NephMadness 2014 • Regeneration • First Round Results

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Parietal epithelial cells versus Renin lineage cells

Winner: Parietal epithelial cells

parietal epiThe parietal epithelial cells (PECs) migrate their way to victory over the upstart renin lineage cells. This was an up and down game but the PECs proved dominant and took over this contest in the second half. The youth and inexperience of the renin-lineage cell team proved too much of a hurdle to overcome. The proliferative capacity of the PECs were in full display. The tipping point came with evidence that a subpopulation of proliferative PECs may lead to collapsing FSGS in humans. Renin-lineage cell put up a good fight. Interestingly, evidence of renin-lineage cells becoming PECs has been reported. So, I guess you could say that the renin-lineage cell’s top player transferred to the PEC team in order to advance. How PECs function in physiology and disease is still a matter of debate. It is likely that PECs  in some instances are good and useful as a progenitor pool to damaged podocytes and other cells. While, in certain circumstances, such as collapsing FSGS, PECs can actually be harmful. The PECs are now in the kidney spotlight and more research will help to elucidate their role in kidney disease. The PECs move on to round 2 of NephMadness 2014 to face the formidable team renal pericytes.

Renal pericytes versus Epithelial to mesenchymal transition

Winner: Renal pericytes

pericyteTeam pericytes wins against team EMT in what will for sure go down as one of the greatest first round matchups of NephMadness history. The anticipation was palpable for this one. Team EMT had all of the tradition going for it (like a John Wooden led UCLA). However, team pericyte as the Cinderella of NephMadness showed how much versatility this niche cell type has. Fibrosis is a hot topic in multiple areas of medical research and this is proving to be true in the kidney field as well. The end-game for all forms of kidney damage is persistent fibrosis and understanding the mechanisms governing fibrosis will be critical in order to successfully target progressive kidney failure. EMT has been studied for the longest duration in the field of kidney regeneration. This matchup by far is the most controversial in the regeneration bracket.  Several groups have demonstrated by lineage tracing that the bulk of fibroblasts that accumulate in the kidney after ureteral obstruction in the mouse (an experimental model of CKD) are of renal tubular cell origin. However, Lin et al demonstrated that it is the pericyte that transforms into the collagen-producing myofibroblast. I’m sure we haven’t heard the last of this battle. EMT has been around for a while and I’m sure they will be back to NephMadness soon. Team pericytes will have a tough matchup with the PECs. Both have youth and the ability to migrate and potentially differentiate into either podocytes or fibroblasts. This will be an interesting matchup.

Self-duplication of tubules versus Tubule regeneration from resident stem cells

Winner: Tubule regeneration from resident stem cells

stem cellTeam stem cell defeats self-duplication of tubules for a spot in the second round against bioartificial kidney. This was a close one. Stem cells have continued to garner a lot of attention and this is rightfully so. Will resident stem cells hold the key to successful kidney regeneration? How did stem cells defeat direct tubule regeneration? First, evidence of a stem cell population capable of tubule differentiation has been identified in close proximity to the renal proximal tubule and distal convoluted tubule. The self duplication fans can hang their hats on the study by kusaba et al that show that a majority of cellular proliferation of injured tubules was from reduplication of terminally differentiated tubular cells and not from expansion of a progenitor cell population. This matchup will likely continue for years to come. However, with the recent momentum of stem cells it could be fight to the finish. The next match for stem cells will be a dangerous one. The mighty bioartificial kidney is lurking.

Bioartificial kidney versus Hypertrophy

Winner: Bioartificial kidney

biokidneyHypertrophy was no match for bioartificial kidney. Bioartificial kidney won hands down as team hypertrophy was stuck in the 80s with half court offense and an inability to run to court.  Team bioartificial kidney was still riding high from the Nature Medicine report of the functional bioartificial kidney. This was quite a feat as the reproduction of a complex 3-dimensional kidney still seemed years away. The report by Song et al was years ahead of its time. However, whether or not this bioengineered kidney would be able to sustain the life of the rat for an extended period of time is unknown. The other exciting story was from Taguchi et al. This group reconstituted nephrons in vitro and implanted these beneath the renal capsule of mice and new vascularization commenced. Team hypertrophy was just happy to be in the big dance this year it seemed. Too many injuries. The fundamental principle of hypertrophy is how an individual cell enlarges, by increasing its protein content, without an increase its DNA content. Is bigger always better? Wiggins et al demonstrated that podocytes when lost due to cell death, their neighbor podocyte will undergo hypertrophy to cover the bare area. This is called compensatory hypertrophy. However, with time, these large cells produce an excess of deleterious factors such as cytokines, and augment rather than reduce disease. This was the Achilles heal of team hypertrophy and was their ultimate undoing. Team bioartificial kidney will go up against kidney stem cells in what will be a great matchup as far as skill is concerned. It is anyone’s guess who will win this battle.

-Cartoon Illustrations by John K. Roberts, MD, MS

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