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

Abstract 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 sub...

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Main Authors: Qian Liu, Jun Liu, Minmei Guo, Tzu-Cheng Sung, Ting Wang, Tao Yu, Zeyu Tian, Guoping Fan, Wencan Wu, Akon Higuchi
Format: Article
Language:English
Published: BMC 2023-12-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-023-04785-1
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author Qian Liu
Jun Liu
Minmei Guo
Tzu-Cheng Sung
Ting Wang
Tao Yu
Zeyu Tian
Guoping Fan
Wencan Wu
Akon Higuchi
author_facet Qian Liu
Jun Liu
Minmei Guo
Tzu-Cheng Sung
Ting Wang
Tao Yu
Zeyu Tian
Guoping Fan
Wencan Wu
Akon Higuchi
author_sort Qian Liu
collection DOAJ
description Abstract 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. Conclusions Compared 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.
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spelling doaj.art-3a9b2a2f8eca4935a435e775f297ee592023-12-17T12:28:34ZengBMCJournal of Translational Medicine1479-58762023-12-0121112210.1186/s12967-023-04785-1Comparison 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 modelQian Liu0Jun Liu1Minmei Guo2Tzu-Cheng Sung3Ting Wang4Tao Yu5Zeyu Tian6Guoping Fan7Wencan Wu8Akon Higuchi9State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityDepartment of Human Genetics, David Geffen School of Medicine, UCLAState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityAbstract 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. Conclusions Compared 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.https://doi.org/10.1186/s12967-023-04785-1Retinal degenerationStem cell therapyRetinal pigmented epitheliumRoyal College of Surgeons ratsHuman pluripotent stem cellMesenchymal stem cell
spellingShingle Qian Liu
Jun Liu
Minmei Guo
Tzu-Cheng Sung
Ting Wang
Tao Yu
Zeyu Tian
Guoping Fan
Wencan Wu
Akon Higuchi
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
Journal of Translational Medicine
Retinal degeneration
Stem cell therapy
Retinal pigmented epithelium
Royal College of Surgeons rats
Human pluripotent stem cell
Mesenchymal stem cell
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Retinal degeneration
Stem cell therapy
Retinal pigmented epithelium
Royal College of Surgeons rats
Human pluripotent stem cell
Mesenchymal stem cell
url https://doi.org/10.1186/s12967-023-04785-1
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