An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration(IDD).Current limitations of stem cells include with their insufficient cell source,poor proliferation capacity,low nucleus pulposus(NP)-specific differentiation potential,and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation.To address these challenges,embryo-derived long-term expandable nucleus pulposus progenitor cells(NPPCs)and esterase-responsive ibuprofen nano-micelles(PEG-PIB)were prepared for synergistic transplantation.In this study,we propose a biomaterial pre-modification cell strategy;the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis.The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro;their further synergistic transplantation yielded effective functional recovery,histological regeneration,and inhibition of pyroptosis during IDD regeneration.Herein,we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

Spinal cord decompression reduces rat neural cell apoptosis secondary to spinal cord injury

Objective:To determine whether spinal cord decompression plays a role in neural cell apoptosis after spinal cord injury. Study design:We used an animal model of compressive spinal cord injury with incomplete paraparesis to evaluate neural cell apoptosis after decompression. Apoptosis and cellular damage were assessed by staining with terminal deoxynucleotidyl transferase(TdT)-mediated deoxyuridine triphosphate nick-end labelling(TUNEL) and immunostaining for caspase-3,Bcl-2 and Bax. Methods:Experiments were conducted in male Sprague-Dawley rats(n=78) weighing 300～400 g. The spinal cord was compressed posteriorly at T10 level using a custom-made screw for 6 h,24 h or continuously,followed by decompression by removal of the screw. The rats were sacrificed on Day 1 or 3 or in Week 1 or 4 post-decompression. The spinal cord was removed en bloc and examined at lesion site,rostral site and caudal site(7.5 mm away from the lesion). Results:The numbers of TUNEL-positive cells were significantly lower at the site of decompression on Day 1,and also at the rostral and caudal sites between Day 3 and Week 4 post-decompression,compared with the persistently compressed group. The numbers of cells between Day 1 and Week 4 were immunoreactive to caspase-3 and B-cell lymphoma-2(Bcl-2)-associated X-protein(Bax),but not to Bcl-2,correlated with those of TUNEL-positive cells. Conclusion:Our results suggest that decompression reduces neural cell apoptosis following spinal cord injury.