Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling
Bone marrow mesenchymal stem cells (BM MSCs) play a tumor-supportive role in promoting drug resistance and disease relapse in multiple myeloma (MM). Recent studies have discovered a sub-population of MSCs, known as inflammatory MSCs (iMSCs), exclusive to the MM BM microenvironment and implicated in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/21/5148 |
| _version_ | 1797632110541930496 |
|---|---|
| author | Lei Wang Weijun Yi Li Ma Emily Lecea Lori A. Hazlehurst Donald A. Adjeroh Gangqing Hu |
| author_facet | Lei Wang Weijun Yi Li Ma Emily Lecea Lori A. Hazlehurst Donald A. Adjeroh Gangqing Hu |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | Bone marrow mesenchymal stem cells (BM MSCs) play a tumor-supportive role in promoting drug resistance and disease relapse in multiple myeloma (MM). Recent studies have discovered a sub-population of MSCs, known as inflammatory MSCs (iMSCs), exclusive to the MM BM microenvironment and implicated in drug resistance. Through a sophisticated analysis of public expression data from unexpanded BM MSCs, we uncovered a positive association between iMSC signature expression and minimal residual disease. While in vitro expansion generally results in the loss of the iMSC signature, our meta-analysis of additional public expression data demonstrated that cytokine stimulation, including IL1-β and TNF-α, as well as immune cells such as neutrophils, macrophages, and MM cells, can reactivate the signature expression of iMSCs to varying extents. These findings underscore the importance and potential utility of cytokine stimulation in mimicking the gene expression signature of early passage of iMSCs for functional characterizations of their tumor-supportive roles in MM. |
| first_indexed | 2024-03-11T11:32:15Z |
| format | Article |
| id | doaj.art-00d45c80262f4742b5910fdec1a9ea2c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T11:32:15Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-00d45c80262f4742b5910fdec1a9ea2c2023-11-10T15:00:02ZengMDPI AGCancers2072-66942023-10-011521514810.3390/cancers15215148Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro ModelingLei Wang0Weijun Yi1Li Ma2Emily Lecea3Lori A. Hazlehurst4Donald A. Adjeroh5Gangqing Hu6Department of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, WV 26505, USADepartment of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, WV 26505, USADepartment of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, WV 26505, USADepartment of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, WV 26505, USAWVU Cancer Institute, West Virginia University, Morgantown, WV 26506, USALane Department of Computer Science & Electrical Engineering, West Virginia University, Morgantown, WV 26506, USADepartment of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, WV 26505, USABone marrow mesenchymal stem cells (BM MSCs) play a tumor-supportive role in promoting drug resistance and disease relapse in multiple myeloma (MM). Recent studies have discovered a sub-population of MSCs, known as inflammatory MSCs (iMSCs), exclusive to the MM BM microenvironment and implicated in drug resistance. Through a sophisticated analysis of public expression data from unexpanded BM MSCs, we uncovered a positive association between iMSC signature expression and minimal residual disease. While in vitro expansion generally results in the loss of the iMSC signature, our meta-analysis of additional public expression data demonstrated that cytokine stimulation, including IL1-β and TNF-α, as well as immune cells such as neutrophils, macrophages, and MM cells, can reactivate the signature expression of iMSCs to varying extents. These findings underscore the importance and potential utility of cytokine stimulation in mimicking the gene expression signature of early passage of iMSCs for functional characterizations of their tumor-supportive roles in MM.https://www.mdpi.com/2072-6694/15/21/5148multiple myelomabone marrowinflammatory MSCstranscriptional signatureIL-1β |
| spellingShingle | Lei Wang Weijun Yi Li Ma Emily Lecea Lori A. Hazlehurst Donald A. Adjeroh Gangqing Hu Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling Cancers multiple myeloma bone marrow inflammatory MSCs transcriptional signature IL-1β |
| title | Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling |
| title_full | Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling |
| title_fullStr | Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling |
| title_full_unstemmed | Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling |
| title_short | Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling |
| title_sort | inflammatory bone marrow mesenchymal stem cells in multiple myeloma transcriptional signature and in vitro modeling |
| topic | multiple myeloma bone marrow inflammatory MSCs transcriptional signature IL-1β |
| url | https://www.mdpi.com/2072-6694/15/21/5148 |
| work_keys_str_mv | AT leiwang inflammatorybonemarrowmesenchymalstemcellsinmultiplemyelomatranscriptionalsignatureandinvitromodeling AT weijunyi inflammatorybonemarrowmesenchymalstemcellsinmultiplemyelomatranscriptionalsignatureandinvitromodeling AT lima inflammatorybonemarrowmesenchymalstemcellsinmultiplemyelomatranscriptionalsignatureandinvitromodeling AT emilylecea inflammatorybonemarrowmesenchymalstemcellsinmultiplemyelomatranscriptionalsignatureandinvitromodeling AT loriahazlehurst inflammatorybonemarrowmesenchymalstemcellsinmultiplemyelomatranscriptionalsignatureandinvitromodeling AT donaldaadjeroh inflammatorybonemarrowmesenchymalstemcellsinmultiplemyelomatranscriptionalsignatureandinvitromodeling AT gangqinghu inflammatorybonemarrowmesenchymalstemcellsinmultiplemyelomatranscriptionalsignatureandinvitromodeling |