Long-term Production of Glycogen and Hepatic-Derived, Cell-Invasion-Promoting Chemokines by Ultrasound-Driven Hepatic-Differentiated Human Bone Marrow Mesenchymal Stem Cells
- 3 March 2020
- journal article
- research article
- Published by Radiation Research Society in Radiation Research
- Vol. 193 (4), 394-405
- https://doi.org/10.1667/rr15421.1
Abstract
The current treatment for liver failure is restricted to surgical liver transplantation, which is technically complicated, limited by the shortage of available organs and presents major risks to the patient. Bone marrow mesenchymal stem cells (BMSCs) represent promising sources of hepatocyte-like cells for cell transplantation treatment. However, a safe and efficient induction method for their differentiation remains to be defined. Here we further optimized an effective technique by combining high-dose treatment with hepatocyte growth factor (HGF) and ultrasound stimulation. The optimized ultrasound parameter (1.0 W/cm2 intensity, 1 MHz frequency, 20% duty cycle, 100 Hz pulse repetition frequency, 60-s irradiation duration, triple times in three days) combined with different HGF doses (10, 20 and 50 ng/ml) was used to treat BMSCs. The results showed that the specific hepatic markers, including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen, were increased in a dose-dependent manner. Their concentration was then further increased when ultrasound irradiation was administered (P < 0.05), as indicated by PCR, Western blot and immunofluorescence staining as well as a glycogen synthesis test. Furthermore, analysis of the hepatocyte-derived chemokines showed elevated stromal cell-derived factor 1alpha (SDF-1α) and C-X-C chemokine receptor type 4 (CXCR4) after HGF treatment. Again, concentrations of those chemokines were further increased by ultrasound radiation (P < 0.05). The observed increased effect was sustained for 21 days. To summarize, we further defined the optimal combination of HGF and ultrasound treatment to increase the differentiation and chemotaxis of BMSCs in a safe, sustained and efficient manner. These findings provide a new perspective for stem cell orientation in the field of tissue engineering.Keywords
This publication has 35 references indexed in Scilit:
- Ultrasound Targeted Microbubble Destruction Stimulates Cellular Endocytosis in Facilitation of Adeno-Associated Virus DeliveryInternational Journal of Molecular Sciences, 2013
- Promotion of Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells on Decellularized Cell-Deposited Extracellular MatrixBioMed Research International, 2013
- Bio-effects and safety of low-intensity, low-frequency ultrasonic exposureProgress in Biophysics and Molecular Biology, 2012
- Identification of a pivotal endocytosis motif in c-Met and selective modulation of HGF-dependent aggressiveness of cancer using the 16-mer endocytic peptideOncogene, 2012
- In Vitro Differentiation of Embryonic and Adult Stem Cells into Hepatocytes: State of the ArtThe International Journal of Cell Cloning, 2009
- Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cellsBMC Cell Biology, 2008
- Ultrasound–biophysics mechanismsProgress in Biophysics and Molecular Biology, 2007
- Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF inductionBiochemical and Biophysical Research Communications, 2004
- Hepatocyte Growth Factor Induces Differentiation of Adult Rat Bone Marrow Cells into a Hepatocyte Lineage in VitroBiochemical and Biophysical Research Communications, 2000
- Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1Nature, 1996