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The Interstitium: Could We Be Looking at the Body's Third Circulatory System?

by Jessica Stavale

The Interstitium: Could We Be Looking at the Body's Third Circulatory System?

The Interstitium: Could We Be Looking at the Body's Third Circulatory System?

Could the relationship between fascia and the interstitium help explain some of the extraordinary changes we can experience in pain, movement, recovery, and even our physical appearance?

For years, I have challenged the way we traditionally look at the human body, particularly the tendency to examine muscles, nerves, organs, and individual symptoms as though they function independently. The more I have studied fascia and developed my work in Fascia Medicine™, the more convinced I have become that understanding the relationships between our tissues is essential to understanding how our bodies function, adapt, and respond to change.

One area of research that I find particularly fascinating involves the interstitium, an extensive network of fluid-filled spaces found within and between tissues throughout the body, including fascia. Scientists are investigating how these spaces participate in fluid movement, mechanical signaling, and biological communication, with some researchers exploring whether interconnected interstitial pathways might represent what could be considered a third circulatory system.

I believe this research may help us understand something I have observed repeatedly through The Fascia BluePrint Matrix: meaningful changes in one area of the body can sometimes be accompanied by improvements in entirely different areas, including changes in discomfort, tissue mobility, movement, and physical appearance.

My belief is that the interaction between fascia and the interstitium may be one of the reasons we can achieve such remarkable outcomes within the framework of The Fascia BluePrint Matrix. I believe we are influencing more than the mechanical properties of connective tissue alone, and understanding the relationship between its structural and fluid-containing components may help us explain some of the responses we observe.

Understanding the Interstitium and Its Relationship With Fascia

The interstitium refers to the spaces between cells and within connective tissues that contain interstitial fluid, extracellular matrix components, and various cells. These spaces participate in essential processes involving nutrient exchange, fluid balance, immune activity, and communication between cells and their surrounding environment.

In 2018, a team of scientists, including Dr. Petros Benias and Dr. Neil Theise, published groundbreaking research in Scientific Reports describing previously underappreciated fluid-filled spaces supported by collagen bundles throughout multiple tissues and organs.

Their findings were particularly significant because traditional methods of preparing tissue for microscopic examination could cause these spaces to collapse, making certain connective tissues appear more densely packed than they are in the living body. Through advanced imaging, the researchers were able to observe fluid-containing structures that had previously been difficult to appreciate.

This research expanded the conversation about connective tissue anatomy and raised important questions about how these spaces respond to mechanical forces, pressure, and fluid movement.

I find these discoveries especially relevant to fascia because connective tissue is not simply a collection of fibers holding our bodies together. It exists within a living environment containing fluid, cells, sensory structures, and extracellular matrix components that respond to the mechanical conditions we experience.

I believe part of fascia's extraordinary capabilities comes from its relationship with the interstitium. Fascia provides structural continuity and participates in force transmission and sensory signaling, while the interstitial environment contributes to fluid exchange and the conditions in which cells and connective tissue components function.

When I consider the outcomes we observe through The Fascia BluePrint Matrix, I believe this interaction deserves far greater attention. Changes in tissue mobility, pressure, and mechanical stimulation may involve multiple physiological responses, and the relationship between fascia and its fluid-containing environment could be an important part of that explanation.

Could the Interstitium Be the Body's Third Circulatory System?

The possibility of the interstitium representing a third circulatory pathway is being explored within scientific research, particularly through investigations into the continuity of fluid-filled spaces across anatomical boundaries.

We recognize the cardiovascular system for circulating blood and the lymphatic system for maintaining fluid balance, supporting immune activity, and returning excess interstitial fluid to the bloodstream. The interstitium is closely connected to these processes because interstitial fluid participates in the exchange of nutrients, signaling molecules, and other substances between blood vessels and surrounding tissues.

What researchers are continuing to investigate is whether larger interconnected interstitial spaces may provide additional pathways through which fluid and biological substances move throughout the body.

Scientists including Dr. Neil Theise have contributed important research to this discussion, examining the structure and continuity of these spaces and their potential implications for fluid transport, mechanical signaling, and biological communication.

