Abstract
When Clifford Grobstein set out to study the inductive interaction between tissues in the developing embryo, he developed a method that remained important for the study of renal development until now. From the late 1950s on, in vitro cultivation of the metanephric kidney became a standard method. It provided an artificial environment that served as an open platform to study organogenesis. This review provides an introduction to the technique of organ culture, describes how the Grobstein assay and its variants have been used to study aspects of mesenchymal induction, and describes the search for natural and chemical inducers of the metanephric mesenchyme. The review also focuses on renal development, starting with ectopic budding of the ureteric bud, ureteric bud branching, and the generation of the nephron and presents the search for stem cells and renal progenitor cells that contribute to specific structures and tissues during renal development. It also presents the current use of Grobstein assay and its modifications in regenerative medicine and tissue engineering today. Together, this review highlights the importance of ex vivo kidney studies as a way to acquire new knowledge, which in the future can and will be implemented for developmental biology and regenerative medicine applications.
Highlights
Kidneys develop from a subregion of the embryonic mesodermal tissue, the intermediate mesoderm that generates two key cell types, the epithelial—ureteric bud (UB), and the mesenchymal—metanephric mesenchyme (MM)
As a relatively simple and cheap method, it provided a platform that could be changed to fit the needs of novel ideas
Questions of mesenchymal induction and competence have been explored. Tissues, such as the embryonic spinal cord or the salivary gland that can act as natural inducers and chemical inducers, such as lithium and CHIR99021, of the metanephric mesenchyme have been defined
Summary
Kidneys develop from a subregion of the embryonic mesodermal tissue, the intermediate mesoderm that generates two key cell types, the epithelial—ureteric bud (UB), and the mesenchymal—metanephric mesenchyme (MM). The nephron is composed of the renal corpuscle—the glomerulus, the proximal tubule, the Loop of Henle, and the distal tubule. The latter connects the nephron to the collecting duct system. To study the cellular mechanisms of organ development, scientists have been culturing organs since the early 1930s, using methods such as hanging drops or watch-glass cultures [1]. The “father of kidney organ culture,” Clifford Grobstein, developed the basic method to investigate kidney tubule induction. Provide a brief, yet inclusive, summary of the progress in the field of kidney developmental biology that is based on the ex vivo/in vitro kidney culture model
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