Kidney regeneration using stem cells and acellular whole organ scaffolds: Perspective and recent developments

Abstract

Several tissue engineering strategies have been proposed for the regeneration of whole kidney organs. Embryonic stem (ES) cells have the benefit of pluripotency but present challenges for the choice of appropriate growth factors to induce functional fully mature tissue. Use of embryonic renal precursor structures (i.e. the metanephros) is very promising, but their fetal sources can have potential ethical and immunologic shortcomings. Seeding of acellular tissue scaffolds with mature cells has had success, but has been limited by simple organ architecture not requiring complex configurations of large numbers of cell types. We explored the use of decellularized intact kidneys for matrix-to-cell signaling to induce differentiation of embryonic stem cells. Rat kidneys underwent detergent (ionic and nonionic), osmotic, enzymatic and mechanical decellularization and were seeded via the artery or ureter with murine ES cells. The organs were cultured for up to 2 weeks with static as well as pumped pulsatile media conditions. The cells adhered to basement membranes, multiplied and showed evidence for lumen formation. Without the addition of growth factors there was evidence for differentiation by light microscopy, immune-histochemical staining and RT-PCR genetic analyses. These preliminary results stress the importance of matrix-cell as well as cell-cell and cell-matrix signaling for differentiation, and support further investigations of the use of scaffolds in tissue engineering and regeneration. © 2009 Springer-Verlag.