PS7:130 Interferon beta blockade rescues human bm-msc osteoblastogenesis defects in systemic lupus erythematosus
| Autor: | R J Looney, Lin Gao, Jennifer H. Anolik |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
business.industry Mesenchymal stem cell Lupus nephritis CD34 Endoglin medicine.disease Transplantation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure immune system diseases Immunology medicine CD90 Bone marrow Stem cell skin and connective tissue diseases business 030217 neurology & neurosurgery |
| Zdroj: | Poster session 7: New drugs and trageted therapy. |
| DOI: | 10.1136/lupus-2018-abstract.173 |
| Popis: | Bone marrow mesenchymal stromal cells (BM-MSCs) are multipotent stem cells that can differentiate into chondrocytes, osteoblasts and adipocytes. SLE has been implicated as a stem cell disorder with impaired immunomodulatory function of SLE BM-MSCs and improvement of lupus nephritis with healthy MSCs transplantation has been suggested. However, the exact differentiation defects of SLE BM-MSCs have not been addressed, nor and potential interventions studied. Our previous work indicates upregulation of IFN beta specific genes in human SLE bone marrow derived MSCs compared to normal bone marrow MSC. Here we set out to investigate the differentiation defects of SLE BM-MSCs and potential intervention approaches. We compared 6 age paired BM aspirates from healthy controls and SLE patients. BM-MSCs from SLE patients and healthy controls were isolated and cultured. The MSC surface markers are positive for CD73, CD90 and CD105, but negative for CD34 and CD45 in both healthy and SLE BM-MSCs after culture. No difference was observed in the surface markers between SLE and healthy BM-MSCs. However, SLE MSCs display significantly reduced osteoblastogenesis markers, such ALP (6 fold, p IFN-I signature is an important feature of SLE. Our present work suggests that SLE BM-MSCs produce IFN beta, mediating a decrease in osteoblastogenesis capacity. The successful rescue of the SLE BM-MSCs osteoblastogenesis defect with an IFN beta neutralising antibody highlights IFN as a new potential therapeutic target for SLE treatment. |
| Databáze: | OpenAIRE |
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