Survival and function of mesenchymal stem cells (MSCs) depend on glucose to overcome exposure to long-term, severe and continuous hypoxia

Autor: B. David, Delphine Logeart-Avramoglou, C. Collet, Mickael Deschepper, Karim Oudina, V. Myrtil, Morad Bensidhoum, Hervé Petite
Přispěvatelé: Bioingénierie et Bioimagerie Ostéo-articulaires, Biomécanique et Biomatériaux Ostéo-Articulaires (B2OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de mécanique des sols, structures et matériaux (MSSMat), CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA), Physiologie intégrative, cellulaire et moléculaire (PICM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Programmed cell death
Cell Survival
[SDV]Life Sciences [q-bio]
Ischemia
ischemia
Biology
bone
Andrology
[PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph]
03 medical and health sciences
0302 clinical medicine
Adenosine Triphosphate
Tissue engineering
In vivo
marrow stromal cells
[SPI.MECA.MEMA]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanics of materials [physics.class-ph]
medicine
Animals
Viability assay
Lactic Acid
ComputingMilieux_MISCELLANEOUS
Cells
Cultured
030304 developmental biology
0303 health sciences
mesenchymal stem cells
Sheep
Tissue Engineering
Tissue Scaffolds
hypoxia
Mesenchymal stem cell
Cell Biology
Articles
Hypoxia (medical)
medicine.disease
Hypoxia-Inducible Factor 1
alpha Subunit
Cell Hypoxia
Transplantation
Oxygen
Glucose
030220 oncology & carcinogenesis
Immunology
Molecular Medicine
medicine.symptom
Zdroj: Journal of Cellular and Molecular Medicine
Journal of Cellular and Molecular Medicine, Wiley Open Access, 2011, 15 (7), pp.1505-1514. ⟨10.1111/j.1582-4934.2010.01138.x⟩
ISSN: 1582-4934
1582-1838
DOI: 10.1111/j.1582-4934.2010.01138.x⟩
Popis: Use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for various diseases but has generated marginally successful results. A consistent finding of most studies is massive death of transplanted cells. The present study examined the respective roles of glucose and continuous severe hypoxia on MSC viability and function with respect to bone tissue engineering. We hereby demonstrate for the first time that MSCs survive exposure to long-term (12 days), severe (pO2 < 1.5 mmHg) hypoxia, provided glucose is available. To this end, an in vitro model that mimics the hypoxic environment and cell-driven metabolic changes encountered by grafted sheep cells was established. In this model, the hallmarks of hypoxia (low pO2, hypoxia inducible factor-1α expression and anaerobic metabolism) were present. When conditions switched from hypoxic (low pO2) to ischemic (low pO2 and glucose depletion), MSCs exhibited shrinking, decreased cell viability and ATP content due to complete exhaustion of glucose at day 6; these results provided evidence that ischemia led to the observed massive cell death. Moreover, MSCs exposed to severe, continuous hypoxia, but without any glucose shortage, remained viable and maintained both their in vitro proliferative ability after simulation with blood reperfusion at day 12 and their in vivo osteogenic ability. These findings challenge the traditional view according to which severe hypoxia per se is responsible for the massive MSC death observed upon transplantation of these cells and provide evidence that MSCs are able to withstand exposure to severe, continuous hypoxia provided that a glucose supply is available.
Databáze: OpenAIRE
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