The concept of a third circulatory system remains a scientific hypothesis rather than an established anatomical classification. However, I believe the possibility is compelling because it invites us to consider how fluid movement within connective tissues may influence the body's responses to mechanical forces.

This is particularly interesting when I consider the framework of The Fascia BluePrint Matrix. If fascia provides structural relationships across anatomical regions and the interstitium contributes to the fluid environment within those tissues, understanding their interaction may help us investigate why gentle, targeted mechanical work can sometimes be associated with changes beyond the immediate area being addressed.

I believe this relationship may eventually become an important part of explaining the outcomes we observe in pain, movement, recovery, and aesthetics.

The Tattoo Ink Study: Visible Evidence of Interstitial Spaces Within Fascia

One of the most fascinating studies supporting this evolving understanding was published in 2021 in Communications Biology, titled Evidence for Continuity of Interstitial Spaces Across Tissue and Organ Boundaries in Humans.

Researchers examined tissue samples containing tattoo pigment and identified particles beyond their original location in the skin, including within underlying subcutaneous fascia. The pigment was found both inside cells and within extracellular spaces between collagen bundles. Similar findings involving medically introduced pigment were observed in deeper tissues associated with the colon, including mesenteric fascia.

The scientists used these observations, along with additional anatomical evidence, to investigate whether interstitial spaces extend across tissue and organ boundaries. Their findings supported the possibility of continuity between certain interstitial compartments, although the precise contributions of fluid movement and cellular transport require further investigation.

What makes this research so compelling to me is that it allows us to visualize relationships within connective tissue that are otherwise difficult to observe.

The researchers have provided valuable evidence that the fluid-containing environment within fascia deserves much greater scientific attention.

I believe this is part of the missing piece in understanding why working with fascia can sometimes produce changes that extend beyond the area being addressed. The interstitium may contribute to the mechanical and physiological environment in which these responses occur, and understanding its relationship with fascia may eventually help us identify the mechanisms involved.

The tattoo pigment findings do not establish that fascia techniques move fluid through these pathways or explain outcomes. However, they provide a fascinating anatomical foundation for further investigation.

Original research figure


Figure 1: Tattoo pigment in interstitial spaces of the dermis and subcutaneous fascia

View the original scientific figure

Image credit: The authors of “Evidence for Continuity of Interstitial Spaces Across Tissue and Organ Boundaries in Humans,” Communications Biology (2021), Figure 1. DOI: 10.1038/s42003-021-01962-0. Licensed under Creative Commons Attribution 4.0. The original figure should be reproduced with its scientific labels, scale bars, and complete attribution.

Why I Believe This Relationship Helps Explain the Outcomes We See in Pain and Movement

One of the foundational principles I teach through The Fascia BluePrint Matrix is the importance of distinguishing between the location of pain and the potential source of contributing dysfunction.

Our bodies develop patterns of compensation, protective guarding, altered movement, and tissue restriction that can involve multiple anatomical regions. When we focus exclusively on the location of discomfort, we may overlook other relationships influencing how the body moves and responds.

The Fascia BluePrint Matrix was developed to help assess these relationships through five communication pathways and nine access points, allowing us to investigate patterns throughout the body rather than treating every symptom as an isolated problem.

Over the years, I have observed people experience meaningful improvements in discomfort and movement after working in areas that initially appeared unrelated to their primary concern. These experiences have continually encouraged me to investigate why the body responds as it does.

I believe the interaction between fascia and the interstitium may contribute to these outcomes. Fascia participates in mechanical force transmission and sensory signaling, while its fluid-containing environment contributes to tissue physiology and the conditions surrounding cells.

When tissue is gently lifted, mobilized, or exposed to rhythmic mechanical stimulation, multiple components of that environment may respond.

My hypothesis is that some of the changes we observe through The Fascia BluePrint Matrix involve the combined responses of fascia's structural network and its interstitial environment, rather than changes in connective tissue fibers alone.

This does not mean we have established that altered interstitial fluid flow is responsible for pain relief. Pain involves complex interactions between sensory signaling, the nervous system, inflammation, and many other factors. However, I believe the interstitium provides an important additional area of investigation that may help us develop a more complete understanding of these responses.

