Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells
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Restenosis is a complex and heterogeneous pathophysiological phenomenon occurring in patients submitted to revascularization procedures. Previous studies proved the antirestenotic properties of injected allogenic mesenchymal stromal cells (MSCs) in an experimental model of rat carotid (re)stenosis induced through arteriotomy. In this study we describe some of the effects subsequent to MSC treatment of rats submitted to carotid arteriotomy and possibly responsible for their antirestenotic effect.
Rat MSCs were isolated from bone marrow, expanded in vitro and characterized. Subsequently, we evaluated the effects of MSC administration via tail vein at 3 and 7 days after carotid arteriotomy both in rat serum and in injured carotids, focusing on DNA oxidative damage (8-oxo-dG detection), cell proliferation index (BrdU incorporation assay), apoptotic index (TUNEL assay), the expression of inflammation- and proliferation-related genes (RT-PCR), the release of growth factors and of inflammation-related cytokines (antibody arrays and ELISA).
MSC administration induced a greater cell proliferation in carotids after arteriotomy, together with an increased level of VEGF in the serum and with the higher expression of VEGF mRNA in injured carotids. Serum analysis also revealed a decreased level of the pro-inflammatory cytokines CXCL1, CXCL5, L-Selectin, ICAM-1 and LIX, and of TIMP1 and SDF-1alpha in MSC-treated rats. The MSC immunomodulatory activity was confirmed by the decreased expression of TLR2 and TLR4 in injured carotids.
MSCs play an immunomodulatory paracrine role when injected in rats submitted to carotid arteriotomy, accompanied by the release of VEGF, possibly contributing to the accelerated repair of the injured vascular wall.
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- Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells
Cardiovascular Drugs and Therapy
Volume 26, Issue 1 , pp 9-21
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Mesenchymal stromal cells
- Vascular endothelial growth factor
- Industry Sectors
- Amalia Forte (1) (5)
- Barbara Rinaldi (1) (5)
- Loredana Sodano (1) (5)
- Liberato Berrino (1) (5)
- Francesco Rossi (1) (5)
- Mauro Finicelli (4)
- Mario Grossi (1) (5)
- Gilda Cobellis (3) (5)
- Chiara Botti (3) (5)
- Marisa De Feo (2) (5)
- Pasquale Santè (2) (5)
- Umberto Galderisi (1) (5)
- Marilena Cipollaro (1) (5)
- Author Affiliations
- 1. Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio, 7-80138, Naples, Italy
- 5. Excellence Research Center for Cardiovascular Diseases, Second University of Naples, Naples, Italy
- 4. Human Health Foundation, Terni, Italy
- 3. Department of General Pathology, Second University of Naples, Via L. De Crecchio, 7-80138, Naples, Italy
- 2. Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Via L. De Crecchio, 7-80138, Naples, Italy