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Thermosensitive hydrogels loaded with human-induced pluripotent stem cells overexpressing growth differentiation factor-5 ameliorate intervertebral disc degeneration in rats.
Journal of Biomedical Materials Research Part B: Applied Biomaterials ( IF 3.2 ) Pub Date : 2020-01-12 , DOI: 10.1002/jbm.b.34541
Annan Hu 1 , Rong Xing 1 , Libo Jiang 1 , Zefang Li 1 , Peng Liu 1 , Houlei Wang 1 , Xilei Li 1 , Jian Dong 1
Affiliation  

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.

中文翻译:

载有过表达生长分化因子-5 的人诱导多能干细胞的热敏水凝胶可改善大鼠的椎间盘退变。

评估载有转染生长分化因子-5 (GDF5-hiPSCs) 的人诱导多能干细胞的热敏水凝胶对大鼠椎间盘再生的影响。GDF5-hiPSCs 在体外与大鼠髓核(NP)细胞共培养。实时 PCR 和蛋白质印迹用于确定 hiPSC 的分化。大鼠尾椎间盘在X线下用针穿刺,尾骨(Co)椎间盘组进行不同处理:穿刺组(Co6/7,穿刺未处理);水凝胶组(Co7/8,2 μl 无细胞注射的水凝胶);GDF5-hiPSCs + 水凝胶组(Co8/9,注入 2 μl 的 GDF5-hiPSCs 水凝胶);和正常对照 (Co5/6)。X 射线、MRI 和组织学评估在 1、2、和细胞移植后3个月,计算和比较椎间盘高度指数(DHI%)和体素计数的相对变化。GDF5-hiPSCs 与大鼠 NP 细胞共培养后成功分化为软骨细胞系。在 X 线、MRI 和 HE 染色评分方面,GDF5-hiPSCs + Hydrogel 组显着优于穿刺组和 Hydrogel 组。p < .05)。与正常组相比,GDF5-hiPSCs + Hydrogel 组的基于 MRI 的体素计数在细胞移植后 1、2 和 3 个月显着降低(p < .05)。然而,与正常组相比,细胞移植后 1 个月和 2 个月的组织学评分没有显着差异(p > .05)。总之,过表达 GDF5 基因的热敏水凝胶封装的 hiPSC 可改善椎间盘退变。
更新日期:2020-01-12
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