Why I Believe the Same Relationship Matters for Aesthetics

The relationship between fascia and the interstitium becomes especially interesting when we begin considering facial appearance, tissue mobility, and the changes people observe through fascia-focused aesthetic work.

Our facial appearance is influenced by multiple interacting structures, including skin, fat compartments, muscles, connective tissue, and the underlying skeletal framework. Fluid distribution, inflammation, tissue mobility, and age-related changes also contribute to how our faces look and feel.

Through The Fascia Aesthetic BluePrint Matrix, I teach people to look beyond individual wrinkles, jowls, or areas of facial tension and begin examining the relationships between the face, scalp, jaw, neck, chest, and other contributing regions.

This approach recognizes that the face is part of a larger anatomical and mechanical system.

I believe the relationship between fascia and the interstitium may help explain some of the visible changes people experience through this work, particularly when we consider the roles of tissue mobility, fluid balance, and mechanical forces in shaping the environment surrounding facial structures.

When we observe changes in facial puffiness, tissue movement, comfort, or the appearance of facial contours, I believe we should be investigating the combined responses of fascia and its interstitial environment.

The interstitium is not established as the mechanism responsible for facial lifting, wrinkle reduction, or lasting aesthetic changes from fascia techniques. However, understanding the interaction between connective tissue mechanics and fluid physiology may help researchers investigate why certain changes occur and how long they persist.

This is one of the reasons I believe the relationship between fascia and the interstitium is so important to the future of both functional and aesthetic fascia research.

The Fascia BluePrint Matrix: Understanding the Body Through Its Relationships

The Fascia BluePrint Matrix was developed around the understanding that the body functions through interconnected relationships rather than isolated anatomical structures.

Through its five communication pathways and nine access points, the Matrix provides a framework for examining how different regions may contribute to patterns of discomfort, restricted movement, postural changes, and tissue dysfunction.

My work involves observing tissue responses, assessing patterns, and using gentle techniques to explore how the body responds when mobility and mechanical conditions change.

The Stavale Method of Pull · Pulse · Push provides a structured way of applying these principles, with an emphasis on gentle tissue lifting, rhythmic movement, and supported integration.

I believe the interstitium adds an important dimension to understanding why these techniques may produce meaningful changes. When we interact with fascia, we are working with living tissue that contains extracellular fluid, sensory receptors, cells, and structural components that respond to mechanical forces.

I believe the outcomes we observe through the Matrix may reflect the combined responses of these interconnected components, including fascia and the interstitium.

This hypothesis is relevant across the areas I teach, from pain and movement to recovery and aesthetics, because each involves tissues responding to changing mechanical and physiological conditions.

My observations provide a reason to investigate these relationships, while controlled research is needed to establish which mechanisms are responsible for particular outcomes.

Why This Research May Change How We Understand the Human Body

A 2026 scientific review by Dr. Rebecca Wells and Dr. Neil Theise examines interstitial spaces across multiple anatomical scales, including larger connective tissue structures associated with fascia. Their work explores the potential roles of these spaces in mechanical signaling, biochemical communication, and possibly electrical signaling.

I believe this research is especially important because it encourages us to investigate relationships that traditional anatomical descriptions may not fully capture.

The body is continuously responding to movement, pressure, fluid exchange, and sensory information. These processes interact within tissues that are structurally and physiologically complex.

The more we understand how fascia and the interstitium influence one another, the greater our opportunity to investigate why the body responds to certain forms of movement and mechanical stimulation.

For me, this is directly relevant to the future of Fascia Medicine. I have spent years developing The Fascia BluePrint Matrix and observing changes that encourage me to look deeper into the relationships between connective tissue, sensory communication, and tissue function.

I believe the interaction between fascia and the interstitium may be one of the most important areas of research for understanding the outcomes we observe through this framework.

I am grateful for the scientists whose work continues to expand our understanding of these structures. Their discoveries provide an important foundation for the questions I am exploring and for the broader scientific investigation of connective tissue physiology.

A Missing Piece in Our Understanding of Human Health

The possibility that the interstitium represents a third circulatory pathway is fascinating, but I believe its relationship with fascia may ultimately prove even more important for understanding the human body.

When we begin examining fascia's structural and sensory roles alongside the fluid-containing environment of the interstitium, we gain a broader perspective on the biological relationships that may influence movement, discomfort, tissue health, and physical appearance.

