Kidney regeneration. The stride continues…

The past two weeks have been exciting for the field of regenerative medicine in nephrology. Two papers demonstrated the feasibility of developing kidney cells from human pluripotent stem cells. One from the USA by Dr Joseph Bonventre’s group at the Renal Division of the Brigham and Women’s Hospital (Morizane, Lam et al. Nat Biotechnol 2015) and one from Australia by Dr Melissa Little’s Group at University of Melbourne (Takasato et al. Nature 2015).

The major breakthrough of these publications is that they were able to generate with a high efficiency mature nephrons (with podocytes, proximal tubules, loops of Henle and distal tubules) starting from nephron progenitor cells!

Albert Lam, one of the co-authors of the Nat Biotechnol paper, stated that: “We established a differentiation protocol that would mimic the stages of nephron formation as closely as possible. Our approach in recapitulating the steps of kidney development resulted in a highly efficient protocol for generating kidney organoids. The ability to do this using induced pluripotent stem (iPS) cells, which are derived from skin or blood cells of patients, allows the creation of kidney tissue without ethical concerns and allows the tissue to be “personalized”, that is, generated from a particular patient. If in the future the tissue is re-implanted back into the patient, the immune response may then be very limited since the tissue will be recognized as self.” This achievement has an enormous potential impact on a variety of clinical and translational applications, including kidney tissue bioengineering to replace lost kidney tissue, renal assist devices to treat acute and chronic kidney injury, drug toxicity screening, screening for novel therapeutic agents, and human kidney disease modeling.

Albert kindly shared with me that I shouldn’t be anxious yet about my job as a transplant nephrologist since more years are needed to develop a full organ incorporating the blood supply and urinary collecting system. I selfishly hope so…

Figure above: Nephron 3D structure 28 days after protocol initiation demonstrating the presence of markers of distal tubules (CDH1), podocytes (PODXL) and proximal tubules (LTL)

NephMadness 2014 Part 3 - Kidney Regeneration Bracket

The kidney regeneration bracket is full of heavy weights as usual! However, not being in the field myself one team jumped out for me, Bioartificial Kidney. As the authors of this piece say this is truly the holy grail of nephrology. This field was taken out of the realm of captain Kirk and Dr Spock in 2013 with the publication of reports of a paper in Nature Medicine. In this experiment the authors decellularized a rat kidney a reperfused it with epithelial and endothelial cells. Remarkably this kidney made urine in vitro. The stem cell field was again put under the spot light this year after a publication in Nature by Obokata et al. They reported the discovery of an unexpected phenomenon of somatic cell reprogramming into pluripotent cells by exposure to sublethal stimuli, which they called stimulus-triggered acquisition of pluripotency (STAP). This method basically takes somatic cells puts them in mild acid and they come out as pluripotent step cells! Yes, it sounds unbelievable and it is turning out that way to. Other groups have not been able to reproduce these results using this ‘simple’ technique. Furthermore, the authors have recently submitted an erratum reporting that some images in their manuscript were mistakenly included! Emmm!