Department of Ophthalmology, Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Hospital, Chongqing, 400038, China.
Department of Anatomy, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, Burn and Combined injury, Department of Plastic and Aesthetic Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
Stem Cell Res Ther. 2020 Nov 25;11(1):495. doi: 10.1186/s13287-020-01986-z.
Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell transplants have served as a cell therapy for treating retinal degenerative diseases. However, how to optimize the survival and engraftment of hESC-RPE cells is a great challenge.
Here, we report hESC-RPE cells that are embedded with polyelectrolytes gelatin and alginate by layer-by-layer (LbL) self-assembly technique, based on the opposite charge of alternate layers. Cells were assessed for cell survival, immunogenicity, and function in vitro and in vivo.
This strategy obviously decreased the immunogenicity of hESC-RPE cells without affecting its activity. LbL-RPE cell transplants into the subretinal space of Royal College of Surgeons (RCS) rats optimized cell engraftment and decreased immunogenicity compared to untreated RPE cell transplants (immunosuppression was not used during the 21-week study). Visual-functional assay with electroretinogram recordings (ERGs) also showed higher B wave amplitudes in RCS rats with LbL-RPE cell transplants.
We demonstrate that transplanted LbL-RPE cells have better viability and grafting efficiency, optimized immunogenicity, and visual function. Therefore, LbL engineering is a promising method to increase the efficacy of hESC-RPE cell transplantation.
人胚胎干细胞衍生的视网膜色素上皮(hESC-RPE)细胞移植已作为治疗视网膜退行性疾病的细胞疗法。然而,如何优化 hESC-RPE 细胞的存活和移植仍然是一个巨大的挑战。
在这里,我们报告了通过层层(LbL)自组装技术将带有聚电解质明胶和藻酸盐的 hESC-RPE 细胞嵌入的方法,该技术基于交替层的相反电荷。评估了细胞在体外和体内的细胞存活、免疫原性和功能。
与未处理的 RPE 细胞移植相比,该策略明显降低了 hESC-RPE 细胞的免疫原性,而不影响其活性(在 21 周的研究中未使用免疫抑制)。与未经处理的 RPE 细胞移植相比,LbL-RPE 细胞移植到皇家外科医生学院(RCS)大鼠的视网膜下腔中优化了细胞移植和降低了免疫原性。通过视网膜电图记录(ERGs)进行的视觉功能检测也显示出 LbL-RPE 细胞移植的 RCS 大鼠的 B 波幅度更高。
我们证明了移植的 LbL-RPE 细胞具有更好的活力和移植效率、优化的免疫原性和视觉功能。因此,LbL 工程是提高 hESC-RPE 细胞移植疗效的一种很有前途的方法。