Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function
Mesenchymal stromal cells (MSCs) represent a promising treatment for immune-related diseases due to their diverse immunomodulatory paracrine functions. However, progress of culture-expanded MSCs is hindered by inconsistent cell function, poor localization, and insufficient retention when administere...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/23/3738 |
| _version_ | 1797463488910589952 |
|---|---|
| author | Celia M. Dunn Sumako Kameishi Yun-Kyoung Cho Sun U. Song David W. Grainger Teruo Okano |
| author_facet | Celia M. Dunn Sumako Kameishi Yun-Kyoung Cho Sun U. Song David W. Grainger Teruo Okano |
| author_sort | Celia M. Dunn |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSCs) represent a promising treatment for immune-related diseases due to their diverse immunomodulatory paracrine functions. However, progress of culture-expanded MSCs is hindered by inconsistent cell function, poor localization, and insufficient retention when administered as suspended cell injections, thus placing spatiotemporal dosing constraints on therapeutic functions. To address these limitations, we introduce the combination of in vitro interferon-gamma (IFN-γ) priming, a key stimulator of MSC immunosuppressive potency, and thermoresponsive cultureware to harvest cultured MSCs as directly transplantable scaffold-free immunosuppressive cell sheets. Here, we demonstrate that MSC sheets produced with IFN-γ priming upregulate expression of immunosuppressive factors indoleamine 2,3-dioxygenase (IDO-1), interleukin-10 (IL-10), programmed death ligand-1 (PD-L1), and prostaglandin E2 (PGE2) in both dose- and duration-dependent manners. In addition, IFN-γ primed MSC sheets showed increased ability to inhibit T-cell proliferation via indirect and direct contact, specifically related to increased IDO-1 and PGE2 concentrations. Furthermore, this study’s use of human clinical-grade single-cell-derived clonal bone marrow-derived MSCs, contributes to the future translatability and clinical relevancy of the produced sheets. Ultimately, these results present the combination of IFN-γ priming and MSC sheets as a new strategy to improve MSC-mediated treatment of localized inflammatory diseases. |
| first_indexed | 2024-03-09T17:51:27Z |
| format | Article |
| id | doaj.art-818d1d4f5a4548eebaa9b2deb824f79b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:27Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-818d1d4f5a4548eebaa9b2deb824f79b2023-11-24T10:43:01ZengMDPI AGCells2073-44092022-11-011123373810.3390/cells11233738Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive FunctionCelia M. Dunn0Sumako Kameishi1Yun-Kyoung Cho2Sun U. Song3David W. Grainger4Teruo Okano5Cell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USACell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USASCM Lifescience Co., Ltd., Incheon 21999, Republic of KoreaSCM Lifescience Co., Ltd., Incheon 21999, Republic of KoreaCell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USACell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USAMesenchymal stromal cells (MSCs) represent a promising treatment for immune-related diseases due to their diverse immunomodulatory paracrine functions. However, progress of culture-expanded MSCs is hindered by inconsistent cell function, poor localization, and insufficient retention when administered as suspended cell injections, thus placing spatiotemporal dosing constraints on therapeutic functions. To address these limitations, we introduce the combination of in vitro interferon-gamma (IFN-γ) priming, a key stimulator of MSC immunosuppressive potency, and thermoresponsive cultureware to harvest cultured MSCs as directly transplantable scaffold-free immunosuppressive cell sheets. Here, we demonstrate that MSC sheets produced with IFN-γ priming upregulate expression of immunosuppressive factors indoleamine 2,3-dioxygenase (IDO-1), interleukin-10 (IL-10), programmed death ligand-1 (PD-L1), and prostaglandin E2 (PGE2) in both dose- and duration-dependent manners. In addition, IFN-γ primed MSC sheets showed increased ability to inhibit T-cell proliferation via indirect and direct contact, specifically related to increased IDO-1 and PGE2 concentrations. Furthermore, this study’s use of human clinical-grade single-cell-derived clonal bone marrow-derived MSCs, contributes to the future translatability and clinical relevancy of the produced sheets. Ultimately, these results present the combination of IFN-γ priming and MSC sheets as a new strategy to improve MSC-mediated treatment of localized inflammatory diseases.https://www.mdpi.com/2073-4409/11/23/3738mesenchymal stem cellsimmunomodulationpre-conditioninglicensingtissue engineeringcellular therapy |
| spellingShingle | Celia M. Dunn Sumako Kameishi Yun-Kyoung Cho Sun U. Song David W. Grainger Teruo Okano Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function Cells mesenchymal stem cells immunomodulation pre-conditioning licensing tissue engineering cellular therapy |
| title | Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function |
| title_full | Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function |
| title_fullStr | Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function |
| title_full_unstemmed | Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function |
| title_short | Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function |
| title_sort | interferon gamma primed human clonal mesenchymal stromal cell sheets exhibit enhanced immunosuppressive function |
| topic | mesenchymal stem cells immunomodulation pre-conditioning licensing tissue engineering cellular therapy |
| url | https://www.mdpi.com/2073-4409/11/23/3738 |
| work_keys_str_mv | AT celiamdunn interferongammaprimedhumanclonalmesenchymalstromalcellsheetsexhibitenhancedimmunosuppressivefunction AT sumakokameishi interferongammaprimedhumanclonalmesenchymalstromalcellsheetsexhibitenhancedimmunosuppressivefunction AT yunkyoungcho interferongammaprimedhumanclonalmesenchymalstromalcellsheetsexhibitenhancedimmunosuppressivefunction AT sunusong interferongammaprimedhumanclonalmesenchymalstromalcellsheetsexhibitenhancedimmunosuppressivefunction AT davidwgrainger interferongammaprimedhumanclonalmesenchymalstromalcellsheetsexhibitenhancedimmunosuppressivefunction AT teruookano interferongammaprimedhumanclonalmesenchymalstromalcellsheetsexhibitenhancedimmunosuppressivefunction |