrosis. Fibroblasts had an intermediate effect against CCl4-induced fibrosis. Mice transplanted with encapsulated MSCs showed lower mRNA levels of collagen type I, whereas levels of matrix metalloproteinase 9 were significantly higher. Human IL-1Ra was detected in the serum of 36% (4/11) of the mice transplanted with microencapsulated MSCs.
CONCLUSIONS
MSC-derived soluble molecules are responsible for an anti-fibrotic effect in experimental liver fibrosis.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1016/j.jhep.2014.10.030
- PMID 25450712
- Persistent URL
- https://folia.unifr.ch/global/documents/174618
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