Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients
BackgroundSystemic administration of marrow stromal cells (MSCs) leads to the release of a broad range of factors mediating recovery in rodent stroke models. The release of these factors could depend on the various cell types within the peripheral blood as they contact systemically administered MSCs...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.958579/full |
| _version_ | 1811243063095328768 |
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| author | Nikunj Satani Kaushik Parsha Courtney Davis Adrian Gee Scott D. Olson Jaroslaw Aronowski Sean I. Savitz |
| author_facet | Nikunj Satani Kaushik Parsha Courtney Davis Adrian Gee Scott D. Olson Jaroslaw Aronowski Sean I. Savitz |
| author_sort | Nikunj Satani |
| collection | DOAJ |
| description | BackgroundSystemic administration of marrow stromal cells (MSCs) leads to the release of a broad range of factors mediating recovery in rodent stroke models. The release of these factors could depend on the various cell types within the peripheral blood as they contact systemically administered MSCs. In this study, we assessed the immunomodulatory interactions of MSCs with peripheral blood derived monocytes (Mϕ) collected from acute stroke patients.MethodsPeripheral blood from stroke patients was collected at 5–7 days (N = 5) after symptom onset and from age-matched healthy controls (N = 5) using mononuclear cell preparation (CPT) tubes. After processing, plasma and other cellular fractions were removed, and Mϕ were isolated from the mononuclear fraction using CD14 microbeads. Mϕ were then either cultured alone or co-cultured with MSCs in a trans-well cell-culture system. Secretomes were analyzed after 24 h of co-cultures using a MAGPIX reader.ResultsOur results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5–7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared to the secretions from monocytes alone. When MSCs were added to monocytes from stroke patients, they decreased the levels of IL-1β, and increased the levels of IL-10 significantly more as compared to when they were added to monocytes from control patients.ConclusionThe systemic circulation of stroke patients may differentially interact with MSCs to release soluble factors integral to their paracrine mechanisms of benefit. Our study finds that the effect of MSCs on Mϕ is different on those derived from stroke patients blood as compared to healthy controls. These findings suggest immunomodulation of peripheral immune cells as a therapeutic target for MSCs in patients with acute stroke. |
| first_indexed | 2024-04-12T14:00:39Z |
| format | Article |
| id | doaj.art-4f0c766a1d884f41a21d5af94ad16da2 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-12T14:00:39Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-4f0c766a1d884f41a21d5af94ad16da22022-12-22T03:30:12ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-10-011310.3389/fneur.2022.958579958579Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patientsNikunj Satani0Kaushik Parsha1Courtney Davis2Adrian Gee3Scott D. Olson4Jaroslaw Aronowski5Sean I. Savitz6Department of Neurology, McGovern Medical School, Institute for Stroke and Cerebrovascular Diseases, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, Institute for Stroke and Cerebrovascular Diseases, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, Institute for Stroke and Cerebrovascular Diseases, The University of Texas Health Science Center at Houston, Houston, TX, United StatesCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pediatric Surgery, McGovern Medical School at UTHealth, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, Institute for Stroke and Cerebrovascular Diseases, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, Institute for Stroke and Cerebrovascular Diseases, The University of Texas Health Science Center at Houston, Houston, TX, United StatesBackgroundSystemic administration of marrow stromal cells (MSCs) leads to the release of a broad range of factors mediating recovery in rodent stroke models. The release of these factors could depend on the various cell types within the peripheral blood as they contact systemically administered MSCs. In this study, we assessed the immunomodulatory interactions of MSCs with peripheral blood derived monocytes (Mϕ) collected from acute stroke patients.MethodsPeripheral blood from stroke patients was collected at 5–7 days (N = 5) after symptom onset and from age-matched healthy controls (N = 5) using mononuclear cell preparation (CPT) tubes. After processing, plasma and other cellular fractions were removed, and Mϕ were isolated from the mononuclear fraction using CD14 microbeads. Mϕ were then either cultured alone or co-cultured with MSCs in a trans-well cell-culture system. Secretomes were analyzed after 24 h of co-cultures using a MAGPIX reader.ResultsOur results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5–7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared to the secretions from monocytes alone. When MSCs were added to monocytes from stroke patients, they decreased the levels of IL-1β, and increased the levels of IL-10 significantly more as compared to when they were added to monocytes from control patients.ConclusionThe systemic circulation of stroke patients may differentially interact with MSCs to release soluble factors integral to their paracrine mechanisms of benefit. Our study finds that the effect of MSCs on Mϕ is different on those derived from stroke patients blood as compared to healthy controls. These findings suggest immunomodulation of peripheral immune cells as a therapeutic target for MSCs in patients with acute stroke.https://www.frontiersin.org/articles/10.3389/fneur.2022.958579/fullmonocytesmesenchymal stromal cells (MSCs)stromal cellsstrokesecretome |
| spellingShingle | Nikunj Satani Kaushik Parsha Courtney Davis Adrian Gee Scott D. Olson Jaroslaw Aronowski Sean I. Savitz Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients Frontiers in Neurology monocytes mesenchymal stromal cells (MSCs) stromal cells stroke secretome |
| title | Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients |
| title_full | Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients |
| title_fullStr | Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients |
| title_full_unstemmed | Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients |
| title_short | Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients |
| title_sort | peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients |
| topic | monocytes mesenchymal stromal cells (MSCs) stromal cells stroke secretome |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.958579/full |
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