Interstitial cells are a diverse category of cells located in the interstitium, the spaces between the functional cells of an organ. They are found in the connective tissue that supports organs throughout the body. The specific nature and function of these cells vary dramatically depending on their location, acting as either supportive or functional units integral to the tissue they inhabit.
The Interstitium Network
The interstitium is a body-wide network of fluid-filled spaces found within and between tissues. This network is supported by a flexible lattice of collagen proteins, creating a honeycomb-like structure. The fluid within these spaces, known as interstitial fluid, is a reservoir and transportation system for nutrients, solutes, and signaling molecules that are distributed among organs, cells, and capillaries.
In 2018, research proposed that the interstitium could be considered a distinct organ, a perspective that highlights its interconnected nature. This view was made possible by new imaging technology that allowed scientists to observe these fluid-filled spaces in living tissue for the first time. Previously, standard methods for preparing tissue for microscopic examination involved draining away fluid, which caused the interstitial spaces to collapse, making them appear as dense, solid tissue.
This network structure has significant functional implications. It acts as a shock absorber, protecting organs and muscles from tearing as the body moves, pumps, and pulses. The interstitium also drains directly into the lymphatic system, making it a pathway for immune cells. The recognition of the interstitium as a connected system provides a new framework for understanding how processes like inflammation and disease can spread from one part of the body to another.
Key Types and Their Specialized Roles
Interstitial Cells of Cajal (ICCs)
Located within the muscle walls of the gastrointestinal tract, Interstitial Cells of Cajal (ICCs) are the “pacemaker” cells of the gut. These specialized cells generate and propagate the electrical slow waves that trigger the rhythmic contractions of the digestive system, a process known as peristalsis. ICCs form a network that is electrically coupled with the smooth muscle cells, ensuring that these contractions are organized and effective.
The function of ICCs is deeply integrated with the enteric nervous system, the gut’s own intrinsic nervous system. ICCs act as intermediaries, translating signals from enteric neurons into responses in the smooth muscle cells. A disruption in the health or density of the ICC network can lead to significant motility disorders. Changes in these cells are also linked to the development of certain tumors, most notably gastrointestinal stromal tumors (GISTs), which often originate from ICCs.
Leydig Cells
Leydig cells are found in the testes, in the interstitial tissue adjacent to the seminiferous tubules where sperm production occurs. Their primary function is the production of testosterone and other androgens, or male sex hormones. This process is stimulated by luteinizing hormone (LH) from the pituitary gland. When LH binds to receptors on the Leydig cells, it initiates a signaling cascade that results in the synthesis and secretion of testosterone.
Testosterone produced by Leydig cells is necessary for male reproductive health, including the development of secondary sexual characteristics, muscle mass, and bone density. The cells themselves are polyhedral and contain a large amount of smooth endoplasmic reticulum, an organelle central to the production of steroid hormones. While prominent in males, a similar type of cell is also found in the ovaries and contributes to androgen production in females.
Renal Interstitial Cells
Within the kidneys, a specific population of interstitial cells plays a direct role in regulating the body’s oxygen levels. These renal interstitial fibroblasts are the primary producers of erythropoietin (EPO), a hormone that stimulates the bone marrow to produce red blood cells. When the body detects low oxygen levels (hypoxia), these cells increase their production of EPO to boost the oxygen-carrying capacity of the blood.
These fibroblast-like cells are located in the cortex and outer medulla of the kidney. Under certain conditions, such as anemia-induced low blood pressure, these same cells can also be prompted to produce renin, a substance involved in regulating blood pressure. This dual capability highlights their function as regulators of the body’s circulatory and oxygen-delivery systems.
General Pathological Roles
When tissues and organs are subjected to chronic injury or inflammation, interstitial cells can play a part in the development of disease. One of the most significant pathological processes involving these cells is fibrosis, the formation of excessive scar tissue. In a healthy response to injury, fibroblasts produce a moderate amount of extracellular matrix proteins, such as collagen, to repair damage.
In diseases affecting organs like the kidneys, liver, and lungs, this healing process can become dysregulated. Interstitial cells, particularly fibroblasts, can transform into a more active state, becoming myofibroblasts. These activated cells produce large amounts of collagen and other matrix components, leading to the progressive stiffening and scarring of the organ. This fibrotic tissue replaces functional tissue, which can impair organ function and ultimately lead to organ failure. For instance, in chronic kidney disease, renal interstitial cells that normally produce EPO can transform into myofibroblasts, contributing to both fibrosis and the anemia characteristic of the disease.
The interstitium’s function in fluid regulation also means that dysfunction can contribute to edema, the swelling caused by excess fluid trapped in the body’s tissues. The balance of fluid between blood vessels and the interstitial space is maintained by an interplay of pressures. If this balance is disrupted, for example by increased pressure in the capillaries or damage to the vessel walls, fluid can accumulate in the interstitium. Because interstitial cells are part of this fluid-filled environment, their responses to inflammation or injury can influence capillary permeability and the local pressure gradients that lead to edema.