Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell

Abstract

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration (IVDD). However, the increased levels of reactive oxygen species (ROS) in the degenerated region will impede the efficiency of human adipose-derived stem cells (human ADSCs) transplantation therapy. It inhibits human ADSCs proliferation, and increases human ADSCs apoptosis. Herein, we firstly devised a novel amphiphilic copolymer PEG-PAPO, which could self-assemble into a nanosized micelle and load lipophilic kartogenin (KGN), as a single complex (PAKM). It was an injectable esterase-responsive micelle, and showed controlled release ability of KGN and apocynin (APO). Oxidative stimulation promoted the esterase activity in human ADSCs, which accelerate degradation of esterase-responsive micelle. Compared its monomer, the PAKM micelle possessed better bioactivities, which were attributed to their synergistic effect. It enhanced the viability, autophagic activation (P62, LC3 II), ECM-related transcription factor (SOX9), and ECM (Collagen II, Aggrecan) maintenance in human ADSCs. Furthermore, it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats. Therefore, PAKM micelles perform promoting cell survival and differentiation effects, and may be a potential therapeutic agent for IVDD.

Pretreatment of nucleus pulposus mesenchymal stem cells with appropriate concentration of H2O2 enhances their ability to treat intervertebral disc degeneration

“…The parameters were as follows: Modality (X-Ray), Background (None), Illumination (X-Ray), Filters (X-Ray 0.4 mm, KVP 45, Excitation 0, Emission 0), Exposure time (1.2 s), FOV (15CM), fStop (2), Bin (1 × 1), Focal Plane (0 mm), and Focal Zone (X-Ray). Finally, ImageJ was used to measure the three longitudinal lines of the intervertebral disc and the two adjacent upper and lower vertebral bodies, and then the DHI% was calculated according to the method recorded in previous research [ 9 ] to evaluate the degree of intervertebral disc degeneration.…”

“…Stem cell transplantation has become a promising therapeutic method utilized to treat IVDD experimentally and clinically in recent years [ 7 , 8 ]. The intervertebral disc is recognized as an immune-exempt area, and this feature makes it possible to use exogenous stem cells to treat IVDD [ 9 , 10 ]. Extensive studies have shown that a variety of stem cells can directly differentiate into nucleus pulposus cells and facilitate the function of degenerative nucleus pulposus cells in a paracrine manner when transplanted into the degenerative intervertebral disc [ 11 – 14 ].…”

Pretreatment of NPMSCs with Appropriate Concentration of H2O2 Enhances its Ability to Treat IVDD

“…The parameters were as follows: Modality (X-Ray), Background (None), Illumination (X-Ray), Filters (X-Ray 0.4 mm, KVP 45, Excitation 0, Emission 0), Exposure time (1.2 s), FOV (15 cm), fStop (2), Bin (1×1), Focal Plane (0 mm), Focal Zone (X-Ray). Finally, Image J was used to measure the three longitudinal lines of the intervertebral disc and the two adjacent upper and lower vertebral bodies, and then calculate the DHI% according to the method recorded in previous research [9] to evaluate the degree of IVDD.…”

“…Stem cell transplantation has become a promising therapeutic method utilized to treat IVDD experimentally and clinically in recent years [7,8]. The intervertebral disc is recognized as an immuneexempt area, and this feature makes it possible to use exogenous stem cells to treat IVDD [9,10]. Extensive researches have shown that a variety of stem cells can directly differentiate into nucleus pulposus cells, and facilitate the function of degenerative nucleus pulposus cells through a paracrine manner when transplanted into the degenerative intervertebral disc [11][12][13][14].…”

Single-Dose Intra-Cartilage Delivery of Kartogenin Using a Cationic Multi-Arm Avidin Nanocarrier Suppresses Cytokine-Induced Osteoarthritis-Related Catabolism

“…Particle and gel-based systems are under consideration for enhancing intra-joint residence time of small molecule drugs like KGN but none of these delivery methods enable cartilage targeting or penetration. 18 , 24 , 27 - 29 …”