Interstitial Spaces: A Basolateral Source of Structure and Signals

Area of Science:

• Anatomy
• Physiology
• Extracellular Matrix Biology

Background:

• The mammalian interstitium, previously viewed as a simple space, is now recognized as a complex, body-wide network.
• Recent research reveals its presence at three interconnected scales: intercellular, pericapillary, and large interstitial spaces.
• These spaces, including fascia and vascular adventitia, are filled with hyaluronic acid and diverse extracellular matrices.

Purpose of the Study:

• To review how the multiscale anatomic concept of the interstitium reframes previous findings.
• To identify new research questions arising from the body-wide, multiscale nature of the interstitium.
• To explore the interstitium's role in fluid flow and as a signaling compartment.

Main Methods:

• Review of recent anatomical and physiological studies on the mammalian interstitium.
• Analysis of data concerning interstitial matrix composition and cell trafficking.
• Identification of emerging research questions based on the multiscale interstitial concept.

Main Results:

• The interstitium is a continuous, multiscale network throughout the body.
• Large interstitial spaces contain complex extracellular matrices supporting various signaling pathways.
• The interstitium acts as a significant compartment for soluble factor, mechanical, and electrical signaling.

Conclusions:

• The redefined concept of the interstitium necessitates re-examination of existing biological data.
• New avenues of research are opened regarding interstitial fluid dynamics and signaling.
• The interstitium is a dynamic and integral component of mammalian physiology.