Extracellular membrane vesicles from umbilical cord blood‐derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioning

• DOI: 10.3402/jev.v2i0.21927
• Publication Date: 2013-12-10T11:48:28Z
• Authors: Lotta Kilpinen; Ulla Impola; Lotta Sankkila; Ilja Ritamo; Maria Aatonen; Sami Kilpinen; Jarno Tuimala; Leena Valmu; Jouko Levijoki; Piet Finckenberg; Pia Siljander; Esko Kankuri; Eero Mervaala; Saara Laitinen
• Keywords: CD63; Exosome; Extracellular vesicles

Mesenchymal stromal cells (MSC) are shown to have a great therapeutic potential in many immunological disorders. Currently the effect of MSCs is considered be mediated via paracrine interactions with immune cells. Umbilical cord blood an attractive but still less studied source MSCs. We investigated production extracellular membrane vesicles (MVs) from human umbilical derived (hUCBMSC) presence (MVstim) or absence (MVctrl) inflammatory stimulus.hUCBMSCs were cultured serum free media without IFN-γ and MVs collected conditioned by ultracentrifugation. The protein content analyzed mass spectrometry. Hypoxia induced acute kidney injury rat model was used analyze vivo T-cell proliferation induction regulatory T co-culture assays.Both MVstim MVctrl showed similar modulation activity vitro, only MVctrls able protect kidneys reperfusion vivo. To clarify this difference functionality we made comparative spectrometric analysis MV contents. stimulation dramatic changes MVs. Complement factors (C3, C4A, C5) lipid binding proteins (i.e apolipoproteins) found MVctrls, whereas contained tetraspanins (CD9, CD63, CD81) more complete proteasome complex accompanied MHCI. further discovered that differently produced pools specific Rab suggesting same cells, depending on external signals, produce originating different intracellular locations.We demonstrate both vitro models detailed molecular characteristics conditioning influence functional properties revealing complexity MSC regulation.