REX-001, a BM-MNC Enriched Solution, Induces Revascularization of Ischemic Tissues in a Murine Model of Chronic Limb-Threatening Ischemia
| Autor: | Marta Rojas-Torres, Margarita Jiménez-Palomares, Javier Martín-Ramírez, Lucía Beltrán-Camacho, Ismael Sánchez-Gomar, Sara Eslava-Alcon, Antonio Rosal-Vela, Sandra Gavaldá, Mª Carmen Durán-Ruiz |
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| Přispěvatelé: | [Rojas-Torres,M, Jiménez-Palomares,M, Beltrán-Camacho,L, Sánchez-Gomar,I, Eslava-Alcon,S, Rosal-Vela,A, Durán-Ruiz, MC] Biomedicine, Biotechnology and Public Health Department, Cádiz University, Cádiz, Spain. [Rojas-Torres,M, MC] Institute of Research and Innovation in Biomedical Sciences of Cadiz (INIBICA), Cádiz, Spain. [Martín-Ramírez,J, Gavaldá,S] R&D Department at Rexgenero Biosciences Sociedad Limitada (SL), Seville, Spain., This study was supported by Rexgenero Biosciences and also partly supported by the Institute of Health Carlos III, ISCIII (PI16-00784), and the Programa Operativo de Andalucia-FEDER, Iniciativa Territorial Integrada ITI 2014-2020, Consejería de Salud, Junta de Andalucía (PI0026-2017), co-funded by European Regional Development Fund A way to make Europe., Biomedicina, Biotecnología y Salud Pública |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
BM-MNC Angiogenesis medicine.medical_treatment 030204 cardiovascular system & hematology Pharmacology Diseases::Pathological Conditions Signs and Symptoms::Pathologic Processes::Ulcer [Medical Subject Headings] stem cell therapy Neovascularization angiogenesis 0302 clinical medicine Organisms::Eukaryota::Animals [Medical Subject Headings] Chronic limb-threatening ischemia bio-distribution assay lcsh:QH301-705.5 Original Research Gangrene Stem cell therapy Critical limb ischemia Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Cytological Techniques::Cell Tracking [Medical Subject Headings] Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Hemodynamics::Hemorheology::Blood Flow Velocity [Medical Subject Headings] Persons::Persons::Patients [Medical Subject Headings] medicine.anatomical_structure revascularization medicine.symptom Isquemia crónica que amenaza las extremidades critical limb ischemia Células madre Ischemia Células de la médula ósea Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models Animal::Disease Models Animal [Medical Subject Headings] Bio-distribution assay Revascularization Peripheral blood mononuclear cell 03 medical and health sciences Cell and Developmental Biology Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings] Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Orthopedic Procedures::Amputation [Medical Subject Headings] medicine Analytical Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] business.industry Anatomy::Cells::Bone Marrow Cells [Medical Subject Headings] Cell Biology Anatomy::Hemic and Immune Systems::Immune System::Bone Marrow [Medical Subject Headings] medicine.disease 030104 developmental biology lcsh:Biology (General) Anatomy::Cells::Stem Cells [Medical Subject Headings] Animales Bone marrow Tratamiento Basado en trasplante de células y tejidos business Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology Front. Cell Dev. Biol. 8:602837 RODIN: Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz Universidad de Cádiz RODIN. Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz instname Frontiers in Cell and Developmental Biology, Vol 8 (2020) |
| Popis: | Background: Bone Marrow Mononuclear Cells (BM-MNC) constitute a promising alternative for the treatment of Chronic Limb-Threatening ischemia (CLTI), a disease characterized by extensive blockade of peripheral arteries, clinically presenting as excruciating pain at rest and ischemic ulcers which may lead to gangrene and amputation. BM-MNC implantation has shown to be efficient in promoting angiogenesis and ameliorating ischemic symptoms in CLTI patients. However, the variability seen between clinical trials makes necessary a further understanding of the mechanisms of action of BM-MNC, and moreover, to improve trial characteristics such as endpoints, inclusion/exclusion criteria or drug product compositions, in order to implement their use as stem-cell therapy.Materials: Herein, the effect of REX-001, a human-BM derived cell suspension enriched for mononuclear cells, granulocytes and CD34+ cells, has been assessed in a murine model of CLTI. In addition, a REX-001 placebo solution containing BM-derived red blood cells (BM-RBCs) was also tested. Thus, 24 h after double ligation of the femoral artery, REX-001 and placebo were administrated intramuscularly to Balb-c nude mice (n:51) and follow-up of ischemic symptoms (blood flow perfusion, motility, ulceration and necrosis) was carried out for 21 days. The number of vessels and vascular diameter sizes were measured within the ischemic tissues to evaluate neovascularization and arteriogenesis. Finally, several cell-tracking assays were performed to evaluate potential biodistribution of these cells.Results: REX-001 induced a significant recovery of blood flow by increasing vascular density within the ischemic limbs, with no cell translocation to other organs. Moreover, cell tracking assays confirmed a decrease in the number of infused cells after 2 weeks post-injection despite on-going revascularization, suggesting a paracrine mechanism of action.Conclusion: Overall, our data supported the role of REX-001 product to improve revascularization and ischemic reperfusion in CLTI. |
| Databáze: | OpenAIRE |
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