Considerations on the development of a model of kidney bioengineering and regeneration in rats

Abstract

Evaluation of: Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19(5), 646–51 (2013).

Emergent technologies of regenerative medicine have shown immense potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered ex vivo in the laboratory. So far, clinical translation has been possible for simple, hollow organs, whereas the bioengineering and regeneration of complex modular organs (namely, kidneys, hearts, livers, lungs and small bowel) remains far from our grasp. In the case of the kidney, the bioengineering and regeneration of renal organoids requires a supporting scaffold that approximates the biochemical, spatial and vascular relationships of the native kidney extracellular matrix. A recent report describes the use of rodent kidneys to generate whole organ, three-dimensional scaffolds. These scaffolds were subsequently seeded with rat neonatal kidney cells to reconstitute the parenchymal cell compartment and with human umbilical venous endothelial cells to reconstitute the endothelium and allow implantation. Once assembled and allowed to mature in bioreactors, the so-obtained constructs were able to exert some function peculiar to the kidney both in vitro and in vivo after implantation in rodents. In this invited commentary, we will address the most critical topics of organ regeneration starting from the above-mentioned experience with the kidney but eventually embracing the whole field of complex modular organs bioengineering.

Keywords::

• extracellular matrix
• function
• kidney bioengineering
• organ bioengineering
• regeneration
• scaffold
• transplantation
• urine

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Organ bioengineering and regeneration represents the new Holy Grail for organ transplantation as it has the potential to address and solve the two most urgent needs: the identification of a new, inexhaustible source of organs manufactured from patient’s own cells, and immunosuppression-free transplantation (namely, tolerance).

• • Cell-scaffold technology (CST) seems to offer the quickest route to clinical translation, based on the idea that cellular welfare requires a supporting framework that, in organ bioengineering and regeneration, is referred to as a ‘scaffold’. Scaffolds generated from native organs’ extracellular matrix (ECM) are probably the most appropriate and convenient because they maintain innate architecture and composition, intact and patent vasculature and growth factors.

• • While current technology allows production of natural ECM scaffolds, the reconstitution of the cellular compartment post-decellularization remains challenging and represents the main hurdle to succeed. So far, it seems that cells and ECM do not really integrate in a fully functioning system, as occurs in nature. Research should aim at the understanding of the mechanisms of interaction among cells and ECM, as well as of the role of growth factors of which the matrix is a reservoir.

• • Acquisition of in-depth knowledge of the developmental mechanisms of the single organs will be crucial for designing appropriate strategies which reproduce, in suitable bioreactors, the key steps of organ ontogenesis.