Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imaging
Abstract Insights regarding the biodistribution and homing of mesenchymal stromal cells (MSCs), as well as their interaction with alloreactive T-cells are critical for understanding how MSCs can regulate graft-versus-host disease (GVHD) following allogeneic (allo) bone marrow transplantation (BMT)....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-28478-3 |
| _version_ | 1797864741975097344 |
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| author | Patiwet Wuttisarnwattana Saada Eid David L. Wilson Kenneth R. Cooke |
| author_facet | Patiwet Wuttisarnwattana Saada Eid David L. Wilson Kenneth R. Cooke |
| author_sort | Patiwet Wuttisarnwattana |
| collection | DOAJ |
| description | Abstract Insights regarding the biodistribution and homing of mesenchymal stromal cells (MSCs), as well as their interaction with alloreactive T-cells are critical for understanding how MSCs can regulate graft-versus-host disease (GVHD) following allogeneic (allo) bone marrow transplantation (BMT). We developed novel assays based on 3D, microscopic, cryo-imaging of whole-mouse-sized volumes to assess the therapeutic potential of human MSCs using an established mouse GVHD model. Following infusion, we quantitatively tracked fluorescently labeled, donor-derived, T-cells and third party MSCs in BMT recipients using multispectral cryo-imaging. Specific MSC homing sites were identified in the marginal zones in the spleen and the lymph nodes, where we believe MSC immunomodulation takes place. The number of MSCs found in spleen of the allo BMT recipients was about 200% more than that observed in the syngeneic group. To more carefully define the effects MSCs had on T cell activation and expansion, we developed novel T-cell proliferation assays including secondary lymphoid organ (SLO) enlargement and Carboxyfluoescein succinimidyl ester (CFSE) dilution. As anticipated, significant SLO volume enlargement and CFSE dilution was observed in allo but not syn BMT recipients due to rapid proliferation and expansion of labeled T-cells. MSC treatment markedly attenuated CFSE dilution and volume enlargement of SLO. These assays confirm evidence of potent, in vivo, immunomodulatory properties of MSC following allo BMT. Our innovative platform includes novel methods for tracking cells of interest as well as assessing therapeutic function of MSCs during GVHD induction. Our results support the use of MSCs treatment or prevention of GVHD and illuminate the wider adoption of MSCs as a standard medicinal cell therapy. |
| first_indexed | 2024-04-09T22:57:01Z |
| format | Article |
| id | doaj.art-2a8ece5d6dbb4aeaa2bcf1b970a13aed |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:57:01Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2a8ece5d6dbb4aeaa2bcf1b970a13aed2023-03-22T11:09:59ZengNature PortfolioScientific Reports2045-23222023-01-0113111310.1038/s41598-023-28478-3Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imagingPatiwet Wuttisarnwattana0Saada Eid1David L. Wilson2Kenneth R. Cooke3Optimization Theory and Applications for Engineering Systems Research Group, Department of Computer Engineering, Excellence Center in Infrastructure Technology and Transportation Engineering, Biomedical Engineering Institute, Chiang Mai UniversityDepartment of Pediatrics, Case Western Reserve UniversityDepartment of Biomedical Engineering, Case Western Reserve UniversityDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, Johns Hopkins UniversityAbstract Insights regarding the biodistribution and homing of mesenchymal stromal cells (MSCs), as well as their interaction with alloreactive T-cells are critical for understanding how MSCs can regulate graft-versus-host disease (GVHD) following allogeneic (allo) bone marrow transplantation (BMT). We developed novel assays based on 3D, microscopic, cryo-imaging of whole-mouse-sized volumes to assess the therapeutic potential of human MSCs using an established mouse GVHD model. Following infusion, we quantitatively tracked fluorescently labeled, donor-derived, T-cells and third party MSCs in BMT recipients using multispectral cryo-imaging. Specific MSC homing sites were identified in the marginal zones in the spleen and the lymph nodes, where we believe MSC immunomodulation takes place. The number of MSCs found in spleen of the allo BMT recipients was about 200% more than that observed in the syngeneic group. To more carefully define the effects MSCs had on T cell activation and expansion, we developed novel T-cell proliferation assays including secondary lymphoid organ (SLO) enlargement and Carboxyfluoescein succinimidyl ester (CFSE) dilution. As anticipated, significant SLO volume enlargement and CFSE dilution was observed in allo but not syn BMT recipients due to rapid proliferation and expansion of labeled T-cells. MSC treatment markedly attenuated CFSE dilution and volume enlargement of SLO. These assays confirm evidence of potent, in vivo, immunomodulatory properties of MSC following allo BMT. Our innovative platform includes novel methods for tracking cells of interest as well as assessing therapeutic function of MSCs during GVHD induction. Our results support the use of MSCs treatment or prevention of GVHD and illuminate the wider adoption of MSCs as a standard medicinal cell therapy.https://doi.org/10.1038/s41598-023-28478-3 |
| spellingShingle | Patiwet Wuttisarnwattana Saada Eid David L. Wilson Kenneth R. Cooke Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imaging Scientific Reports |
| title | Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imaging |
| title_full | Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imaging |
| title_fullStr | Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imaging |
| title_full_unstemmed | Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imaging |
| title_short | Assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft-versus-host disease using cryo-imaging |
| title_sort | assessment of the therapeutic role of mesenchymal stromal cells in a mouse model of graft versus host disease using cryo imaging |
| url | https://doi.org/10.1038/s41598-023-28478-3 |
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