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Towards a Cell-Free Treatment for Kidney Injury

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Review of “Human Kidney-Derived Cells Ameliorate Acute Kidney Injury without Engrafting into Renal Tissue” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Recent animal model studies describing how the intravenous transplantation of CD133+ putative kidney progenitor cells [1, 2] ameliorated injury by engrafting into the kidneys and differentiating into specialized renal cells [2, 3] have raised hope for acute kidney injury sufferers. To build upon these encouraging studies, the laboratory of Bettina Wilm (University of Liverpool, UK) aimed to assess the regenerative/reparative ability of human kidney progenitor cells in a rat model of AKI by employing a novel transcutaneous device to monitor changes to kidney function [4]. 

Their new STEM CELLS Translational Medicine study now demonstrates that improvements to kidney function did not require engraftment of kidney progenitors and the production of specialized cells and, instead, repair relied on paracrine or endocrine secreted factors [5]. With this knowledge in hand, can we create a safe and effective cell-free treatment for kidney injury?

While progenitor cells normally carry a potent regenerative potential, the initial experiments of this new study suggested that systemic delivery of both CD133+ (putative progenitors) and CD133- cells (non-progenitors) derived from human primary kidney cell cultures enhanced kidney function to a similar degree. Functional assessments utilized a novel transcutaneous device that detected changes to a fluorescent molecule (fluorescein isothiocyanate-sinistrin) exclusively filtered by the kidneys.

Analysis of cell distribution indicated a lack of donor cell engraftment in the kidneys and, instead, the study soon discovered that the transplanted cells actually accumulated in the lungs and died soon after administration. However, while in the lungs, kidney cells initiated macrophage infiltration, phagocytosis, and, importantly, the release of an anti-inflammatory interleukin (IL10), which the authors suggest may be the driving force behind the engraftment-free improvement in kidney function.

Overall, this new study suggests that, firstly, CD133 expression does not necessarily mediate any ameliorative effects itself and, secondly, kidney injury repair does not require human kidney cell engraftment and instead relies on paracrine or endocrine acting factors! The authors propose that the analysis of how dying cells modulate immune effector cells may permit the construction of a safe and effective cell-free treatment for kidney injury.

Keep yourself tuned to the Stem Cells Portal to discover all the updates on this exciting strategy for the treatment of kidney injury!

References

  1. Bussolati B, Bruno S, Grange C, et al. Isolation of renal progenitor cells from adult human kidney. Am J Pathol 2005;166:545-555.
  2. Ronconi E, Sagrinati C, Angelotti ML, et al. Regeneration of glomerular podocytes by human renal progenitors. J Am Soc Nephrol 2009;20:322-332.
  3. Angelotti ML, Ronconi E, Ballerini L, et al. Characterization of renal progenitors committed toward tubular lineage and their regenerative potential in renal tubular injury. Stem Cells 2012;30:1714-1725.
  4. Schock-Kusch D, Sadick M, Henninger N, et al. Transcutaneous measurement of glomerular filtration rate using FITC-sinistrin in rats. Nephrol Dial Transplant 2009;24:2997-3001.
  5. Santeramo I, Herrera Perez Z, Illera A, et al. Human Kidney-Derived Cells Ameliorate Acute Kidney Injury Without Engrafting into Renal Tissue. STEM CELLS Translational Medicine 2017;6:1373-1384.