Kidney  - Development and Stem Cells

Anatomical Structure and Function of the Kidney:

The kidneys are part of the urogenital system and are responsible for modulating a variety of complex physiologic and homeostatic processes. The kidney's main function is to regulate the composition and volume of the body fluids, and to eliminate metabolic waste products. This is accomplished via blood filtration through the nephron, the functional unit of the kidney, which has a characteristic segmental organization. In addition to excretion of waste products, the kidneys are also responsible for endocrine functions, regulation of blood pressure and maintenance of acid–base balance.

Each kidney is comprised of a fibrous outer layer called the renal capsule, a peripheral layer called the cortex, and an inner layer called the medulla. The medulla is arranged in multiple pyramidal structures that, together with the overlying cortex, comprise a renal lobe. The papilla, tip of each pyramid, drains urine into minor and major calices that empty into the renal pelvis. There, the urine is transmitted through the ureter to the bladder. The kidney is a highly complex organ, with over 30 different types of cells.

Embryonic Development of the Kidney: 

Three pairs of kidneys successively form within the intermediate mesoderm: pronephros, mesonephros and metanephros. The pronephros and mesonephros are transient structures, and only the metanephros remains as the functional kidney of the newborn. The metanephros is characterized by its branched collecting duct system and large number of nephrons (∼11,000 in the mouse and ∼1 million in humans).

The metanephros develops through a complex set of reciprocal interactions between the metanephric mesenchyme (MM) and the Wolffian duct (nephric duct), which is derived from the intermediate mesoderm. The MM secretes GDNF, which upon binding to the c-RET receptor, induces outgrowth of ureteric buds (UB) from the nephric duct.  The UBs then invades the MM. Mesenchymal cells condense to form condensed (cap) mesenchyme (CM) around each UB, a subset of cells which give rise to nephron progenitors. The ureteric bud is thereupon induced to branch. The CM proximal to the UB tips condenses to form pretubular aggregates, which undergo a mesenchymal-to-epithelial (MET) transformation and form epithelial structures called renal vesicles. During tubulogenesis, the more complex epithelial comma- and S-shaped bodies are formed. During nephron maturation, S-shaped bodies form most of the mature nephron and fuse to UB derivatives, which become collecting ducts. During this process, endothelial cells migrate to form the glomerulus, which is the network of blood capillaries in the cup-like end (Bowman’s capsule) of the nephron.  There, waste products are filtered from the blood into the kidney epithelial tubule. Tubule elongation, including patterning and segmentation, proceeds to form the mature nephron compartmentalized into the proximal tubule, loop of Henle and distal tubule.