Developmentally inspired synthetic kidney engineering

Area of Science:

• Biomedical Engineering
• Developmental Biology
• Stem Cell Biology

Background:

• Stem cell-derived kidney tissues show promise for renal replacement therapy but face challenges in clinical translation, including variability, missing cell types, immaturity, and scalability.
• Current limitations hinder the clinical application of engineered kidney tissues, necessitating novel strategies to improve outcomes and feasibility.

Purpose of the Study:

• To present a 'developmental engineering' strategy for in vitro kidney tissue construction.
• To leverage principles of embryonic kidney development for guiding tissue formation.
• To outline a blueprint for scalable and translationally viable renal replacement tissues.

Main Methods:

• Utilizing spatial and temporal cues inspired by in vivo embryonic development to guide multiscale tissue structure formation in vitro.
• Employing synthetic biology tools, spatial patterning, and controlled tissue microenvironments to initiate and direct the development of specific tissue motifs.
• Proposing a vision for scalable developmental engineering through guiding and linking tissue motifs and bridging self-organization discontinuities via direct assembly.

Main Results:

• Demonstration of a developmental engineering strategy that guides multiscale structure formation in vitro.
• Highlighting the potential of synthetic biology and microenvironment control to instigate and guide desired tissue motif development.
• Articulating a blueprint for developmental engineering of translationally viable renal replacement tissues.

Conclusions:

• The presented developmental engineering strategy offers a promising approach to overcome limitations in stem cell-derived kidney tissue engineering.
• This strategy, inspired by embryonic development, can guide the formation of complex tissue structures in vitro.
• The approach holds potential for scalable production of functional renal replacement tissues and may be applicable to other solid organs.