Evaluation of Tissue Repair Using MRI Imaging of Human Intervertebral Discs Cultured in a Bioreactor
Notice bibliographique
Résumé
Introduction Low back pain is a major problem world-wide, affecting the quality of life for millions of people. Low back pain also has a tremendous impact on direct and indirect global healthcare costs. Intervertebral disc (IVD) degeneration has been strongly associated with low back pain. Long-term organ culture of human IVDs is essential to study IVD degeneration and repair. Using an ex vivo approach, the relationship between mechanobiology, disc matrix composition and metabolism can be better understood in the context of degenerative disease. We have developed a bioreactor where intact human discs can be cultured in a controlled dynamically loaded environment. Here, we aimed to determine the most suitable loading parameters for human discs culture by assessing IVD tissue integrity and cell viability under low, medium and high magnitude cyclic load. Furthermore, we investigated the suitability of this model toward cell supplementation strategies for tissue repair and developed a novel, single disc MRI imaging sequence aimed at direct visualization of tissue repair. Materials and Methods Human IVDs were isolated from lumbar spine segments as previously described. Spines were obtained with consent through the Transplant Quebec Organ Donation Program from individuals who had undergone sustained brain death. Discs were cultured under 3 different loading schemes to mimic a sedentary lifestyle: low 0.1–0.3, medium 0.1–0.6 and high 0.1–1.2 MPa loads. Cell viability and matrix stability was assessed following 10 days of loading. Feasibility of cell/hydrogel implantation was determined over 14 days of medium dynamic loading. To determine whether isolated discs could be imaged by MRI, extracted individual discs were visualized for T1 and T2 signals using a novel sequence using a small animal Bruker 7.5 Tesla MRI. Results Cell viability was maintained at greater than 80% throughout the discs at low and medium loads. Viability dropped to ~60–70% throughout the discs under high loads. Proteoglycan content remained stable in all loading protocols (~50 μg sGAG/mg tissue), as did CHAD and newly synthesized collagen II protein. To test for feasibility of cell therapies in the bioreactors, NP cells combined with a hydrogel were injected into discs and cultured under medium load. 14 days after dynamic culture, the injected cells were mainly localized to the NP region with greater than 90% viability. The small animal MRI was able to obtain well-defined images of isolated discs, with details of tissue integrity and proteoglycan content. Conclusion Our ex vivo model of dynamic human IVD culture can be used as a platform on which to study mechanisms of degeneration as well as for novel avenues aimed at biological repair using bioactive substances or cell based therapies. Cells and bioactive substances can be administered within hydrogels thereby enhancing the reparative properties. Furthermore, it is feasible to assess repair potential of the therapies by comparing MRI scans pre- and post-therapy.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».