Special Poster Session 51st International Society for the Study of the Lumbar Spine Annual Meeting 2025

Evaluating hyaluronic acid and alginate as biomaterial carriers for nucleus pulposus cell transplantation in a canine disc degeneration model (114350)

Jordy Schol 1 , Shota Ogasawara 1 , Takayuki Warita 2 , Yoshihiko Nakamura 2 , Erika Matsushita 1 , Kosuke Sako 1 , Shota Tamagawa 3 , Hazuki Soma 1 2 , Daisuke Sakai 1 , Mastao Sato 1 , Masahiko Watanabe 1
  1. Tokai University School of Medicine, Isehara, Japan
  2. TUNZ Pharma Inc., Osaka, Japan
  3. Juntendo University School of Medicine, Tokyo, Japan

INTRODUCTION

Degeneration of the intervertebral disc (IDD) is a common source of chronic low back pain (LBP) and remains the leading cause of disability. Regenerative treatments, especially cell therapies, has shown promise for reducing LBP and potentially reversing the degenerative state of discs.1 This research investigates the effectiveness of two biomaterials, hyaluronic acid (HA) and alginate, used as carriers for transplanting nucleus pulposus (NP) cells within a canine IDD model, with the goal of enhancing regenerative outcomes.

 

METHODS

Human NP cells were isolated and cultured with optimization for Tie2-positive cell proportions2, preparing them for an off-the-shelf transplantation product 3,4. IDD was induced in ten female beagle dogs at spinal levels L3/L4-L5/L6, following a previously established protocol5, two weeks before transplantation. The degenerative discs were randomly treated with either hyaluronic acid (HA) or alginate, with or without cells. Discs injected with saline served as a degenerative sham control. Following a 12-week monitoring period with monthly disc height index (DHI) measurements and MRI T2-weighted scans ended with disc explantation and histological examinations. Histological specimens were scored using the ORS Spine large animal classification scheme.6 All data was anal

 

RESULTS

The induced IDD led to comparable losses in DHI and T2-relaxation times across samples at the time of transplantation. (Fig 1A-C)Twelve weeks post-transplant, both HA and alginate carriers proved effective in mitigating degeneration relative to the saline control. HA-loaded NP cells consistently demonstrated superior outcomes in DHI and MRI hydration measurements, significantly outperforming the sham group and indicating strong support for NP cell activity. Histological analysis reinforced these results (Fig 1D-E), showing better preservation of disc structure in the HA groups. While alginate also showed regenerative potential, results suggested it was less reliable in maintaining disc integrity compared to HA.

 

DISCUSSION

This research underscores the potential of these clinically relevant biomaterials as carriers in enhancing cell-based therapies for IDD. HA exhibited a stronger ability to support the regenerative functions of NP cells, positioning it as an attractive option for clinical applications. It is important to note that the induced degeneration was relatively mild, suggesting that further refinement of the canine model may be advantageous. Additionally, our results suggest that optimizing the combinations of biomaterials and cells could improve therapeutic outcomes for patients suffering from IDD-associated LBP.

 

FIGURE 1. Overview of (A) Disc height index (DHI) and (B) T2 relaxation time change compared to degenerative values (week 0). (C) Example of T2 map images at week 0 and 12 post-transplantation. (D) Histological cores and (E) safranin-O/Fast green stained section examples. * p<0.05, ** p<0.01. Bars represent mean values, dots represent individual measurements, and error bars represent standard deviations.

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  6. Lee NN, et al. (2021). A comprehensive tool box for large animal studies of intervertebral disc degeneration. JOR Spine, 4(2), e1162. https://doi.org/10.1002/jsp2.1162