Strategies to enhance the efficiency of endothelial progenitor cell therapy by ephrin B2 pretreatment and coadministration with smooth muscle progenitor cells on vascular function during the wound-healing process in irradiated or nonirradiated condition
| Autor: | Jean-Sébastien Silvestre, Claire Squiban, Valerie Holler, Radia Tamarat, Marc Benderitter, Carole Dean, Philippe Foubert, Valérie Buard, Bernard I. Levy, Gérard Tobelem |
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| Přispěvatelé: | PRP-HOM/SRBE/LRTE, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de recherche en régénération des tissus sains irradiés [Fontenay-aux-Roses] (LR2I), Institut de Radioprotection et de Sûreté Nucléaire - IRSN [Fontenay-aux-Roses], PRP-HOM/SRBE/LRTOX, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
[SDV]Life Sciences [q-bio] Myocytes Smooth Muscle Biomedical Engineering lcsh:Medicine Vascular permeability Stimulation Ephrin-B2 Pharmacology Biology Endothelial progenitor cell Neovascularization Cell therapy 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Humans Progenitor cell 030304 developmental biology Aged Endothelial Progenitor Cells 0303 health sciences Transplantation Wound Healing lcsh:R Cell Biology Middle Aged Immunohistochemistry 030220 oncology & carcinogenesis Immunology embryonic structures cardiovascular system Female medicine.symptom Wound healing circulatory and respiratory physiology |
| Zdroj: | Cell Transplantation Cell Transplantation, 2015, 24 (7), pp.1343-1361. ⟨10.3727/096368913X672064⟩ Cell Transplantation, Vol 24 (2015) |
| ISSN: | 0963-6897 |
| DOI: | 10.3727/096368913X672064⟩ |
| Popis: | International audience; Endothelial progenitor cell (EPC) transplantation has beneficial effects for therapeutic neovascularization. We therefore assessed the effect of a therapeutic strategy based on EPC administration in the healing of radiation-induced damage. To improve cell therapy for clinical use, we used pretreatment with ephrin B2-Fc (Eph-B2-Fc) and/or coadministration with smooth muscle progenitor cells. At day 3, EPCs promoted dermal wound healing in both nonirradiated and irradiated mice by 1.2- and 1.15-fold, respectively, compared with animals injected with phosphate-buffered saline. In addition, EPCs also improved skin-blood perfusion and capillary density in both irradiated and nonirradiated mice compared with PBS-injected animals. We also demonstrated that activation with Eph-B2-Fc increased wound closure by 1.6-fold compared with unstimulated EPCs in nonirradiated mice. Interestingly, the beneficial effect of Eph-B2-Fc was abolished in irradiated animals. In addition, we found that Eph-B2-Fc stimulation did not improve EPC-induced vascular permeability or adhesiveness compared to unstimulated EPCs. We hypothesized that this effect was due to high oxidative stress during irradiation, leading to inhibition of EPCs' beneficial effect on vascular function. In this line, we demonstrated that, in irradiated conditions, N-acetyl-L-cysteine treatment restored the beneficial effect of EPC stimulation with Eph-B2-Fc in the wound healing process. In conclusion, stimulation by Eph-B2-Fc improved the beneficial effect of EPCs in physiological conditions and irradiated conditions only in association with antioxidant treatment. Additionally, cotherapy was beneficial in pathological conditions. © 2015 Cognizant Comm. Corp. |
| Databáze: | OpenAIRE |
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