1. Investigation of the effectiveness of gelatin hydrolysate in human iPS-RPE cell suspension transplantation
- Author
-
Shohei Kitahata, Michiko Mandai, Hinako Ichikawa, Yuji Tanaka, Toshika Senba, Keisuke Kajita, Sunao Sugita, Kazuaki Kadonosono, and Masayo Takahashi
- Subjects
Retinal pigment epithelium ,Suspension transplantation ,Induced pluripotent stem cells ,iPS cell therapy ,Gelatin ,Regenerative medicine ,Medicine (General) ,R5-920 ,Cytology ,QH573-671 - Abstract
Introduction: The retinal pigment epithelium (RPE) plays essential roles in maintaining retinal functions as well as choroidal capillaries and can lead to visual disorders if dysfunctional. Transplantation of human-induced pluripotent stem cell-derived RPE (hiPSC-RPE) is a promising therapy for such RPE impaired conditions including age-related macular degeneration. The challenge with cell suspension transplantation is targeted delivery of graft cells and undesired cell reflux. Gelatin hydrolysate, a soluble variant with specific molecular weight distribution, is examined in this study for its potential use in hiPSC-RPE suspension transplantation, particularly in reducing cell reflux and enhancing RPE engraftment. Methods: A retinal bleb model was created using polydimethylsiloxane (PDMS) soft lithography to quantify cellular reflux. We examined the effects of gelatin hydrolysate on the hiPSC-RPE of various aspects of cell behavior and performance such as cell viability, hypoxia reaction, morphology, induction of inflammation and immune responses. Results: Gelatin hydrolysate at 5 % concentration effectively mitigated cell reflux in vitro mimic, improved cell viability, reduced cell aggregation, and had an inhibitory effect on hypoxic reactions due to cell deposition with hiPSC-RPE. Additionally, gelatin hydrolysate did not affect cell adhesion and morphology, and decreased the expression of major histocompatibility complex class II molecules, which suggests reduced immunogenicity of hiPSC-RPE. Conclusion: Gelatin hydrolysate is considered a valuable and useful candidate for future regenerative therapies in hiPSC-RPE suspension transplantation.
- Published
- 2024
- Full Text
- View/download PDF