Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease
The immune-mediated tissue destruction of graft-vs-host disease (GvHD) remains a major barrier to greater use of hematopoietic stem cell transplantation (HSCT). Mesenchymal stem cells (MSCs) have intrinsic immunosuppressive qualities and are being actively investigated as a therapeutic strategy for...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-03-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506119300315 |
| _version_ | 1818620145222811648 |
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| author | E. Ilker Ozay Jyothi Vijayaraghavan Gabriela Gonzalez-Perez Sudarvili Shanthalingam Heather L. Sherman Daniel T. Garrigan, Jr. Karthik Chandiran Joe A. Torres Barbara A. Osborne Gregory N. Tew Igor I. Slukvin Ross A. Macdonald Kilian Kelly Lisa M. Minter |
| author_facet | E. Ilker Ozay Jyothi Vijayaraghavan Gabriela Gonzalez-Perez Sudarvili Shanthalingam Heather L. Sherman Daniel T. Garrigan, Jr. Karthik Chandiran Joe A. Torres Barbara A. Osborne Gregory N. Tew Igor I. Slukvin Ross A. Macdonald Kilian Kelly Lisa M. Minter |
| author_sort | E. Ilker Ozay |
| collection | DOAJ |
| description | The immune-mediated tissue destruction of graft-vs-host disease (GvHD) remains a major barrier to greater use of hematopoietic stem cell transplantation (HSCT). Mesenchymal stem cells (MSCs) have intrinsic immunosuppressive qualities and are being actively investigated as a therapeutic strategy for treating GvHD. We characterized Cymerus™ MSCs, which are derived from adult, induced pluripotent stem cells (iPSCs), and show they display surface markers and tri-lineage differentiation consistent with MSCs isolated from bone marrow (BM). Administering iPSC-MSCs altered phosphorylation and cellular localization of the T cell-specific kinase, Protein Kinase C theta (PKCθ), attenuated disease severity, and prolonged survival in a humanized mouse model of GvHD. Finally, we evaluated a constellation of pro-inflammatory molecules on circulating PBMCs that correlated closely with disease progression and which may serve as biomarkers to monitor therapeutic response. Altogether, our data suggest Cymerus iPSC-MSCs offer the potential for an off-the-shelf, cell-based therapy to treat GvHD. Keywords: PKCθ, Graft-vs-host disease, Mesenchymal stem cell, Induced pluripotent stem cell, Humanized mouse model |
| first_indexed | 2024-12-16T17:48:43Z |
| format | Article |
| id | doaj.art-a4c225c8c2c14d8b9f7ff56e9a4ae1d6 |
| institution | Directory Open Access Journal |
| issn | 1873-5061 |
| language | English |
| last_indexed | 2024-12-16T17:48:43Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-a4c225c8c2c14d8b9f7ff56e9a4ae1d62022-12-21T22:22:23ZengElsevierStem Cell Research1873-50612019-03-0135Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host diseaseE. Ilker Ozay0Jyothi Vijayaraghavan1Gabriela Gonzalez-Perez2Sudarvili Shanthalingam3Heather L. Sherman4Daniel T. Garrigan, Jr.5Karthik Chandiran6Joe A. Torres7Barbara A. Osborne8Gregory N. Tew9Igor I. Slukvin10Ross A. Macdonald11Kilian Kelly12Lisa M. Minter13Graduate Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, United States; Department of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United States; Department of Polymer Science & Engineering, University of Massachusetts Amherst, Amherst, MA 01003, United StatesDepartment of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesDepartment of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesDepartment of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesGraduate Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, United States; Department of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesDepartment of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesGraduate Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, United States; Department of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesGraduate Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, United States; Department of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesGraduate Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, United States; Department of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United StatesDepartment of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United StatesCynata Therapeutics Limited, Carlton, Victoria 3053, Australia; Department of Polymer Science & Engineering, University of Massachusetts Amherst, Amherst, MA 01003, United StatesDepartment of Polymer Science & Engineering, University of Massachusetts Amherst, Amherst, MA 01003, United StatesDepartment of Polymer Science & Engineering, University of Massachusetts Amherst, Amherst, MA 01003, United StatesGraduate Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, United States; Department of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United States; Corresponding author at: Department of Veterinary & Animal Sciences, 427K Integrated Sciences Building, 661 North Pleasant Street, University of Massachusetts Amherst, Amherst, MA 01003, United States.The immune-mediated tissue destruction of graft-vs-host disease (GvHD) remains a major barrier to greater use of hematopoietic stem cell transplantation (HSCT). Mesenchymal stem cells (MSCs) have intrinsic immunosuppressive qualities and are being actively investigated as a therapeutic strategy for treating GvHD. We characterized Cymerus™ MSCs, which are derived from adult, induced pluripotent stem cells (iPSCs), and show they display surface markers and tri-lineage differentiation consistent with MSCs isolated from bone marrow (BM). Administering iPSC-MSCs altered phosphorylation and cellular localization of the T cell-specific kinase, Protein Kinase C theta (PKCθ), attenuated disease severity, and prolonged survival in a humanized mouse model of GvHD. Finally, we evaluated a constellation of pro-inflammatory molecules on circulating PBMCs that correlated closely with disease progression and which may serve as biomarkers to monitor therapeutic response. Altogether, our data suggest Cymerus iPSC-MSCs offer the potential for an off-the-shelf, cell-based therapy to treat GvHD. Keywords: PKCθ, Graft-vs-host disease, Mesenchymal stem cell, Induced pluripotent stem cell, Humanized mouse modelhttp://www.sciencedirect.com/science/article/pii/S1873506119300315 |
| spellingShingle | E. Ilker Ozay Jyothi Vijayaraghavan Gabriela Gonzalez-Perez Sudarvili Shanthalingam Heather L. Sherman Daniel T. Garrigan, Jr. Karthik Chandiran Joe A. Torres Barbara A. Osborne Gregory N. Tew Igor I. Slukvin Ross A. Macdonald Kilian Kelly Lisa M. Minter Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease Stem Cell Research |
| title | Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease |
| title_full | Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease |
| title_fullStr | Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease |
| title_full_unstemmed | Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease |
| title_short | Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease |
| title_sort | cymerus™ ipsc mscs significantly prolong survival in a pre clinical humanized mouse model of graft vs host disease |
| url | http://www.sciencedirect.com/science/article/pii/S1873506119300315 |
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