Abstract

Lumbar degenerative disc diseases cause low back pain (LBP). The maintenance of the height and stability of the intervertebral disc (IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration (IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus (NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy (PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β. Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.

Highlights

  • Low back pain (LBP) is a major cause of disability among elderly individuals and imposes substantial social and economic burden on societies worldwide.[1]

  • Significant improvement was observed in Clinically, we have found that fibrosis of the intervertebral disc (IVD) after Percutaneous endoscopic lumbar discectomy (PELD) can degenerative status in DFb-treated IVDs at 3 months compared lead to stability of the spine

  • In the IVD groups injected with allogenic GFP−ve fibroblasts, we found a mixed population of autologous nucleus pulposus (NP) cells that were GFP+ve and FSP1−ve as well as GFP+ve and FSP1+ve NP cells that had differentiated towards a fibrotic phenotype

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Summary

1234567890();,: INTRODUCTION

Low back pain (LBP) is a major cause of disability among elderly individuals and imposes substantial social and economic burden on societies worldwide.[1]. We fibroblasts (DFbs) can integrate well into tissue defects and can confirmed similar improvements in disc height and degenerative accelerate fibrosis and tissue healing.[11] In addition to their ease scores at shorter time frames of 2 and 4 weeks after puncture of accessibility, DFbs have gained much attention for use in cell surgery. The results from our in vivo rat IVD degenerative independent studies have shown the potential for DFbs in the model showed that the injection of DFbs or the L929 murine treatment of intervertebral disc degeneration and inflammation in rabbit models.[14,15] fibroblastic cell line into the IVDs following needle puncture could maintain IVD height, reduce osteophyte formation in the adjacent.

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