Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue
Abstract Background Nucleus pulposus (NP) cell density is orchestrated by an interplay between nutrient supply and metabolite accumulation. Physiological loading is essential for tissue homeostasis. However, dynamic loading is also believed to increase metabolic activity and could thereby interfere...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | JOR Spine |
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| Online Access: | https://doi.org/10.1002/jsp2.1240 |
| _version_ | 1797859585240858624 |
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| author | Elias Salzer Vivian H. M. Mouser Jurgen A. Bulsink Marianna A. Tryfonidou Keita Ito |
| author_facet | Elias Salzer Vivian H. M. Mouser Jurgen A. Bulsink Marianna A. Tryfonidou Keita Ito |
| author_sort | Elias Salzer |
| collection | DOAJ |
| description | Abstract Background Nucleus pulposus (NP) cell density is orchestrated by an interplay between nutrient supply and metabolite accumulation. Physiological loading is essential for tissue homeostasis. However, dynamic loading is also believed to increase metabolic activity and could thereby interfere with cell density regulation and regenerative strategies. The aim of this study was to determine whether dynamic loading could reduce the NP cell density by interacting with its energy metabolism. Methods Bovine NP explants were cultured in a novel NP bioreactor with and without dynamic loading in milieus mimicking the pathophysiological or physiological NP environment. The extracellular content was evaluated biochemically and by Alcian Blue staining. Metabolic activity was determined by measuring glucose and lactate in tissue and medium supernatants. A lactate‐dehydrogenase staining was performed to determine the viable cell density (VCD) in the peripheral and core regions of the NP. Results The histological appearance and tissue composition of NP explants did not change in any of the groups. Glucose levels in the tissue reached critical values for cell survival (≤0.5 mM) in all groups. Lactate released into the medium was increased in the dynamically loaded compared to the unloaded groups. While the VCD was unchanged on Day 2 in all regions, it was significantly reduced in the dynamically loaded groups on Day 7 (p ≤ 0.01) in the NP core, which led to a gradient formation of VCD in the group with degenerated NP milieu and dynamic loading (p ≤ 0.05). Conclusion It was demonstrated that dynamic loading in a nutrient deprived environment similar to that during IVD degeneration can increase cell metabolism to the extent that it was associated with changes in cell viability leading to a new equilibrium in the NP core. This should be considered for cell injections and therapies that lead to cell proliferation for treatment of IVD degeneration. |
| first_indexed | 2024-04-09T21:31:55Z |
| format | Article |
| id | doaj.art-d7212d7a3e59473ea77ce9604b44b2b6 |
| institution | Directory Open Access Journal |
| issn | 2572-1143 |
| language | English |
| last_indexed | 2024-04-09T21:31:55Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | JOR Spine |
| spelling | doaj.art-d7212d7a3e59473ea77ce9604b44b2b62023-03-27T08:33:00ZengWileyJOR Spine2572-11432023-03-0161n/an/a10.1002/jsp2.1240Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissueElias Salzer0Vivian H. M. Mouser1Jurgen A. Bulsink2Marianna A. Tryfonidou3Keita Ito4Orthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven The NetherlandsOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven The NetherlandsOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven The NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The NetherlandsOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven The NetherlandsAbstract Background Nucleus pulposus (NP) cell density is orchestrated by an interplay between nutrient supply and metabolite accumulation. Physiological loading is essential for tissue homeostasis. However, dynamic loading is also believed to increase metabolic activity and could thereby interfere with cell density regulation and regenerative strategies. The aim of this study was to determine whether dynamic loading could reduce the NP cell density by interacting with its energy metabolism. Methods Bovine NP explants were cultured in a novel NP bioreactor with and without dynamic loading in milieus mimicking the pathophysiological or physiological NP environment. The extracellular content was evaluated biochemically and by Alcian Blue staining. Metabolic activity was determined by measuring glucose and lactate in tissue and medium supernatants. A lactate‐dehydrogenase staining was performed to determine the viable cell density (VCD) in the peripheral and core regions of the NP. Results The histological appearance and tissue composition of NP explants did not change in any of the groups. Glucose levels in the tissue reached critical values for cell survival (≤0.5 mM) in all groups. Lactate released into the medium was increased in the dynamically loaded compared to the unloaded groups. While the VCD was unchanged on Day 2 in all regions, it was significantly reduced in the dynamically loaded groups on Day 7 (p ≤ 0.01) in the NP core, which led to a gradient formation of VCD in the group with degenerated NP milieu and dynamic loading (p ≤ 0.05). Conclusion It was demonstrated that dynamic loading in a nutrient deprived environment similar to that during IVD degeneration can increase cell metabolism to the extent that it was associated with changes in cell viability leading to a new equilibrium in the NP core. This should be considered for cell injections and therapies that lead to cell proliferation for treatment of IVD degeneration.https://doi.org/10.1002/jsp2.1240ex vivoglucoseintervertebral discmechanobiologymetabolismnutrition |
| spellingShingle | Elias Salzer Vivian H. M. Mouser Jurgen A. Bulsink Marianna A. Tryfonidou Keita Ito Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue JOR Spine ex vivo glucose intervertebral disc mechanobiology metabolism nutrition |
| title | Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue |
| title_full | Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue |
| title_fullStr | Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue |
| title_full_unstemmed | Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue |
| title_short | Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue |
| title_sort | dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue |
| topic | ex vivo glucose intervertebral disc mechanobiology metabolism nutrition |
| url | https://doi.org/10.1002/jsp2.1240 |
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