Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

Autor: Sara Eslava-Alcon, Mª Carmen Perez-Segura, Ana Serrano, Rafael Moreno-Luna, Almudena González-Rovira, Martin R. Larsen, Margarita Jimenez-Palomares, Mª Jesús Extremera-García, Marta Rojas-Torres, Manuel Rodriguez-Piñero, Jose Angel Alonso-Piñero, Borja Antequera-González, Ismael Sánchez-Gomar, Antonio Rosal-Vela, Mª Carmen Duran-Ruiz, Lucía Beltrán-Camacho
Přispěvatelé: Biomedicina, Biotecnología y Salud Pública, [Beltran-Camacho,L, Jimenez-Palomares,M, Rojas-Torres,M, Sanchez-Gomar,I, Rosal-Vela,A, Eslava-Alcon,S, Perez-Segura,MC, Serrano,A, Antequera-González,B, Alonso-Piñero,JA, González-Rovira,A, Extremera-García,MJ, Durán-Ruiz,MC] Biomedicine, Biotechnology and Public Health Department, Cádiz University, Cadiz, Spain. [Beltran-Camacho,L, Durán-Ruiz,MC] Institute of Biomedical Research Cadiz (INIBICA), Cadiz, Spain. [Rodriguez-Piñero,M] Angiology & Vascular Surgery Unit, Hospital Universitario Puerta del Mar, Cádiz, Spain. [Moreno-Luna,R] Laboratory of Neuroinflammation, Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain. [Larsen,MR] Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark., This study was supported by the Institute of Health Carlos III, ISCIII (PI16-00784) and the 'Programa Operativo de Andalucia FEDER, Iniciativa Territorial Integrada ITI 2014-2020 Consejeria de Salud, Junta de Andalucia (PI0026-2017).
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Proteomics
Pathology
Angiogenesis
medicine.medical_treatment
Cell- and Tissue-Based Therapy
Medicine (miscellaneous)
030204 cardiovascular system & hematology
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
Cell therapy
Mice
0302 clinical medicine
Ischemia
Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Cardiovascular Physiological Processes::Neovascularization
Physiologic [Medical Subject Headings]
Organisms::Eukaryota::Animals [Medical Subject Headings]
lcsh:QD415-436
lcsh:R5-920
Critical limb ischemia
Molecular Medicine
medicine.symptom
Stem cell
lcsh:Medicine (General)
Diseases::Cardiovascular Diseases::Vascular Diseases::Peripheral Vascular Diseases::Peripheral Arterial Disease [Medical Subject Headings]
Isquemia crónica que amenaza las extremidades
Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Growth Substances::Angiogenesis Modulating Agents::Angiogenesis Inducing Agents [Medical Subject Headings]
medicine.medical_specialty
Mice
Nude
Neovascularization
Physiologic
Revascularization
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Arteriogenesis
Diseases::Pathological Conditions
Signs and Symptoms::Pathologic Processes::Ischemia [Medical Subject Headings]
lcsh:Biochemistry
03 medical and health sciences
Peripheral Arterial Disease
Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Proteomics [Medical Subject Headings]
medicine
Animals
Humans
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy [Medical Subject Headings]
Progenitor cell
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings]
business.industry
Research
Inductores de la angiogénesis
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice
Mutant Strains::Mice
Nude [Medical Subject Headings]
Cell Biology
medicine.disease
Circulating angiogenic cells
Proteómica
030104 developmental biology
business
Zdroj: Stem Cell Research & Therapy
Beltran-Camacho, L, Jimenez-Palomares, M, Rojas-Torres, M, Sanchez-Gomar, I, Rosal-Vela, A, Eslava-Alcon, S, Perez-Segura, M C, Serrano, A, Antequera-González, B, Alonso-Piñero, J A, González-Rovira, A, Extremera-García, M J, Rodriguez-Piñero, M, Moreno-Luna, R, Larsen, M R & Durán-Ruiz, M C 2020, ' Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia ', Stem Cell Research and Therapy, vol. 11, no. 1, 106 . https://doi.org/10.1186/s13287-020-01591-0
Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-20 (2020)
Stem Cell Research & Therapy (2020) 11:106
RODIN. Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz
instname
ISSN: 1757-6512
Popis: BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.
Institute of Health Carlos III, ISCIII; Junta de Andalucia
Databáze: OpenAIRE
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