Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model.

Acute kidney injury (AKI) after transplantation of human deceased donor kidneys is associated with upregulation of tubular toll like receptor 4 (TLR4), but whether TLR4 is required for AKI is unknown. We hypothesized that TLR4 knockout mice (TLR4KO) subjected to cold ischemia followed by kidney transplant (CI + Txp) would be protected from AKI. C57Bl/6J wild type or TLR4KO kidneys were subjected to CI + Txp into wild type recipients.

The impact of Caspase-1 deletion on apoptosis and acute kidney injury in a murine transplant model.

Background: Caspase-1 knockout mice (Casp1KO) are protected from Acute Kidney Injury (AKI) after warm ischemia/reperfusion injury in non-transplant models. Since Caspase-1 plays a central role as an inflammatory response initiator, we hypothesized that Casp1KO mice would be protected from AKI following transplant.

Methods: Renal tubular cells (RTECs) were subjected to cold storage and rewarming (CS/REW).

A Standardized Warm Ischemia Time for the Induction of Injury in Murine Kidney Transplants.

One of the cornerstone research models used in our laboratories is the induction of ischemic injury through cold ischemia followed by warm ischemia to donor kidneys to mimic the clinical realities of transplantation. The experimental design of the present study included bilateral nephrectomies on the day of syngeneic kidney transplant, with serum creatinine measured 24 hours postoperatively to measure acute function. Cold ischemia time in these experiments was always 30 minutes, and warm ischemia time was not standardized but always recorded.

Injury Pathways That Lead to AKI in a Mouse Kidney Transplant Model.

Background: Prolonged cold ischemia (CI) is a risk factor for acute kidney injury after kidney transplantation. We endeavored to determine the pathways involved in the development of tubular cell injury and death before and after transplantation. We hypothesized that ex vivo cold storage before transplant would produce a different injury phenotype to that seen after engraftment in kidney transplants with or without CI.

C-kit-derived CD11b cells are critical for cardiac allograft prolongation by autologous C-kit progenitor cells.

Autologous C-kit cells robustly prolong cardiac allografts. As C-kit cells can transdifferentiate to hematopoietic cells as well as non-hematopoietic cells, we aimed to clarify the class(es) of C-kit-derived cell(s) required for cardiac allograft prolongation. Autologous C-kit cells were administered post-cardiac transplantation and allografts were evaluated for C-kit inoculum-derived cells.