Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety
Mesenchymal stromal cells (MSCs) are used as salvage therapy to treat steroid-refractory acute graft-versus-host disease (aGvHD). We studied the immunological response to MSC treatment in 16 aGvHD patients by assessing lymphocyte profiles and three proposed aGvHD serum markers during the MSC treatme...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050118300135 |
| _version_ | 1818241885758554112 |
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| author | Joni Keto Tanja Kaartinen Urpu Salmenniemi Johanna Castrén Jukka Partanen Arno Hänninen Matti Korhonen Kaarina Lähteenmäki Maija Itälä-Remes Johanna Nystedt |
| author_facet | Joni Keto Tanja Kaartinen Urpu Salmenniemi Johanna Castrén Jukka Partanen Arno Hänninen Matti Korhonen Kaarina Lähteenmäki Maija Itälä-Remes Johanna Nystedt |
| author_sort | Joni Keto |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSCs) are used as salvage therapy to treat steroid-refractory acute graft-versus-host disease (aGvHD). We studied the immunological response to MSC treatment in 16 aGvHD patients by assessing lymphocyte profiles and three proposed aGvHD serum markers during the MSC treatment. Surprisingly, there were no obvious differences in the lymphocyte profiles between the responders and non-responders. The numbers of T, B, and NK cells were below the normal reference interval in all patients. CD4+ T helper (Th) cell levels remained particularly low throughout the follow-up period. The relative proportion of Th1 cells decreased, while regulatory T cells remained unaltered, and only very few Th2 and Th17 cells could be detected. Serum concentrations of regenerating islet-derived protein 3-alpha, cytokeratin-18 fragments (CK18F), and elafin were significantly elevated in patient samples compared with healthy controls, but only CK18F showed any potential in the prediction of patients’ response to MSCs. No obvious markers for MSC therapy response were revealed in this study, but the results suggest that allogeneic MSCs do not provoke overt T cell-mediated immune responses at least in immunosuppressed aGvHD patients. The results advocate for the safety of MSC therapy and bring new insights in MSC immunomodulation mechanisms. Keywords: allogeneic hematopoietic stem cell transplantation, biomarker, graft-versus-host disease, mesenchymal stromal cells, T cell, safety |
| first_indexed | 2024-12-12T13:36:27Z |
| format | Article |
| id | doaj.art-10f41fb7114346d583caa5327b369bf7 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-12T13:36:27Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-10f41fb7114346d583caa5327b369bf72022-12-22T00:22:56ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012018-06-019109118Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment SafetyJoni Keto0Tanja Kaartinen1Urpu Salmenniemi2Johanna Castrén3Jukka Partanen4Arno Hänninen5Matti Korhonen6Kaarina Lähteenmäki7Maija Itälä-Remes8Johanna Nystedt9Finnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, FinlandFinnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, FinlandDivision of Medicine, Department of Hematology and Stem Cell Transplantation Unit, Turku University Hospital, Hämeentie 11, FI-20521 Turku, FinlandFinnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, FinlandFinnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, FinlandDepartment of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, FI-20520 Turku, FinlandFinnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, FinlandFinnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, FinlandDivision of Medicine, Department of Hematology and Stem Cell Transplantation Unit, Turku University Hospital, Hämeentie 11, FI-20521 Turku, FinlandFinnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, Finland; Corresponding author: Johanna Nystedt, PhD, Adjunct Professor, Finnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, Finland.Mesenchymal stromal cells (MSCs) are used as salvage therapy to treat steroid-refractory acute graft-versus-host disease (aGvHD). We studied the immunological response to MSC treatment in 16 aGvHD patients by assessing lymphocyte profiles and three proposed aGvHD serum markers during the MSC treatment. Surprisingly, there were no obvious differences in the lymphocyte profiles between the responders and non-responders. The numbers of T, B, and NK cells were below the normal reference interval in all patients. CD4+ T helper (Th) cell levels remained particularly low throughout the follow-up period. The relative proportion of Th1 cells decreased, while regulatory T cells remained unaltered, and only very few Th2 and Th17 cells could be detected. Serum concentrations of regenerating islet-derived protein 3-alpha, cytokeratin-18 fragments (CK18F), and elafin were significantly elevated in patient samples compared with healthy controls, but only CK18F showed any potential in the prediction of patients’ response to MSCs. No obvious markers for MSC therapy response were revealed in this study, but the results suggest that allogeneic MSCs do not provoke overt T cell-mediated immune responses at least in immunosuppressed aGvHD patients. The results advocate for the safety of MSC therapy and bring new insights in MSC immunomodulation mechanisms. Keywords: allogeneic hematopoietic stem cell transplantation, biomarker, graft-versus-host disease, mesenchymal stromal cells, T cell, safetyhttp://www.sciencedirect.com/science/article/pii/S2329050118300135 |
| spellingShingle | Joni Keto Tanja Kaartinen Urpu Salmenniemi Johanna Castrén Jukka Partanen Arno Hänninen Matti Korhonen Kaarina Lähteenmäki Maija Itälä-Remes Johanna Nystedt Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety Molecular Therapy: Methods & Clinical Development |
| title | Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety |
| title_full | Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety |
| title_fullStr | Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety |
| title_full_unstemmed | Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety |
| title_short | Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety |
| title_sort | immunomonitoring of msc treated gvhd patients reveals only moderate potential for response prediction but indicates treatment safety |
| url | http://www.sciencedirect.com/science/article/pii/S2329050118300135 |
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