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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.