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Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading
Haiying Huang1, Yasuhide Nakayama, Kairong Qin
1Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
Summary
Mechanical stress in vitro can guide embryonic stem cells to differentiate into vascular wall cells. This study shows physical forces promote cell alignment and differentiation, paving the way for engineered vascular tissues.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Vascular Tissue Engineering
Background:
- Embryonic stem cells (ES cells) hold potential for regenerative medicine.
- Generating vascular wall cells from ES cells is crucial for tissue engineering.
- Physical stimuli are increasingly recognized for their role in cell differentiation.
Purpose of the Study:
- To investigate the differentiation of murine ES cells into vascular wall cells using mechanical stress.
- To explore the effect of pulsatile flow and strain on ES cell differentiation and organization in vitro.
- To assess the potential for creating hierarchically structured vascular grafts using physically synchronized ES cell differentiation.
Main Methods:
- Murine ES cells, including Flk1-positive cells, were cultured on a compliant microporous polyurethane tube.
- Cells were exposed to static conditions or pulsatile flow simulating venous systems (wall shear stress and circumferential strain).
- Vascular endothelial growth factor (VEGF) was used during initial preincubation but omitted during mechanical stimulation.
Main Results:
- Static conditions led to random, smooth muscle actin (SMA)-positive cell layers.
- Pulsatile flow induced regular orientation of superficial cells, positive for platelet endothelial cell adhesion molecule 1 (PECAM1), resembling endothelial cells.
- Deeper cells showed smooth muscle-like characteristics (SMA-positive), suggesting simultaneous differentiation and segregation into distinct cell types.
- The combination of wall shear stress (WSS) and circumferential strain (CS) appeared to encourage differentiation and segregation.
Conclusions:
- Physical forces, specifically WSS and CS, can synchronize the differentiation of ES cells into distinct vascular cell types (endothelial-like and smooth muscle-like).
- This physical synchronization enables cell segregation, potentially allowing for the construction of hierarchically structured hybrid vascular prostheses.
- In vitro mechanical stimulation offers a promising strategy for engineering complex vascular tissues from stem cells.