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Oxygen effects on senescence in chondrocytes and mesenchymal stem cells: consequences for tissue engineering.
Iowa Orthop J 2004; 24:15-20IO

Abstract

Primary isolates of chondrocytes and mesenchymal stem cells are often insufficient for cell-based autologous grafting procedures, necessitating in vitro expansion of cell populations. However, the potential for expansion is limited by cellular senescence, a form of irreversible cell cycle arrest regulated by intrinsic and extrinsic factors. Intrinsic mechanisms common to most somatic cells enforce senescence at the so-called "Hayflick limit" of 60 population doublings. Termed "replicative senescence", this mechanism prevents cellular immortalization and suppresses oncogenesis. Although it is possible to overcome the Hayflick limit by genetically modifying cells, such manipulations are regarded as prohibitively dangerous in the context of tissue engineering. On the other hand, senescence associated with extrinsic factors, often called "stress-induced" senescence, can be avoided simply by modifying culture conditions. Because stress-induced senescence is "premature" in the sense that it can halt growth well before the Hayflick limit is reached, growth potential can be significantly enhanced by minimizing culture related stress. Standard culture techniques were originally developed to optimize the growth of fibroblasts but these conditions are inherently stressful to many other cell types. In particular, the 21% oxygen levels used in standard incubators, though well tolerated by fibroblasts, appear to induce oxidative stress in other cells. We reasoned that chondrocytes and MSCs, which are adapted to relatively low oxygen levels in vivo, might be sensitive to this form of stress. To test this hypothesis we compared the growth of MSC and chondrocyte strains in 21% and 5% oxygen. We found that incubation in 21% oxygen significantly attenuated growth and was associated with increased oxidant production. These findings indicated that sub-optimal standard culture conditions sharply limited the expansion of MSC and chondrocyte populations and suggest that cultures for grafting purposes should be maintained in a low-oxygen environment.

Authors+Show Affiliations

Department of Orthopaedics and Rehabilitation, The University of Iowa, IA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15296200

Citation

Moussavi-Harami, Farid, et al. "Oxygen Effects On Senescence in Chondrocytes and Mesenchymal Stem Cells: Consequences for Tissue Engineering." The Iowa Orthopaedic Journal, vol. 24, 2004, pp. 15-20.
Moussavi-Harami F, Duwayri Y, Martin JA, et al. Oxygen effects on senescence in chondrocytes and mesenchymal stem cells: consequences for tissue engineering. Iowa Orthop J. 2004;24:15-20.
Moussavi-Harami, F., Duwayri, Y., Martin, J. A., Moussavi-Harami, F., & Buckwalter, J. A. (2004). Oxygen effects on senescence in chondrocytes and mesenchymal stem cells: consequences for tissue engineering. The Iowa Orthopaedic Journal, 24, pp. 15-20.
Moussavi-Harami F, et al. Oxygen Effects On Senescence in Chondrocytes and Mesenchymal Stem Cells: Consequences for Tissue Engineering. Iowa Orthop J. 2004;24:15-20. PubMed PMID: 15296200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxygen effects on senescence in chondrocytes and mesenchymal stem cells: consequences for tissue engineering. AU - Moussavi-Harami,Farid, AU - Duwayri,Yazan, AU - Martin,James A, AU - Moussavi-Harami,Farshid, AU - Buckwalter,Joseph A, PY - 2004/8/7/pubmed PY - 2004/8/25/medline PY - 2004/8/7/entrez SP - 15 EP - 20 JF - The Iowa orthopaedic journal JO - Iowa Orthop J VL - 24 N2 - Primary isolates of chondrocytes and mesenchymal stem cells are often insufficient for cell-based autologous grafting procedures, necessitating in vitro expansion of cell populations. However, the potential for expansion is limited by cellular senescence, a form of irreversible cell cycle arrest regulated by intrinsic and extrinsic factors. Intrinsic mechanisms common to most somatic cells enforce senescence at the so-called "Hayflick limit" of 60 population doublings. Termed "replicative senescence", this mechanism prevents cellular immortalization and suppresses oncogenesis. Although it is possible to overcome the Hayflick limit by genetically modifying cells, such manipulations are regarded as prohibitively dangerous in the context of tissue engineering. On the other hand, senescence associated with extrinsic factors, often called "stress-induced" senescence, can be avoided simply by modifying culture conditions. Because stress-induced senescence is "premature" in the sense that it can halt growth well before the Hayflick limit is reached, growth potential can be significantly enhanced by minimizing culture related stress. Standard culture techniques were originally developed to optimize the growth of fibroblasts but these conditions are inherently stressful to many other cell types. In particular, the 21% oxygen levels used in standard incubators, though well tolerated by fibroblasts, appear to induce oxidative stress in other cells. We reasoned that chondrocytes and MSCs, which are adapted to relatively low oxygen levels in vivo, might be sensitive to this form of stress. To test this hypothesis we compared the growth of MSC and chondrocyte strains in 21% and 5% oxygen. We found that incubation in 21% oxygen significantly attenuated growth and was associated with increased oxidant production. These findings indicated that sub-optimal standard culture conditions sharply limited the expansion of MSC and chondrocyte populations and suggest that cultures for grafting purposes should be maintained in a low-oxygen environment. SN - 1541-5457 UR - https://www.unboundmedicine.com/medline/citation/15296200/Oxygen_effects_on_senescence_in_chondrocytes_and_mesenchymal_stem_cells:_consequences_for_tissue_engineering_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/15296200/ DB - PRIME DP - Unbound Medicine ER -