Human Peripheral Blood Mononuclear Cells Incubated in Vasculogenic Conditioning Medium Dramatically Improve Ischemia/Reperfusion Acute Kidney Injury in Mice

Abstract

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 × 106 PBMNCs after QQc culture (QQc PBMNCs group), (2) 1 × 106 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.

LncRNA TapSAKI promotes inflammation injury in HK-2 cells and urine derived sepsis-induced kidney injury

“…Sepsis is a systemic inflammatory response syndrome caused by bacterial, viral or fungal infection which causes organ injuries, and the incidence of acute kidney injury in patients with severe sepsis can reach up to 60% . Acute kidney injury can be diagnosed by increased blood urea nitrogen (BUN) and serum creatinine . However, treatment of sepsis‐induced kidney injury is not satisfactory.…”

“…[1] Acute kidney injury can be diagnosed by increased blood urea nitrogen (BUN) and serum creatinine. [2,3] However, treatment of sepsis-induced kidney injury is not satisfactory. Therefore, it is necessary to find effective therapeutic targets for sepsis-induced kidney injury.…”

Regeneration-Associated Cells Improve Recovery from Myocardial Infarction through Enhanced Vasculogenesis, Anti-inflammation, and Cardiomyogenesis

“…Transplanted RACs initiated angiogenesis in host tissues in the same manner as in previously described ischemia disease models [21,29,30]. In vitro, rat QQMNC EPC-CFUs were increased, mostly with dEPC-CFUs, which are capable of forming "tube-like" structures.…”

“…This method for QQMNC generation is based on an established culture method to increase the quality and quantity of the EPC population, comprising, for example, of CD34+ and CD133+ cells [20]. Interestingly, this vasculogenic signaling condition can educate naïve PBMNCs to not only expand EPCs but also to convert hematopoietic 14/25 cells into populations responsible for vascular and tissue regeneration 21,29 . With human QQMNCs, definitive colony forming EPCs increased, and macrophages and T lymphocytes became phenotypically polarized into their respective angiogenic, anti-inflammatory, and regenerative subsets.…”

“…In this regard, QQMNCs are considered a representative "regeneration-associated cell" (RAC) population for ischemia or regenerative organs. This therapeutic concept was evaluated by several animal experiments, involving hindlimb ischemia, acute ischemic kidney injury, and diabetic wound healing mouse models, which analyzed the potential of QQMNCs to induce recovery organ function [21,29,30].…”