(F1111) Evaluation of Injectable Adipose Stem Cell-Derived Micro-Cartilage Hydrogel for Regenerative Treatment of Lumbar Disc Herniation Using a Novel Preclinical Model

Abstract: Lumbar Disc Herniation (LDH), primarily caused by intervertebral disc degeneration (IDD), affects 10-20% of the population globally, leading to pain and disability. Available treatments mainly focus on symptom management.
Stem cell therapies hold promise for treating LDH but often show low recovery rates and poor in vivo remodeling. Current implantation techniques for tissue-engineered lumbar discs or nucleus pulposus face challenges due to the spine's complex, load-bearing structure, particularly in LDH patients. The lack of effective in vitro and in vivo models for LDH limits progress in regenerative therapy research.
To address these challenges, we developed an injectable platelet-rich plasma (PRP) micro-cartilage hydrogel (PAM) containing adipose stem cell-derived chondrogenic cell masses (ASCC) under 1 mm in diameter and in situ cross-linkable PRP. Additionally, we developed a novel rat spine motion segment LDH load-bearing model (rSMS-LDH), which was combined with an in vitro 'sandwich' model and an in vivo rabbit LDH model to validate PAM’s integrability and remodeling ability in the intervertebral disc.
Histological and immunofluorescent staining results showed that PAM integrates well with the nucleus pulposus and fibrosis, with less cell leakage and better cartilage-like extracellular matrix (ECM) formation compared to the PRP stem cell hydrogel (PSH) in vitro. Although both PAM and PSH showed therapeutic benefits in four-week animal studies, the PAM group demonstrated enhanced anti-ferroptosis effects and more consistent ECM production, which are crucial for cell survival in the harsh disc microenvironment and long-term intervertebral disc repair.
This study revealed that PRP micro-cartilage hydrogel provides better niche-rebuilding conditions in the harsh intervertebral environment. This minimally invasive injectable hydrogel could transform the management of LDH. The rat SMS-LDH ‘spine organoid’ avoids inhumane LDH generation methods and offers a valuable preclinical model for LDH regenerative treatments.

Funding Source: Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital

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