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...
Main Authors: | , , , , , , , , , |
---|---|
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 |
_version_ | 1797388120476352512 |
---|---|
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. |
first_indexed | 2024-03-08T22:35:09Z |
format | Article |
id | doaj.art-3a9b2a2f8eca4935a435e775f297ee59 |
institution | Directory Open Access Journal |
issn | 1479-5876 |
language | English |
last_indexed | 2024-03-08T22:35:09Z |
publishDate | 2023-12-01 |
publisher | BMC |
record_format | Article |
series | Journal of Translational Medicine |
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 |
work_keys_str_mv | AT qianliu comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT junliu comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT minmeiguo comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT tzuchengsung comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT tingwang comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT taoyu comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT zeyutian comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT guopingfan comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT wencanwu comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel AT akonhiguchi comparisonofretinaldegenerationtreatmentwithfourtypesofdifferentmesenchymalstemcellshumaninducedpluripotentstemcellsandrpecellsinaratretinaldegenerationmodel |