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Published on: March 4, 2016
Introduction of embryonic stem cells into vein grafts reduces intimal hyperplasia in mice
S Breuer1, P Fogelstrand, H Lindskog
1Department of Vascular and Endovascular Surgery, University Clinic of Cologne, Cologne, Germany - silke.breuer@uk-koeln.de.
Insights
Embryonic stem cells significantly reduced intimal hyperplasia in vein grafts. This finding offers a promising therapeutic approach for improving vascular graft patency and reducing cardiovascular events.
Area of Science:
- Regenerative Medicine
- Vascular Biology
- Stem Cell Therapy
Background:
- Atherosclerosis and its complications are leading causes of death globally.
- Vein grafts are preferred for peripheral arterial disease but suffer from intimal hyperplasia, limiting long-term patency.
- Current interventional treatments have limitations, necessitating improved graft strategies.
Purpose of the Study:
- To investigate the efficacy of embryonic stem cells in mitigating intimal hyperplasia within vein grafts.
- To evaluate the potential of stem cell therapy to enhance vascular graft performance in vivo.
Main Methods:
- Murine embryonic stem cells (LacZ-tagged) were implanted into decellularized vein grafts.
- Control groups included untreated veins, decellularized veins, and decellularized veins with other cell types or materials.
- Grafts were analyzed after six weeks for intimal thickening using immunohistochemistry and morphological assessment.
Main Results:
- Vein grafts with implanted embryonic stem cells exhibited significantly reduced intimal thickening compared to all control groups.
- Control groups demonstrated substantial intimal hyperplasia, indicating the detrimental progression of the condition without stem cell intervention.
- Quantitative analysis showed a marked decrease in intimal hyperplasia in stem cell-treated grafts.
Conclusions:
- Embryonic stem cells possess therapeutic potential to favorably modulate intimal hyperplasia.
- This study supports embryonic stem cell implantation as a viable strategy to improve vascular graft outcomes.
- The findings suggest a novel approach to combat intimal hyperplasia and enhance the durability of vascular bypasses.
Aim:
Atherosclerosis with its cardiovascular events including cardiac and peripheral ischemia represents the main cause of death in the developed countries. Although interventional treatments like percutaneous transluminal angioplasty or stents are increasingly applied for the treatment of peripheral arterial disease, they are not always technically applicable or durable and bypass surgery is needed. Compared to synthetic grafts, vein grafts show a better patency especially when used for the lower leg as well as a lower risk for infection compared to synthetic grafts. Still the long-term patency rates are unsatisfactory due to accelerated intimal hyperplasia, a thickening of the vessel wall. The aim of this study was to elucidate, if the implantation of embryonic stem cells into vein grafts can reduce the development of intimal hyperplasia in a mouse in vivo model.
Methods:
In this study we implanted LacZ-tagged (ROSA26) murine embryonic stem cells into decellularized vein grafts. Control groups were: 1) untreated veins; 2) decellularized veins; 3) decellularized veins with gel and plastic film; and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film. Six weeks after insertion into the carotid artery of mice, the grafts were excised and analyzed immunohistochemically, morphologically, and by x-gal staining and compared to the control groups. The Mann-Whitney U test was used to compare groups. Statistical significance was indicated by a value of P<0.05.
Results:
Decellularized veins with implanted stem cells showed significantly less intimal thickening compared to all control groups (intimal hyperplasia vs. luminal circumference mean±SD 7.3±3.5 µm, median 8 µm). The control groups: 1) untreated veins (60.3±25.5 µm, median 58.5 µm); 2) decellularized veins (53.9±22.4 µm, median 48.4 µm); 3) decellularized veins with gel and plastic film (70.6±22.4 µm, median 72.6 µm); and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film (73.5±18.1 µm, median 73.6 µm) all showed the same high degree of intimal hyperplasia.
Conclusion:
This study demonstrates that embryonic stem cells have a therapeutic competence to favourably modulate intimal hyperplasia in vivo.
