Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress
Oxidative stress leads to the degeneration of retinal pigment epithelial (RPE) and photoreceptor cells. We evaluated the potential of adipose-derived mesenchymal stem cells (ASCs) as a therapeutic tool by studying the migration capacity of ASCs in vitro and their protective effect against RPE cell d...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/9682856 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832568360160722944 |
|---|---|
| author | Aya Barzelay Shira Weisthal Algor Anat Niztan Sebastian Katz Moshe Benhamou Itay Nakdimon Noam Azmon Sandy Gozlan Daphna Mezad-Koursh Meira Neudorfer Michaella Goldstein Benjamin Meilik Anat Loewenstein Adiel Barak |
| author_facet | Aya Barzelay Shira Weisthal Algor Anat Niztan Sebastian Katz Moshe Benhamou Itay Nakdimon Noam Azmon Sandy Gozlan Daphna Mezad-Koursh Meira Neudorfer Michaella Goldstein Benjamin Meilik Anat Loewenstein Adiel Barak |
| author_sort | Aya Barzelay |
| collection | DOAJ |
| description | Oxidative stress leads to the degeneration of retinal pigment epithelial (RPE) and photoreceptor cells. We evaluated the potential of adipose-derived mesenchymal stem cells (ASCs) as a therapeutic tool by studying the migration capacity of ASCs in vitro and their protective effect against RPE cell death under oxidative stress in vitro and in vivo. ASCs exhibited enhanced migration when exposed to conditioned medium of oxidative stressed RPE cells obtained by hydrogen peroxide. Migration-related axis SDF-1/CXCR4 was studied, and upregulation of SDF-1 in stressed RPE and of CXCR4 in ASCs was detected. Moreover, ASCs’ conditioned medium prevented H2O2-induced cell death of RPE cells. Early passage ASCs had high expression level of HGF, low VEGF levels, and unmodulated IL-1β levels, compared to late passage ASCs. Thus, early passage ASCs show the potential to migrate towards damaged RPE cells and protect them in a paracrine manner from cell death induced by oxidative stress. In vivo, mice received systemic injection of NaIO3, and 72 h later, ASCs were transplanted in the subretinal space. Seven days after ASC transplantation, the eyes were enucleated fixed and frozen for immunohistochemical analysis. Under such conditions, ASC-treated mice showed preservation of nuclear layers in the outer nuclear layer and stronger staining of RPE and photoreceptor layer, compared to PBS-treated mice. Taken together, our results indicate that ASCs are able to home in on damaged RPE cells and protect against damage to the RPE and PR layers caused by oxidative stress. These data imply the potential that ASCs have in regenerating RPE under oxidative stress, providing the basis for a therapeutic approach to retinal degeneration diseases related to oxidative stress that could help save the eyesight of millions of people worldwide. |
| format | Article |
| id | doaj-art-5e93dd85401b4290929c3bb39a1a050d |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-5e93dd85401b4290929c3bb39a1a050d2025-02-03T00:59:16ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/96828569682856Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative StressAya Barzelay0Shira Weisthal Algor1Anat Niztan2Sebastian Katz3Moshe Benhamou4Itay Nakdimon5Noam Azmon6Sandy Gozlan7Daphna Mezad-Koursh8Meira Neudorfer9Michaella Goldstein10Benjamin Meilik11Anat Loewenstein12Adiel Barak13Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelOxidative stress leads to the degeneration of retinal pigment epithelial (RPE) and photoreceptor cells. We evaluated the potential of adipose-derived mesenchymal stem cells (ASCs) as a therapeutic tool by studying the migration capacity of ASCs in vitro and their protective effect against RPE cell death under oxidative stress in vitro and in vivo. ASCs exhibited enhanced migration when exposed to conditioned medium of oxidative stressed RPE cells obtained by hydrogen peroxide. Migration-related axis SDF-1/CXCR4 was studied, and upregulation of SDF-1 in stressed RPE and of CXCR4 in ASCs was detected. Moreover, ASCs’ conditioned medium prevented H2O2-induced cell death of RPE cells. Early passage ASCs had high expression level of HGF, low VEGF levels, and unmodulated IL-1β levels, compared to late passage ASCs. Thus, early passage ASCs show the potential to migrate towards damaged RPE cells and protect them in a paracrine manner from cell death induced by oxidative stress. In vivo, mice received systemic injection of NaIO3, and 72 h later, ASCs were transplanted in the subretinal space. Seven days after ASC transplantation, the eyes were enucleated fixed and frozen for immunohistochemical analysis. Under such conditions, ASC-treated mice showed preservation of nuclear layers in the outer nuclear layer and stronger staining of RPE and photoreceptor layer, compared to PBS-treated mice. Taken together, our results indicate that ASCs are able to home in on damaged RPE cells and protect against damage to the RPE and PR layers caused by oxidative stress. These data imply the potential that ASCs have in regenerating RPE under oxidative stress, providing the basis for a therapeutic approach to retinal degeneration diseases related to oxidative stress that could help save the eyesight of millions of people worldwide.http://dx.doi.org/10.1155/2018/9682856 |
| spellingShingle | Aya Barzelay Shira Weisthal Algor Anat Niztan Sebastian Katz Moshe Benhamou Itay Nakdimon Noam Azmon Sandy Gozlan Daphna Mezad-Koursh Meira Neudorfer Michaella Goldstein Benjamin Meilik Anat Loewenstein Adiel Barak Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress Stem Cells International |
| title | Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress |
| title_full | Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress |
| title_fullStr | Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress |
| title_full_unstemmed | Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress |
| title_short | Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress |
| title_sort | adipose derived mesenchymal stem cells migrate and rescue rpe in the setting of oxidative stress |
| url | http://dx.doi.org/10.1155/2018/9682856 |
| work_keys_str_mv | AT ayabarzelay adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT shiraweisthalalgor adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT anatniztan adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT sebastiankatz adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT moshebenhamou adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT itaynakdimon adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT noamazmon adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT sandygozlan adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT daphnamezadkoursh adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT meiraneudorfer adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT michaellagoldstein adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT benjaminmeilik adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT anatloewenstein adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress AT adielbarak adiposederivedmesenchymalstemcellsmigrateandrescuerpeinthesettingofoxidativestress |