Bioengineering strategies for nephrologists: kidney was not built in a day

Figures & data

Figure 1. Current bioengineering strategies to build kidneys.

Table 1. Summary of advantages, disadvantages, and clinical relevance of each bioengineering approaches to kidney (re)generation.

	Advantages	Disadvantages	Clinical relevance	Ref.
Transplantable kidney from another organism
Xenotransplantation	– Pig kidneys have similar size and internal anatomy compared to human organs – Genetic engineering can make pig kidneys safer for xenotransplants	– Ethical and legal issues – Risks of transmission of infectious diseases – Immunological barrier	Increase kidney availability in terms of number, time, and location	[18,21,23]
Chimeras	– Chimeras allow to grow human kidneys in an animal host, avoiding xenotransplantation issues such as immunologic barrier, differences in organ size and physiology	– Limited contribution of human PSCs to post-implantation embryos – Development of organs formed of mixed donor/host cells	Increase kidney availability in terms of number, time, and location	[47,51]
Building bioengineered kidneys
Bioartificial kidneys	– Bioartificial kidneys are biologic-artificial hybrids that combine continuous blood filtration with tubular, metabolic and endocrine functions – Potentially industrial production	– Technical feasibility – Costs of production and storage	Allow to move dialysis patients outside the clinic	[53,55,56,69]
Kidney-derived scaffolds	– Faithfully preserve the kidney matrix composition – Evidence of urine filtration following recellularization – Efficient repopulation of kidney vasculature	– Lack of efficient recellularization protocol for the nephron – Possible host immunological response to the decellularized scaffold – The need of a very high number of cells to successfully repopulate an entire human kidney	Reconstitute a functional kidney for transplantation	[75,77,82]
Development of self-organizing nephrons
Kidney organoids	Kidney organoids model anatomical and functional hallmarks of the real organ	– Lack of vascular network and urinary exit tract – More immature than adult kidney – Difficulties to obtain higher-order structures – Poor reproducibility	Use for personalized-disease modeling and drug toxicity testing	[90,91]
Kidney-on-a-chip	– Microfluidics-based systems reproduce the physiology of nephron portions – Automation and high throughput screening	Analysis restricted to a portion of the nephron	Use for personalized-disease modeling and drug toxicity testing	[106,108,109,124,126,127,138,143]
3D bioprinting	−3D kidney bioprints model the tissue complexity and its microenvironment – 3D kidney organoids are bioprinted for high-throughput screening	Analysis restricted to a portion of the nephron	Modeling and drug toxicity testing	[155–157]

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