I believe this combined understanding may help explain some of the remarkable outcomes I have observed through The Fascia BluePrint Matrix and The Fascia Aesthetic BluePrint Matrix. It may also provide new directions for research into pain, recovery, movement, and aesthetic changes.

My belief is that fascia and the interstitium, when studied together, will provide a significant missing piece in our understanding of the human body.

The scientists investigating these relationships deserve recognition for the discoveries that are moving this field forward. Their work allows us to ask increasingly meaningful questions about how our bodies function and how we might support health through a more complete understanding of our anatomy.

I intend to continue exploring these questions through observations within my framework, sharing emerging research, and encouraging people to understand their bodies through the relationships that connect them.

I believe we are only beginning to recognize what may be possible when we study fascia and the interstitium together.

A healthier you changes everything.

Scientific References

  1. Benias, P. C., et al. (2018). Structure and Distribution of an Unrecognized Interstitium in Human Tissues.Scientific Reports, 8, 4947. https://doi.org/10.1038/s41598-018-23062-6

  2. Evidence for Continuity of Interstitial Spaces Across Tissue and Organ Boundaries in Humans. (2021). Communications Biology, 4, 436. https://doi.org/10.1038/s42003-021-01962-0

  3. Ordner, J., et al. (2025). Continuity of Interstitial Spaces Within and Outside the Human Lung. Journal of Anatomy. https://doi.org/10.1111/joa.14280

  4. Wells, R. G., & Theise, N. D. (2026). Interstitial Spaces: A Basolateral Source of Structure and Signals. Annual Review of Cell and Developmental Biology. https://doi.org/10.1146/annurev-cellbio-111524-023144

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How My Work Evolved From Fascia Therapy Into Fascia Medicine Fascia therapy was an important part of the beginning of my work because working directly with the tissue allowed me to observe patterns again and again. I began noticing that the place someone experienced pain was not always the area that created the greatest change when we worked with it. I saw relationships between areas of the body that made me want to understand the pattern beyond the individual treatment technique. Those observations eventually became The Fascia BluePrint Matrix, built around five communication pathways and nine access points. I also developed the Stavale Scale of Dysfunction to give me a framework for assessing different levels of fascial dysfunction, while fascial posturing and the relationship between the cause site and pain site became additional pieces of the assessment process. This is where I make an important distinction between fascia therapy and Fascia Medicine. 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Choosing a Fascia Therapy Approach If you are exploring fascia therapy for yourself, I encourage you to understand the philosophy behind the method you are considering. Ask what the practitioner is assessing, how they determine where to work, what type of pressure or input they use and how they evaluate whether something changed. You can also pay attention to your own experience. How does your body move before the session? How does it move afterward? Did an area become less tender? Did the pulling change? Did you notice a difference somewhere other than the place that was directly treated? Those observations help you participate in the process instead of measuring the entire experience by how intense the treatment felt. There are also times when symptoms belong in a medical conversation. New or severe pain, significant swelling, unexplained bruising, numbness or weakness, difficulty breathing, chest pain, symptoms following a significant injury or other concerning or rapidly changing symptoms deserve appropriate medical evaluation. Recent surgery, pregnancy, injuries and medical conditions can also influence which forms of fascia therapy or self-treatment are appropriate for you. Understanding your body includes knowing when another form of support belongs in your care. Fascia Therapy Was the Beginning of a Much Larger Conversation My work began with my hands on the tissue and a desire to understand what I was feeling. Fascia therapy gave me a way to interact with the body, but the patterns I continued seeing pushed me to ask deeper questions. Why did working in one area change another? Why did two people with pain in the same location present so differently? Why did some areas continually return to the same pattern? Those questions changed the direction of my work. Fascia therapy became part of something larger: a way of understanding the body through communication, assessment, flow and connection. That evolution became Fascia Medicine. If you are just beginning to explore fascia, fascia therapy can be a beautiful introduction to becoming more aware of your tissue and movement. As your understanding grows, you can begin looking beyond the individual technique and learning how the relationships throughout the body create the larger picture. That is where the work continues for me today. Listen to the tissue.Restore your fascia. Change your life.A healthier, more connected you.

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