Dynamic loading, matrix maintenance and cell injection therapy of human intervertebral discs cultured in a bioreactor. Rosenzweig, D. H., Gawri, R., Moir, J., Beckman, L., Eglin, D., Steffen, T., Roughley, P. J., Ouellet, J. A., & Haglund, L. European Cells and Materials, 31:26–39, 2016. doi abstract bibtex Low back pain originating from intervertebral disc (IVD) degenerationaffectsthequalityoflifeformillionsof people, and it is a major contributor to global healthcare costs. Long-term culture of intact IVDs is necessary to develop ex vivomodels of human IVD degeneration and repair, where the relationship between mechanobiology, disc matrix composition and metabolism can be better understood. Abioreactor wasdevelopedthat facilitates culture of intact human IVDs in a controlled, dynamically loaded environment. Tissue integrity and cell viability was evaluated under 3 different loading conditions: low 0.1-0.3, medium 0.1-0.6 and high 0.1-1.2 MPa. Cell viability was maintained > 80 % throughout the disc at low and medium loads, whereas it dropped to approximately 70 % (NP) and 50 % (AF) under high loads. Although cell viability was affected at high loads, there was no evidence of sGAG loss, changes in newly synthesised collagen type II or chondroadherin fragmentation. Sulphated GAG content remained at a stable level of approximately 50 µg sGAG/mg tissue in all loading protocols. To evaluate the feasibility oftissuerepairstrategieswithcellsupplementation, human NP cells were transplanted into discs within a thermoreversible hyaluronan hydrogel. The discs were loaded under medium loads, and the injected cells remained largely localised to the NP region. This study demonstrates the feasibility of culturing human IVDs for 14 days under cyclic dynamic loading conditions. The system allows the determination a safe range-of-loading and presents a platform to evaluate cell therapies and help to elucidate the effect of load following cell-based therapies.
@article{Rosenzweig201626,
abstract = {Low back pain originating from intervertebral disc (IVD) degenerationaffectsthequalityoflifeformillionsof people, and it is a major contributor to global healthcare costs. Long-term culture of intact IVDs is necessary to develop ex vivomodels of human IVD degeneration and repair, where the relationship between mechanobiology, disc matrix composition and metabolism can be better understood. Abioreactor wasdevelopedthat facilitates culture of intact human IVDs in a controlled, dynamically loaded environment. Tissue integrity and cell viability was evaluated under 3 different loading conditions: low 0.1-0.3, medium 0.1-0.6 and high 0.1-1.2 MPa. Cell viability was maintained > 80 % throughout the disc at low and medium loads, whereas it dropped to approximately 70 % (NP) and 50 % (AF) under high loads. Although cell viability was affected at high loads, there was no evidence of sGAG loss, changes in newly synthesised collagen type II or chondroadherin fragmentation. Sulphated GAG content remained at a stable level of approximately 50 µg sGAG/mg tissue in all loading protocols. To evaluate the feasibility oftissuerepairstrategieswithcellsupplementation, human NP cells were transplanted into discs within a thermoreversible hyaluronan hydrogel. The discs were loaded under medium loads, and the injected cells remained largely localised to the NP region. This study demonstrates the feasibility of culturing human IVDs for 14 days under cyclic dynamic loading conditions. The system allows the determination a safe range-of-loading and presents a platform to evaluate cell therapies and help to elucidate the effect of load following cell-based therapies.},
annote = {cited By 10},
author = {Rosenzweig, D. H. and Gawri, R. and Moir, J. and Beckman, L. and Eglin, D. and Steffen, T. and Roughley, P. J. and Ouellet, J. A. and Haglund, Lisbet},
doi = {10.22203/eCM.v031a03},
issn = {14732262},
journal = {European Cells and Materials},
keywords = {Bioreactor,Cell therapy,Dynamic loading,Hydrogel,Intervertebral discs,Organ culture,Tissue regeneration},
pages = {26--39},
pmid = {26728497},
title = {{Dynamic loading, matrix maintenance and cell injection therapy of human intervertebral discs cultured in a bioreactor}},
volume = {31},
year = {2016}
}
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Long-term culture of intact IVDs is necessary to develop ex vivomodels of human IVD degeneration and repair, where the relationship between mechanobiology, disc matrix composition and metabolism can be better understood. Abioreactor wasdevelopedthat facilitates culture of intact human IVDs in a controlled, dynamically loaded environment. Tissue integrity and cell viability was evaluated under 3 different loading conditions: low 0.1-0.3, medium 0.1-0.6 and high 0.1-1.2 MPa. Cell viability was maintained > 80 % throughout the disc at low and medium loads, whereas it dropped to approximately 70 % (NP) and 50 % (AF) under high loads. Although cell viability was affected at high loads, there was no evidence of sGAG loss, changes in newly synthesised collagen type II or chondroadherin fragmentation. Sulphated GAG content remained at a stable level of approximately 50 µg sGAG/mg tissue in all loading protocols. 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