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Forearm ischemia decreases endothelial colony-forming cell angiogenic potential
Institution:1. Université Paris Descartes, Sorbonne Paris Cite, Paris, France;2. Inserm UMR_S765, Faculté de Pharmacie, Paris, France;3. AP-HP, Hôpital Européen Georges Pompidou, Service d''Hématologie Biologique, Paris, France;4. Inserm UMR_S1076, Université de la Méditerranée, Faculté de Pharmacie, Marseille, France;5. Inserm UMR_S970, PARCC, Paris, France;6. AP-HP, Hôpital Européen Georges Pompidou, Service de Pharmacologie Clinique, Paris, France;7. AP-HP, Hôpital Européen Georges Pompidou, Centre d''Investigations Cliniques 9201, Paris, France;1. Nagasaki Harbor Medical Center, Nagasaki, Japan;2. Tosei General Hospital, Seto, Japan;3. Kyoto Kujo Hospital, Kyoto, Japan;4. Yokohama City University Medical Center, Yokohama, Japan;5. Tokai University, Isehara, Japan;6. Fukuoka Heart Clinic, Fukuoka, Japan;7. Jichi Medical University, Utsunomiya, Japan;8. Shin-Koga Hospital, Kurume, Japan;9. Hyogo College of Medicine, Nishinomiya, Japan;10. Kumamoto Rosai Hospital, Yatsushiro, Japan;11. Krishna Institute of Medical Sciences, Hyderabad, India;12. Global Hospitals, Hyderabad, India;13. Kin-ikyo Central Hospital, Sapporo, Japan;14. Sakurakai Takahashi Hospital, Kobe, Japan;15. Saiseikai Narashino Hospital, Narashino, Japan;p. Shonan Atsugi Hospital, Atsugi, Japan;q. Sapporo Higashi Tokushukai Hospital, Sapporo, Japan;r. Cheng-Hsin General Hospital, Taipei, Taiwan;s. Aomori Prefectural Central Hospital, Aomori, Japan;t. Shonan Kamakura General Hospital, Kamakura, Japan;1. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy;2. Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy;3. Fondazione IRCCS, Neurological Institute Carlo Besta, Milan, Italy;1. Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;2. Physiology Research Centre, Kerman University of Medical Sciences, Kerman, Iran;3. Afzal Research Institute (NGO), Kerman, Iran;4. Department of Midwifery, Kerman University of Medical Sciences, Kerman, Iran;5. Department of Microbiology, Virology and Immunology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;6. Reproductive and Genetic Unit, Research and Clinical Centre for Infertility, Yazd University of Medical Sciences, Yazd, Iran;7. Neuroscience Research Centre, Kerman University of Medical Sciences, Kerman, Iran;1. Department of Plastic Surgery, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing, People''s Republic of China;2. Department of Burn and Plastic Surgery, Burns Institute, The First Affiliated Hospital of PLA General Hospital, Beijing, People''s Republic of China;3. Department of Plastic Surgery, PLA General Hospital, Beijing, People''s Republic of China;4. School of Electrical and Information Engineering, Wuhan Institute of Technology, Wuhan, People''s Republic of China
Abstract:Background aimsCirculating endothelial progenitor cells and especially endothelial colony-forming cells (ECFCs) are promising candidate cells for endothelial regenerative medicine of ischemic diseases, but the conditions for an optimal collection from adult blood must be improved.MethodsOn the basis of a recently reported vascular niche of ECFCs, we hypothesized that a local ischemia could trigger ECFC mobilization from the vascular wall into peripheral blood to optimize their collection for autologous implantation in critical leg ischemia. Because the target population with critical leg ischemia is composed of elderly patients in whom a vascular impairment has been documented, we also analyzed the impact of aging on ECFC mobilization and vascular integrity.ResultsAfter having defined optimized ECFC culture conditions, we studied the effect of forearm ischemia on ECFC numbers and functions in 26 healthy volunteers (13 volunteers ages 20–30-years old versus 13 volunteers ages 60–70 years old). The results show that forearm ischemia induced an efficient local ischemia and a normal endothelial response but did not mobilize ECFCs regardless of the age group. Moreover, we report an alteration of angiogenic properties of ECFCs obtained after forearm ischemia, in vitro as well as in vivo in a hindlimb ischemia murine model. This impaired ECFC angiogenic potential was not associated with a quantitative modification of the circulating endothelial compartment.ConclusionsThe procedure of local ischemia, although reulting in a preserved endothelial reactivity, did not mobilize ECFCs but altered their angiogenic potential.
Keywords:aging  endothelial colony-forming cells  endothelial progenitor cells  forearm ischemia  mobilization
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