Owing to the tissue characteristics of tendons with few blood vessels and cells, the regeneration and repair of injured tendons can present a considerable challenge, which considerably affects the motor function of limbs and leads to serious physical and mental pain, along with an economic burden on patients. Herein, we designed and fabricated a dipeptide hydrogel (DPH) using polypeptides P11-4 and P11-8. This hydrogel exhibited self-assembly characteristics and could be administered in vitro. To endow the hydrogel with differentiation and regeneration abilities, we added different concentrations of growth differentiation factor 5 (GDF5) to form GDF5@DPH. GDF5@DPH promoted the aggregation and differentiation of tendon stem/progenitor cells and promoted the regeneration and repair of tendon cells and collagen fibers in injured areas. In addition, GDF5@DPH inhibited inflammatory reactions in the injured area. Owing to its injectable properties, DPH can jointly inhibit adhesion and scar hyperplasia between tissues caused by endogenous inflammation and exogenous surgery and can provide a favorable internal environment for the regeneration and repair of the injured area. Overall, the GDF5@DPH system exhibits considerable promise as a novel approach to treating tendon injury.

2020-07-01·Journal of Biomedical Materials Research Part B: Applied Biomaterials

Thermosensitive hydrogels loaded with human‐induced pluripotent stem cells overexpressing growth differentiation factor‐5 ameliorate intervertebral disc degeneration in rats

Article

作者: Xing, Rong ; Hu, Annan ; Li, Xilei ; Jiang, Libo ; Liu, Peng ; Li, Zefang ; Dong, Jian ; Wang, Houlei

AbstractTo 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.

2020-07-01·Journal of Cellular and Molecular Medicine2区 · 医学

The GDF‐5 mutant M1673 exerts robust anabolic and anti‐catabolic effects in chondrocytes

2区 · 医学

ArticleOA

作者: Mang, Tanja ; Kleinschmidt‐Dörr, Kerstin ; Gigout, Anne ; Ploeger, Frank ; Lindemann, Sven

AbstractThe growth and differentiation factor 5 (GDF‐5) is known to play a key role in cartilage morphogenesis and homeostasis, and a single‐nucleotide polymorphism in its promoter sequence was found to be associated with osteoarthritis (OA). In addition, GDF‐5 was shown to promote extracellular matrix (ECM) production in healthy chondrocytes, to stimulate chondrogenesis of mesenchymal stem cells (MSCs) and to protect against OA progression in vivo. Therefore, GDF‐5 appears to be a promising treatment for osteoarthritis. However, GDF‐5 also promotes osteogenesis and hypertrophy, limiting its therapeutic utility. To circumvent this, a GDF‐5 mutant with lower hypertrophic and osteogenic properties was engineered: M1673. The present study aimed to evaluate and compare the effects of GDF‐5 and M1673 on primary porcine and human OA chondrocytes. We found that both GDF‐5 and M1673 can robustly stimulate ECM accumulation, type II collagen and aggrecan expression in porcine and human OA chondrocytes in 3D culture. In addition, both molecules also down‐regulated MMP13 and ADAMTS5 expression. These results suggest that M1673 retained the anabolic and anti‐catabolic effects of GDF‐5 on chondrocytes and is an alternative to GDF‐5 for osteoarthritis.

100 项与 M-1673 相关的药物交易

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