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Regenerative Biomaterials · 2025 · IF 8.1

Differentiation of human induced pluripotent stem cells into retinal pigment epithelium cells during culture on peptide-grafted hydrogels

Liu Jun,Liu Qian,Guo Minmei,Jiang Chengyu,Cheng Jianyang,Wang Ting,Sung Tzu-Cheng,Chou Shih-Jie,Chiou Shih-Hwa,Fan Guoping,Higuchi Akon

A variety of novel peptide-grafted hydrogels, of which peptides were derived from vitronectin (PQVTRGDVFTMP) or the laminin β4 chain (PMQKMRGDVFSP) were prepared in this study. The peptide-grafted hydrogels promoted the adhesion, proliferation, and colony formation of hiPSCs and maintained their pluripotency up to passage 5 under xeno-free conditions. We successfully generated RPE cells from hiPSCs on one of the most suitable xeno-free peptide-grafted hydrogels, KVN2CK (KGCGGKGG-PQVTRGDVFTMP), which derived from vitronectin, and confirmed the effect of these hiPSC-derived RPE cells in a rat retinal degeneration model (Royal College of Surgeons (RCS) rats) via subretinal transplantation, when we investigated functional improvements in vision in RCS rats after the transplantation of hPSC-derived RPE cells. Our novel peptide-grafted hydrogels provided a safe and robust platform for generating single-layer hiPSC-derived RPE cells under xeno-free conditions, which indicates the potential of these hydrogels for stem cell therapy for retinal degenerative diseases in future.

CAS / MDL: 59865-13-3
研究领域: 再生医学 · 干细胞研究 · 眼科
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Journal of Translational Medicine · 2023 ·Vol. 21 ·期 1 ·1-22 · IF 7.4

Comparison of retinal degeneration treatment with four types of different mesenchymal stem cells, human induced pluripotent stem cells and RPE cells in a rat retinal degeneration model

Liu Qian,Liu Jun,Guo Minmei,Sung Tzu-Cheng,Wang Ting,Yu Tao,Tian Zeyu,Fan Guoping,Wu Wencan,Higuchi Akon

Background Retinal degeneration (RD) is a group of disorders on irreversible vision loss. Multiple types of stem cells were used in clinical trials for RD treatment. However, it remains unknown what kinds of stem cells are most effective for the treatment. Therefore, we investigated the subretinal transplantation of several types of stem cells, human adipose-derived stem cells (hADSCs), amniotic fluid stem cells (hAFSCs), bone marrow stem cells (hBMSCs), dental pulp stem cells (hDPSCs), induced pluripotent stem cell (hiPSC), and hiPSC-derived retinal pigment epithelium (RPE) cells for protection effects, paracrine effects and treatment efficiency in an RD disease model rats.Methods The generation and characterization of these stem cells and hiPSC-derived RPE cells were performed before transplantation. The stem cells or hiPSC-derived RPE cell suspension labelled with CellTracker Green to detect transplanted cells were delivered into the subretinal space of 3-week-old RCS rats. The control group received subretinal PBS injection or non-injection. A series of detections including fundus photography, optomotor response (OMR) evaluations, light–dark box testing, electroretinography (ERG), and hematoxylin and eosin (HE) staining of retinal sections were conducted after subretinal injection of the cells.Results Each stem cell, hiPSC-derived RPE cell or PBS (blank experiment) was successfully transplanted into at least six RCS rats subretinally. Compared with the control rats, RCS rats subjected to subretinal transplantation of any stem cells except hiPSCs showed higher ERG waves (p < 0.05) and quantitative OMR (qOMR) index values (hADSCs: 1.166, hAFSCs: 1.249, hBMSCs: 1.098, hDPSCs: 1.238, hiPSCs: 1.208, hiPSC-RPE cells: 1.294, non-injection: 1.03, PBS: 1.06), which indicated better visual function, at 4 weeks post-injection. However, only rats that received hiPSC-derived RPE cells maintained their visual function at 8 weeks post-injection (p < 0.05). The outer nuclear layer thickness observed in histological sections after HE staining showed the same pattern as the ERG and qOMR results.Conclusion sCompared to hiPSC-derived RPE cells, adult and fetal stem cells yielded improvements in visual function for up to 4 weeks post-injection; this outcome was mainly based on the paracrine effects of several types of growth factors secreted by the stem cells. Patients with RD will benefit from the stem cell therapy.

CAS / MDL: 59865-13-3
研究领域: 眼科学 · 干细胞研究 · 神经科学 · 再生医学
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