Fascia is alive

How cells modulate the tonicity and architecture of fascial tissues

Robert Schleip, Heike Jäger and Werner Klingler

Cellular populations in fascia

Cells constitute only a minor portion of the volumetric quantity of fascial tissues. Nevertheless, they play a major role in modulating their architecture and stiffness. Among various cell-types the fibroblasts and sublineages are the most prominent cell-line in fascia. These cells are like nomadic construction workers, as well as cleaners and repair handymen, for the extracellular matrix. Their life span is estimated to be several months. In the past, metabolically active “fibroblasts” were distinguished from the less active “fibrocytes”. More contemporary texts, however, now tend to describe both forms as “fibroblasts”. Besides secreting precursors of most of the components of the extracellular matrix (a major exception being its large water content), and in secreting precursors for enzymes like collagenase that help in breaking these tissues down again, they also play important roles in tissue injury repair.

There are usually only a few immune cells like macrophages, a few mast cells, and some sporadic lymphocytes present in fascia. The mast cells contain granules rich in histamine and heparin, which play a key role in the inflammatory process. When activated, mast cells rapidly release these granules into the ground substance, activating blood flow and immune defense.

An often undervalued cell population within fascial tissues are univacuolar adipocytes. They are particularly abundant in areolar connective tissues, yet also in areas where fascial tissues frequently are engaged in shear and sliding motions. In addition, they are present in areas like the heel pad which are exposed to frequent pressure in addition to tensional loading. Here, the fat cells are arranged much more tightly and in smaller units than elsewhere, forming a most effective cushion. Although many people tend to regard these cells as less precious elements of their body, they fulfill important functions. This includes their recently discovered endocrinal functions: adipocytes are not only important producers of estrogen, but also of several other peptides and cytokines. Through these they influence appetite regulation, insulin/glucose regulation, angiogenesis, vasoconstriction, blood coagulation, and can even express proinflammatory conditions in the body. They are also one of the producers of the important cytokine transforming growth factor (TGF)-β, which we will address later. The detrimental effects of severe obesity on many physiological functions of the body are largely caused through several of these peptides and cytokines. On the other side, the common cosmetic surgery of liposuction can be expected to perturb local and global physiology and should therefore be considered with a degree of caution similar to a partial removal of other endocrine organs in the body. The humoral factors are transmitted to and from the adipocytes via the bloodstream. Fat tissue is well vascularized, especially below the superficial fascial layer. Therefore, another portion of cells in fascia make vascular, lymphatic and neural tracts, however small those vessels may be.

Fascial tonicity

In an examination of human lumbar fascia, a group of biomechanical investigators around Yahia et al. (1993) discovered its ability for tissue contraction. Three years later, the German anatomy professor Staubesand, in an examination of the human fascia profunda of the lower leg, documented the presence of smooth muscle-like cells (Staubesand & Li 1996). As he also found a rich presence of sympathetic nerve fibers in their vicinity, he postulated a potential close connection between sympathetic activation and fascial tonus regulation. Indeed, many clinicians report a frequent association between long-term psychological stress and a perceived increase in palpatory myofascial stiffness. Such increase in tissue stiffness seems to be present also at rest, a condition for which most electromyography experts agree that most skeletal muscles are electrically silent (Basmajian & DeLuca 1985). It has therefore been suggested that human resting muscle tone may be significantly influenced by changes in fascial stiffness (Masi & Hannon 2008).

This was the background for the authors’ research group to provide a more thorough examination of human fasciae for the presence of contractile cells. In a collection of biopsy tissues – taken from human lumbar fascia, iliotibial tract, interspinous ligament and plantar fascia – immunohistochemical staining for the presence of α-smooth muscle actin (ASMA) stress fiber bundles was performed. Such staining is commonly used to identify the presence of cells with smooth muscle-like contractile features. Subsequent microscopic analysis then revealed that some of the stained cells could be identified as smooth muscle cells, which were then involved with the formation of blood vessels. The remaining cells were myofibroblasts, a type of connective tissue cells whose presence in fascia had previously been reported only from wound healing or pathological tissue contractures. These highly contractile cells – generally considered as a special phenotype of fibroblasts – were found in all tissue samples, although with very large density variations.

Unexpectedly, it was also revealed that the intramuscular perimysium seemed to express a higher density of myofibroblasts than the endomysium, perimysium, or fascia profunda. Interestingly, meat scientists report that tonic muscles tend to contain a thicker perimysium, giving them the appearance of tough meat (in contrast to the tender meat quality of phasic muscles, which have a much thinner perimysium; Borg & Caulfield 1980). It has therefore been suggested that the augmented resting stiffness of some tonic muscles could be related to an enhanced myofibroblast density in their perimysium (Schleip et al. 2006b).

In some tissue samples of the lumbar fascia a dramatically increased density of myofibroblasts was found. Density was then comparable to that reported in Dupuytren contracture or frozen lumbars. This could suggest that the lumbar fascia may sometimes express a pathological condition similar to those two common fascial tissue contractures (Fig. 4.2.1).

Fig. 4.2.1 • Indications for fascial pathology of “frozen lumbar”? Section of the posterior layer of the lumbar fascia at the level of L2. Note the high density of myofibroblasts, which in this patient is comparable to their reported density in the shoulder capsule during a “frozen shoulder” pathology. This suggests that, at least in this patient, the low back region could be affected by fascial contracture and stiffening similar to that of a “frozen shoulder”. Arrows indicate examples of stress fiber bundles containing α-smooth muscle actin (a differential marker for myofibroblasts), which are stained here in dark gray. Length of image 225 μm. Adapted from Schleip et al., 2006a, with permission.

It has been proposed that a tendency for high myofascial stiffness might be a polygenic human trait, being associated with a predisposition for living in colder climates (Masi & Hannon 2008). This is supported by the high prevalence of ankylosing spondylitis and Dupuytren contracture in people with a Northern European ancestry line. On the other hand, the condition of general joint hypermobility is more frequently expressed in people from Africa and Southern Asia. It has therefore been suggested that general joint mobility (and tissue stiffness) could be influenced by myofibroblast density in muscular fasciae (Remvig et al. 2007). This would be congruent with the finding that hypermobile people tend to have a slower wound contracture and reduced scar formation, whereas people with “Vikings’ disease” (i.e., Dupuytren contracture) tend to have faster wound contracture, are more prone to scarring, and are also more often affected by other myofibroblast-driven fascial contractures, such as frozen shoulder or plantar fibromatosis (Hart & Hooper 2005).

From myofibroblast contraction to tissue contractures

It is assumed that most myofibroblasts develop out of regular fibroblasts. This transition is stimulated by an increase in mechanical strain, as well as by specific cytokines Figure 4.2.2. Myofibroblasts play an important role during wound healing, and are also involved in many pathological fascial contractures (such as Peyronie’s disease, hypertrophic scar, plantar fibromatosis, Dupuytren contracture, or frozen shoulder). Due to their possession of dense ASMA stress fiber bundles, their contractile capacity is four times stronger than regular fibroblasts.