Pretreating mesenchymal stem cells with electrical stimulation causes sustained long-lasting pro-osteogenic effects

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Cell Biology

Background:

• Electrical stimulation (ES) is clinically used for bone fractures and shows promise for bone tissue engineering (BTE).
• ES positively influences stem cell behaviors crucial for BTE, including migration, proliferation, and differentiation.
• Previous studies demonstrated ES accelerates Mesenchymal Stem Cell (MSC) osteogenic differentiation.

Purpose of the Study:

• To determine the optimal electrical stimulation (ES) regimen for maximizing pro-osteogenic effects in Mesenchymal Stem Cells (MSCs).
• To investigate the duration of ES needed to enhance osteogenic differentiation in MSCs.
• To assess the sustained effects of ES on osteogenic differentiation after treatment discontinuation.

Main Methods:

• Rat bone marrow-derived MSCs were exposed to 100 mV/mm ES for 1 hour daily over three, seven, and 14 days.
• Osteogenic differentiation was assessed at Day 14 by measuring collagen, calcium deposition, alkaline phosphatase, and osteogenic gene expression.
• Sustained effects were evaluated by culturing cells for seven days post-ES treatment.

Main Results:

• Three days of ES showed minimal effect on osteogenic differentiation.
• Seven and 14 days of ES significantly increased collagen and calcium deposition.
• Seven and 14 days of ES significantly upregulated osteogenic marker genes (Col1a1, Osteopontin, Osterix, Calmodulin).
• A seven-day ES regimen maintained pro-osteogenic activity for at least seven days post-treatment.

Conclusions:

• Seven and 14 days of ES significantly enhance MSC osteogenic differentiation, unlike three days.
• A seven-day ES regimen provides a sustained pro-osteogenic effect, potentially due to increased RunX2 and Calmodulin expression.
• Incorporating this sustained ES effect into BTE protocols could improve therapeutic outcomes.