Thermosensitive hydrogels loaded with human-induced pluripotent stem cells overexpressing growth differentiation factor-5 ameliorate intervertebral disc degeneration in rats.
Annan HuRong XingLibo JiangZefang LiPeng LiuHoulei WangXilei LiJian DongPublished in: Journal of biomedical materials research. Part B, Applied biomaterials (2020)
To evaluate the effects of thermosensitive hydrogels loaded with human-induced pluripotent stem cells transfected with the growth differentiation factor-5 (GDF5-hiPSCs) on rat intervertebral disc regeneration. GDF5-hiPSCs were cocultured with rat nucleus pulposus (NP) cells in vitro. Real-time PCR and western blot were used to determine the differentiation of hiPSCs. Rat caudal intervertebral discs were punctured using a needle under X-ray, and groups of coccygeal (Co) discs were subject to various treatments: Puncture group (Co6/7, punctured without treatment); Hydrogel group (Co7/8, 2 μl of hydrogel injected without cells); GDF5-hiPSCs + Hydrogel group (Co8/9, 2 μl of GDF5-hiPSCs-loaded hydrogel injected); and Normal control (Co5/6). X-ray, MRI, and histological evaluations were performed at 1, 2, and 3 months after cell transplantation and relative changes in the disc height index (DHI%) and voxel count were calculated and compared. GDF5-hiPSCs were successfully differentiated to a chondrogenic linage after cocultured with rat NP cells. In terms of X-ray, MRI, and HE staining scores, the GDF5-hiPSCs + Hydrogel group was significantly superior to the Puncture and Hydrogel groups (p < .05). Compared with the Normal group, the MRI-based voxel count of the GDF5-hiPSCs + Hydrogel group was significantly lower at 1, 2, and 3 months after cell transplantation (p < .05). However, there were no significant differences in histological scores at 1 and 2 months after cell transplantation compared with the Normal group (p > .05). In conclusion, thermosensitive hydrogel-encapsulated hiPSCs overexpressing the GDF5 gene ameliorated intervertebral disc degeneration.
Keyphrases
- drug delivery
- wound healing
- induced pluripotent stem cells
- hyaluronic acid
- tissue engineering
- induced apoptosis
- cell therapy
- cancer therapy
- oxidative stress
- cell cycle arrest
- endothelial cells
- drug release
- magnetic resonance imaging
- single cell
- high resolution
- contrast enhanced
- body mass index
- real time pcr
- ultrasound guided
- gene expression
- physical activity
- south africa
- dna methylation
- extracellular matrix
- endoplasmic reticulum stress
- dual energy
- transcription factor
- mass spectrometry