The lack of transplantable kidneys is an unavoidable problem for those of us who practice Nephrology. Whilst government policies and extended criteria for donor organs have a role to play in solving this problem, it has always seemed to me that science is going to have to serve us up a definitive solution.
Although many of us appreciate that induced pluripotent stem cells (iPSCs) will likely form part of the answer to this question, it is more difficult to visualise how iPSCs could be used to reconstitute a complex multi-cell organ such as the kidney. Additionally, since the emergence of 3D printing we have had media friendly stories of printed kidneys without much information about what will be used as the ‘ink’ in the printer.
A paper in this month’s Cell Stem Cell may hint at the future. Firstly, the authors worked out the developmental origins of the metanephric mesenchyme (MM), the embryonic tissue that generates most elements of a functioning kidney (see diagram). The group then used this information to derive MM from PSCs and found that this derived MM successfully reconstituted glomeruli and proximal and distal tubules in vitro. Furthermore, when these generated nephrons were transplanted beneath the renal capsule of mice they showed new vascularisation suggesting they may be functional.
So, is the answer to our transplantation problem to use these authors’ protocol to derive lots of MM which can then be 3D printed around a small core of functioning renal tissue to make a working organ? Well, a number of issues remain. Firstly, as can be seen from the diagram, the collecting duct is derived from the separate ureteric bud. Therefore, it is not included in this model and successful combination of these structures would likely be needed to make a truly functional nephron. Perhaps most glaring is that the Cell Stem Cell paper makes no assessment of the excretory function of these derived nephrons.
In conclusion this is probably only “a good start” but I think it represents significantly more progress than any number of eye catching 3D printer stories.
Hi Tom – thanks for this post and for bringing attention to this emerging science. This is one of four papers that were released online at the end of the year, the others being a Nature Cell Biology paper from Juan Belmonte's group, a Nature Cell Biology paper from Melissa Little's group, and one in JASN from our group — all with the focus of using pluripotent stem cells for kidney regeneration. You're absolutely right. These findings collectively mark a first step towards using human stem cells to generate kidney tissue, but we are still quite a ways from generating human-only kidney structures. Our hope is that these papers will now spark more interest and support in reaching this goal.