New strategies in kidney regeneration and tissue engineering.
OBJECTIVE
The severe shortage of suitable donor kidneys limits organ transplantation to a small fraction of patients suffering from end-stage renal failure. Engineering autologous kidney grafts on-demand would potentially alleviate this shortage, thereby reducing healthcare costs, improving quality of life, and increasing longevity for patients suffering from renal failure.


RESULTS
Over the past 2 years, several studies have demonstrated that structurally intact extracellular matrix (ECM) scaffolds can be derived from human or animal kidneys through decellularization, a process in which detergent or enzyme solutions are perfused through the renal vasculature to remove the native cells. The future clinical paradigm would be to repopulate these decellularized kidney matrices with patient-derived renal stem cells to regenerate a functional kidney graft. Recent research aiming toward this goal has focused on the optimization of decellularization protocols, design of bioreactor systems to seed cells into appropriate compartments of the renal ECM to nurture their growth to restore kidney function, and differentiation of pluripotent stem cells (PSCs) into renal progenitor lineages.


CONCLUSIONS
New research efforts utilizing bio-mimetic perfusion bioreactor systems to repopulate decellularized kidney scaffolds, coupled with the differentiation of PSCs into renal progenitor cell populations, indicate substantial progress toward the ultimate goal of building a functional kidney graft on-demand.
aComprehensive Transplant Center, Northwestern University Feinberg School of Medicine bDepartment of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois cGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California dInstitute for BioNanotechnology in Medicine, Northwestern University, Chicago Illinois eChemistry of Life Processes Institute fDepartment of Biomedical Engineering, Northwestern University, Evanston, Illinois, USA.
Joseph S
JS
Uzarski
Yun
Y
Xia
Juan C I
JC
Belmonte
Jason A
JA
Wertheim
D000818:Animals; D057005:Bioengineering / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D005109:Extracellular Matrix; D006801:Humans; D007668:Kidney / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000502:physiology*; D012038:Regeneration; D054457:Tissue Scaffolds