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Human Peripheral Blood Mononuclear Cells Incubated in Vasculogenic Conditioning
Medium Dramatically Improve Ischemia/Reperfusion Acute Kidney Injury in Mice
#MMPMID29737200
Ohtake T
; Kobayashi S
; Slavin S
; Mochida Y
; Ishioka K
; Moriya H
; Hidaka S
; Matsuura R
; Sumida M
; Katagiri D
; Noiri E
; Okada K
; Mizuno H
; Tanaka R
Cell Transplant
2018[Mar]; 27
(3
): 520-530
PMID29737200
show ga
Acute kidney injury (AKI) is a major clinical problem that still has no
established treatment. We investigated the efficacy of cultured human peripheral
blood mononuclear cells (PBMNCs) for AKI. Ischemia/reperfusion injury (IRI) was
used to induce AKI in male nonobese diabetic (NOD/severe combined
immunodeficiency) mice aged 7 to 8 wk. PBMNCs were isolated from healthy
volunteers and were subjected to quality and quantity controlled (QQc) culture
for 7 d in medium containing stem cell factor, thrombopoietin, Flt-3 ligand,
vascular endothelial growth factor, and interleukin 6. IRI-induced mice were
divided into 3 groups and administered (1) 1 × 10(6) PBMNCs after QQc culture
(QQc PBMNCs group), (2) 1 × 10(6) PBMNCs without QQc culture (non-QQc PBMNCs
group), or (3) vehicle without PBMNCs (IRI control group). PBMNCs were injected
via the tail vein 24 h after induction of IRI, followed by assessment of renal
function, histological changes, and homing of injected cells. Blood urea nitrogen
and serum creatinine (Cr) 72 h after induction of IRI in the QQc PBMNCs group
dramatically improved compared with those in the IRI control and the non-QQc
PBMNCs groups, accompanied by the improvement of tubular damages. Interstitial
fibrosis 14 d after induction of IRI was also significantly improved in the QQc
PBMNCs group compared with the other groups. The renoprotective effect noted in
the QQc PBMNCs group was accompanied by reduction of peritubular capillary loss.
The change of PBMNCs' population (increase of CD34+ cells, CD133+ cells, and
CD206+ cells) and increased endothelial progenitor cell colony-forming potential
by QQc culture might be one of the beneficial mechanisms for restoring AKI. In
conclusion, an injection of human QQc PBMNCs 24 h after induction of IRI
dramatically improved AKI in mice.
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