Abstract
In this decade, substantial progress in the fields of developmental biology and stem cell biology has ushered in a new era for three-dimensional organ regenerative therapy. The emergence of novel three-dimensional cell manipulation technologies enables the effective mimicking of embryonic organ germ formation using the fate-determined organ-inductive potential of epithelial and mesenchymal stem cells. This advance shows great potential for the regeneration of functional organs with substitution of complete original function in situ. Organoids generated from multipotent stem cells or tissue stem cells via establishment of an organ-forming field can only partially recover original organ function owing to the size limitation; they are considered ‘mini-organs’. Nevertheless, they hold great promise to realize regenerative medicine. In particular, regeneration of a functional salivary gland and an integumentary organ system by orthotopic and heterotopic implantation of organoids clearly points to the future direction of organ regeneration research. In this review, we describe multiple strategies and recent progress in regenerating functional three-dimensional organs, focusing on ectodermal organs, and discuss their potential and future directions to achieve organ replacement therapy as a next-generation regenerative medicine.
Highlights
Numerous advances in various research fields, including developmental biology, stem cell biology and tissue engineering technology, have facilitated regenerative medicine [1,2,3]
We describe recent progress in organ regeneration using various stem cell populations and strategies based on developmental biology and stem cell biology and discuss the future directions for organ replacement therapy as the generation of organ regenerative medicine
Studies of organ regeneration starting from bioengineering technology have made large strides towards the realization of organ regenerative therapy by incorporating the concepts from stem cell biology and developmental biology
Summary
Numerous advances in various research fields, including developmental biology, stem cell biology and tissue engineering technology, have facilitated regenerative medicine [1,2,3]. The generation of regenerative therapy targets entire organs composed of multiple cell types with a complex three-dimensional structure [14] In this decade, advances in the field of stem cell biology and developmental biology have provided new opportunities to regenerate functional organs. Functional organ regeneration was first achieved in 2007 by developing a novel cell manipulation method to generate a bioengineered organ germ with organ-inductive potential epithelial and mesenchymal stem cells isolated from an embryonic organ germ (figure 1b) [16]. We compartmentalized epithelial and mesenchymal cells isolated from the mouse embryo at a high cell density in a type I collagen gel to achieve a precise replication of the processes occurring during organogenesis Using this novel method, we have observed the functional regeneration of multiple types of ectodermal organs, such as teeth, hair follicles and secretory glands [17 –21]
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