Compromised Antibacterial Function of Multipotent Stromal Cells in Diabetes.
Citation: Stem Cells & Development. 28(4):268-277, 2019 02 15.PMID: 30572796Institution: MedStar Union Memorial HospitalDepartment: Orthobiologic Laboratory | Orthopaedic SurgeryForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Antimicrobial Cationic Peptides/me [Metabolism] | *Cytokines/me [Metabolism] | *Diabetes Mellitus/im [Immunology] | *Phagocytosis | *Pluripotent Stem Cells/im [Immunology] | Aged | Antimicrobial Cationic Peptides/ge [Genetics] | Bone Marrow Cells/im [Immunology] | Cells, Cultured | Chemokine CCL2/ge [Genetics] | Chemokine CCL2/me [Metabolism] | Cytokines/ge [Genetics] | Escherichia coli/de [Drug Effects] | Female | Humans | Indoleamine-Pyrrole 2,3,-Dioxygenase/ge [Genetics] | Indoleamine-Pyrrole 2,3,-Dioxygenase/me [Metabolism] | Macrophages/im [Immunology] | Male | Middle AgedYear: 2019ISSN:- 1547-3287
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
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Journal Article | MedStar Authors Catalog | Article | 30572796 | Available | 30572796 |
In diabetes, multipotent stromal cells (MSCs) are functionally deficient. It is unknown, however, whether their antibacterial function is compromised. In this study, MSCs were isolated from the bone marrow samples provided by 9 diabetic and 6 non-diabetic donors and treated with or without E. coli lipopolysaccharides (LPS). The supernatant of diabetic MSCs (MSCs-dia) and non-diabetic control MSCs (MSCs-c) was added into the cultures of E. coli for evaluation of the effect of MSCs-dia and MSCs-c on bacterial growth. The number of E. coli colonies increased when they were cultured with the supernatant of MSCs-dia, with or without LPS stimulation, compared with the E. coli cultured with MSCs-c supernatant. Human macrophages were co-cultured with either MSCs-dia or MSCs-c, for 24 hours, and then cultured with heat-inactivated E. coli. Bacterial phagocytosis was reduced after macrophages were co-cultured with MSCs-dia. Gene expression of antibacterial peptide LL-37 and indoleamine 2,3-dioxygenase (IDO) by MSCs-dia was reduced as compared with MSCs-c. The supernatant of MSCs-dia and MSCs-c was applied to a 42-cytokine antibody array. While the cytokine profiles of MSCs-dia and MSCs-c were largely similar, the productions of MCP-1 and IL-6 distinguished MSCs-dia from MSCs-c in response to LPS treatment. In conclusion, MSCs-dia were less inhibitive of the growth of bacteria and compromised in regulation of macrophages for bacterial phagocytosis. The reduced expression of IDO and LL-37 and an altered cytokine profile in MSCs-dia should be taken into consideration in developing cell therapies for diabetic infection.
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