A New Perspective on Fibrosis: The Role of the Interstitium in Human Physiology and Disease

The concept of a unified, continuous interstitium across tissues and organs as proposed by Neil Theise and his colleagues in their landmark studies (Benias et al., 2018; Theise et al., 2018) provides an expanded perspective on the fascial system, its role in human physiology, and its implications in various pathological conditions, including fibrosis.

According to their work, the interstitium is an interconnected, fluid-filled space existing within and between tissues, covered by a layer of fibroblast-like cells and supported by a scaffold of thick collagen bundles. This newly appreciated anatomical structure forms a fluid conduit, which interconnects different parts of the body and may play a crucial role in fluid dynamics, cell migration, and even the spread of disease.

Applying these insights to fibrosis and the “walling off” process presents intriguing new perspectives. Traditionally, fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) proteins, such as collagen, leading to the disruption of normal tissue architecture and function. Within the context of a continuous interstitium, fibrosis can be perceived as a more systemic event, potentially disrupting large-scale fluid dynamics and affecting the distribution and drainage of substances throughout the body.

In this larger network, the process of fibroblast encapsulation of foreign particles or harmful substances can be envisioned as a defense mechanism, mitigating systemic dissemination of potentially harmful agents. The encapsulated substances, suspended within the continuous interstitium, could potentially alter the composition and function of the interstitial fluid, exerting more widespread effects than previously assumed.

Furthermore, the fibrotic remodeling of the interstitial collagen bundles could directly impede the flow of interstitial fluid. This mechanical obstruction could exacerbate the accumulation of metabolic waste products and toxins, creating a vicious cycle of local inflammation, fibroblast activation, and further fibrosis.

However, this novel view of the interstitium also invites further investigation into therapeutic opportunities. Could targeted interventions to ‘decongest’ the interstitium, possibly through methods such as mechanical vibration therapy, help mitigate the systemic impacts of fibrosis? Could enhancing the lymphatic clearance of the interstitial fluid offer a means to manage fibrotic diseases?

The concept of the interstitium as a unified, fluid-filled space within and across tissues and organs offers new avenues for research into many pathological conditions, including fibrosis. As our understanding of these structures continues to evolve, it will undoubtedly reshape our view of human physiology and pathology.

References

Benias, P. C., Wells, R. G., Sackey-Aboagye, B., Klavan, H., Reidy, J., Buonocore, D., … & Theise, N. D. (2018). Structure and Distribution of an Unrecognized Interstitium in Human Tissues. Scientific Reports, 8(1), 4947.

Theise, N. D., & Harris, R. (2018). Postmodern Biology: (Adult) (Stem) Cells Are Plastic, Stochastic, Complex, and Uncertain. Handbook of experimental pharmacology, 260, 389-408.

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