TY  - BOOK
AU  - Cho, Young
AU  - Feltham, Tyler
AU  - Mitchell, Reed
AU  - Paudel, Sharada
AU  - Schon, Lew C
AU  - Zhang, Zijun
TI  - Compromised Antibacterial Function of Multipotent Stromal Cells in Diabetes
SN  - 1547-3287
PY  - 2019///
KW  - *Antimicrobial Cationic Peptides/me [Metabolism]
KW  - *Cytokines/me [Metabolism]
KW  - *Diabetes Mellitus/im [Immunology]
KW  - *Phagocytosis
KW  - *Pluripotent Stem Cells/im [Immunology]
KW  - Aged
KW  - Antimicrobial Cationic Peptides/ge [Genetics]
KW  - Bone Marrow Cells/im [Immunology]
KW  - Cells, Cultured
KW  - Chemokine CCL2/ge [Genetics]
KW  - Chemokine CCL2/me [Metabolism]
KW  - Cytokines/ge [Genetics]
KW  - Escherichia coli/de [Drug Effects]
KW  - Female
KW  - Humans
KW  - Indoleamine-Pyrrole 2,3,-Dioxygenase/ge [Genetics]
KW  - Indoleamine-Pyrrole 2,3,-Dioxygenase/me [Metabolism]
KW  - Macrophages/im [Immunology]
KW  - Male
KW  - Middle Aged
KW  - MedStar Union Memorial Hospital
KW  - Orthobiologic Laboratory
KW  - Orthopaedic Surgery
KW  - Journal Article
N2  - 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
UR  - https://dx.doi.org/10.1089/scd.2018.0219
ER  -