Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells

Autor: Barbara Rinaldi, Marisa De Feo, Pasquale Santè, Umberto Galderisi, Amalia Forte, Liberato Berrino, Marilena Cipollaro, Loredana Sodano, Mario Grossi, Chiara Botti, Mauro Finicelli, Francesco Rossi, Gilda Cobellis
Přispěvatelé: Forte, A, Rinaldi, Barbara, Sodano, L, Berrino, Liberato, Rossi, Francesco, Finicelli, M, Grossi, M, Cobellis, Gilda, Botti, C, DE FEO, Marisa, Sante', Pasquale, Galderisi, Umberto, Cipollaro, Marilena
Rok vydání: 2011
Předmět:
Male
Vascular Endothelial Growth Factor A
Pathology
medicine.medical_treatment
Apoptosis
chemistry.chemical_compound
Restenosis
Carotid Stenosis
Pharmacology (medical)
Cells
Cultured
Mesenchymal stromal cell
Cell Cycle
Cell Differentiation
General Medicine
Stem-cell therapy
Vascular endothelial growth factor
Carotid Arteries
medicine.anatomical_structure
8-Hydroxy-2'-Deoxyguanosine
Cardiology
Cytokines
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Restenosi
Bone Marrow Cells
Arteriotomy
Mesenchymal Stem Cell Transplantation
Revascularization
Internal medicine
medicine
Animals
RNA
Messenger
Rats
Wistar
Cell Proliferation
Inflammation
Pharmacology
business.industry
Mesenchymal stem cell
Deoxyguanosine
Mesenchymal Stem Cells
medicine.disease
Toll-Like Receptor 2
Rats
Toll-Like Receptor 4
Stenosis
chemistry
Bone marrow
Carotid Artery Injuries
business
DNA Damage
Zdroj: Cardiovascular Drugs and Therapy. 26:9-21
ISSN: 1573-7241
0920-3206
DOI: 10.1007/s10557-011-6359-8
Popis: Purpose: 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. Methods: 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). Results: 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. Conclusions: 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.
Databáze: OpenAIRE
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