Regenerative treatments for kidney diseases: The closest and fastest strategies to solving related medical and economic problems

Abstract

Recent advances in developmental biology and stem cell biology have led to the increased availability of extrarenal stem cells, including mesenchymal/stromal stem cells (MSCs), renal stem or progenitor cells isolated from embryonic and adult kidneys, and kidney lineage cells or tissues generated from human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human-induced pluripotent stem cells. Regenerative medicine strategies for kidney diseases are largely categorized into the transplantation of reconstructed kidney organs and cell therapies.Reconstruction is being attempted by hPSC-derived kidney lineage cells with various strategies, such as self-organization, interspecies blastocyst complementation, utilization of a xenogeneic organ niche, decellularization and repopulation, and 3D bioprinting. However, cell therapies using extrarenal stem cells, such as MSCs, and renal stem or progenitor cells derived from embryonic and adult kidneys or differentiated from hPSCs have been investigated in animal models of both acute kidney injury and chronic kidney disease. Indeed, multiple clinical trials using MSCs, bone marrow stem cells, and kidney-derived cells have already been carried out. This review summarizes the current status and future perspective of kidney regenerative medicine strategies and discusses the closest and fastest strategies to solving the medical and economic problems associated with kidney diseases. K E Y W O R D Skidney disease, regenerative medicine, stem cell How to cite this article: Osafune K. Regenerative treatments for kidney diseases: The closest and fastest strategies to solving related medical and economic problems.

Regrow or Repair: An Update on Potential Regenerative Therapies for the Kidney

“…The xenogenic generation of human kidneys within a nonhuman host animal via blastocyst complementation is being investigated as an alternative. 177 A proof-of-concept experiment for this approach delivered mouse pluripotent stem cells into blastocysts of either a Sall1-deficient mouse or rat strain, resulting in a kidney entirely generated from the donor, except the collecting ducts and microvasculature. 178,179 Because the vasculature was host-derived, were this to be successful using hPSCs into a xenogenic host, the resulting chimeric organ would elicit hyperacute rejection.…”

“…The staggering complexity of kidney architecture is such that recreating such an intricate organ in totality may never be possible, or even to replace selected renal functions, with stem cell–derived engineered tissue. The xenogenic generation of human kidneys within a nonhuman host animal via blastocyst complementation is being investigated as an alternative 177 . A proof-of-concept experiment for this approach delivered mouse pluripotent stem cells into blastocysts of either a Sall1 -deficient mouse or rat strain, resulting in a kidney entirely generated from the donor, except the collecting ducts and microvasculature 178 , 179 .…”