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Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells
Published on: March 5, 2019
Differentiation profile of peripheral blood-derived vascular progenitor cell predicts intimal hyperplasia after
Chao-Hung Wang1, I-Chang Hsieh, Wen-Jin Cherng
1Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taiwan. bearty@adm.cgmh.org.tw
Insights
Vascular progenitor cell (VPC) differentiation profiles predict intimal hyperplasia (IH) after stenting. Specific VPC phenotypes independently predict IH severity, aiding risk stratification for post-stent restenosis.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Medical Device Technology
Background:
- In-stent restenosis (ISR) is a significant complication following bare-metal stenting, primarily driven by intimal hyperplasia (IH).
- The number of circulating vascular progenitor cells (VPCs) post-stenting correlates with IH development.
- Predictive markers for IH remain crucial for patient management.
Purpose of the Study:
- To investigate whether the differentiation profile of VPCs can predict the development and severity of IH after bare-metal stenting.
- To identify specific VPC phenotypes associated with IH.
- To assess the additive value of VPC differentiation profiles to traditional risk factors for predicting IH.
Main Methods:
- Peripheral blood was collected from 58 patients post-stenting for VPC culture.
- VPC differentiation into endothelial (VE-cadherin positive) and smooth muscle (α-smooth muscle actin positive) lineages was assessed via flow cytometry.
- Intravascular ultrasound quantified IH area 6 months post-stenting.
Main Results:
- VPCs differentiated into four distinct phenotypes: α-SMA(-)VE-Cad(+), α-SMA(+)VE-cad(high), α-SMA(+)VE-cad(low), and α-SMA(+)VE-Cad(-).
- IH was significantly correlated with gender, smoking status, reference vessel diameter, minimal lumen diameter, stent area, and VPC differentiation parameters.
- Multivariate analysis identified the number of α-SMA(+)VE-Cad (low/-) VPCs and the ratio of α-SMA(+)VE-Cad (low/-) to α-SMA(-)VE-Cad(+) VPCs as independent predictors of IH, even after controlling for stent area, smoking, and gender.
Conclusions:
- The differentiation profile of VPCs independently predicts the severity of post-stent IH.
- Specific VPC phenotypes, particularly α-SMA(+)VE-Cad (low/-) cells, are strongly associated with IH development.
- VPC differentiation profiling offers a potential future tool for identifying patients at high risk of post-stent restenosis.
Abstract:
In-stent restenosis is largely due to intimal hyperplasia (IH). The number of vascular progenitor cells (VPCs) mobilized at the acute phase after stenting is associated with IH. This study sought to determine whether the differentiation profile of VPC predicts the development of IH. Peripheral blood was collected in 58 patients after bare-metal stenting to culture VPCs. Intravascular ultrasound was performed to estimate the area of IH 6 months after stenting. VPC differentiation was determined using flow cytometry. VE-cadherin (VE-Cad) and α-smooth muscle actin (α-SMA) were used to identify endothelial and smooth muscle cell lineages, respectively. After culturing, VPCs differentiated into four different phenotypes (α-SMA(-)VE-Cad(+), α-SMA(+)VE-cad(high), α-SMA(+)VE-cad(low), and α-SMA(+)VE-Cad(-)). IH was correlated with gender (P = 0.04), smoking status (P = 0.04), reference diameter (P = 0.03), minimal lumen diameter (P = 0.03), stent area (P < 0.0001), and parameters in the VPC differentiation profile (P < 0.05). Multivariate analysis controlling for stent area, smoking status, and gender revealed that IH was positively and independently associated with the number of differentiated α-SMA(+)VE-Cad (low/-) VPCs (P < 0.0001), and the ratio of α-SMA(+)VE-Cad (low/-) VPCs to α-SMA(-)VE-Cad(+) VPCs (P = 0.001). These parameters in the VPC differentiation profile independently predicted the IH and provided additive information to traditional risk factors. In conclusion, the profile of VPC differentiation predicts the severity of post-stent IH and may be a potential tool in the future for clinicians to identify patients at risk of post-stent restenosis.
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