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Kidney Hypothermic Perfusion with Mesenchymal Stromal Cells or Microvesicles Protects Rat Kidney from Ischemia By Upregulation of Cell Energy Metabolism and Ion Membrane Transport Key Genes

ABSTRACT: We evaluated in a rat model of Donor after Circulatory Death (DCD) the effects of pretransplant kidney conditioning with Mesenchymal Stromal Cells (MSC) or MSC derived microvescicles (MV) on ischemic injury. Fisher rats (F) were used as kidney donors, Transgenic Sprague-Dawley rats expressing Enhanced Green Fluorescence Protein (EGFP) as MSC donors. After 20 min of warm ischemia nephrectomy was performed and kidneys were perfused with Belzer solution (BS), BS supplemented with MSC (MSC) or with MV (MV) for 4 h, at 4°C. Renal damage was evaluated by histology, renal gene expression by microarray analysis and RT-PCR. Malondialdehyde, lactate, LDH, glucose and pyruvate were measured in effluent fluid. MSC/MV kidneys showed a significant minor global ischemic damage and up-regulation of three genes encoding proteins that improve cell energy metabolism (Isocitrate dehydrogenase 2, NADH dehydrogenase Fe-S protein 8, Pyruvate dehydrogenase beta) and three genes encoding proteins involved in ion membrane transport (Calbindin 1, Monocarboxylate transporter 1, Vacuolar H+-ATPase d2 subunit). Lactate, LDH and malondialdehyde in effluent fluid were significantly lower in MSC/MV kidneys than BS. Glucose was lower while pyruvate higher in MSC/MV effluent than BS, suggesting a larger use of energy substrates by MSC/MV kidneys. MSC/MV perfusion of kidneys in addition to BS through HMP protects from ischemia injury by preserving the enzymatic machinery essential for cell viability and prepares kidney to reperfusion damage.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE84563 | GEO | 2017/07/21

SECONDARY ACCESSION(S): PRJNA329647

REPOSITORIES: GEO

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