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66 Toldt’s fascia
one such species, and the development of this as a model sys-
tem, represents an area of future research in this fi ld.
e lack of representative animal models is in itself
informative. It is possible that attachment of the mesentery
to the posterior abdominal wall may well be anatomi-
cally exclusive to H. sapiens and other higher order species
(i.e.,apes). Absence of attachments, would mean that aer
standing upright, the entire gastromesenteric complex would
collapse into the pelvis, and function would be impaired.
SURGICAL IMPLICATIONS
OF TOLDT’S FASCIA
Toldt’s fascia is of crucial technical importance in resectional
colorectal surgery. Together with the mesocolon (or colon), it
generates an interface that must be disrupted in order to free
these structures from the posterior abdominal wall and allow
their resection (Figure 5.9). It thus contributes an anatomic
roadmap that is of fundamental importance in safe surgery.
Digression from this anatomic roadmap into the retroperito-
neum is associated with damage to ureters, gonadal vessels, and
duodenum. Digression from the roadmap into the mesentery is
associated with damage to the latter and extensive hemorrhage.
By adhering to the planar roadmap provided by the fascia, sur-
geons achieve a mesenteric and intestinal resection with mini-
mal blood loss or tissue damage in general [1,2,24,30–34].
TOLDT’S FASCIA AND RADIOLOGIC
IMPLICATIONS
e anatomic properties of the fascia render it dicult to
visualize out with the surgical context. Even intraoper atively,
it can be dicult to visualize because it is translucent and
inmany regions extremely thin (Figures 5.3, 5.4, and 5.9).
Notsurprisingly, the fascia is dicult to visualize in radio-
logic contexts, unless it is thickened due to a pathologic
process (Figure 5.8). Recent advances in radiologic inter-
pretation of computerized tomographic imaging have led
to increased rates of identifi ation of the fascia [35]. Th s
is dealt with in greater detail in Chapter 8. In keeping with
this, what was previously referred to as the “anterior parare-
nal fascia” is now increasingly recognized as representing a
region of Toldt’s fascia[35].
e development of the Visual Human Project (VHP)
is also likely to further improve our understanding of the
fascia [36]. In the VHP, a full color dataset enables one look
at subtle structures in their undisturbed and insitu format.
is represents an exciting opportunity, and it is through
the identication of undisturbed fascial layers that we are
likely to better understand the relationship between Toldt’s
fascia, the overlying mesenteric organ, and associated peri-
toneal reections [35,36].
ADHESIONS AND TOLDT’S FASCIA
ere is a striking similarity between adhesions and Toldt’s
fascia. Just as the fascia can be lmy or areolar in appear-
ance, so too can adhesions. is similarity points to an
overlap in the cellular and molecular processes involved in
formation of both. Considered in this manner, it is feasible
that adhesion formation is not a pathologic process per se,
but rather a fundamentally important embryologic process
that ensures attachment and normal function of the gastro-
mesenteric complex.
Fascia and related structures
Ureter
Gonada
l
vein
T
oldt’s
fascia
Figure 5.9 Intraoperative photomicrograph demonstrating the glistening fascia with the ureter and gonadal vessels
located immediately underneath Toldt’s fascia.
References 67
FUTURE DIRECTIONS
Experimental and clinical interest in the composition and
distribution of Toldt’s fascia is increasing. e absence of an
animal model in which the mesentery has attached to the
posterior abdominal wall has been discussed and deserves
particular emphasis. Currently, eorts are focused at arti-
cially stimulating fascial development in the rodent or por-
cine context by suturing mesentery to the retroperitoneum.
e identication of lymphatic vessels in the fascia
prompts further investigation of this. In general, opera-
tive surgery involves leaving the fascia behind. However,
malignant cells are known to utilize lymphatic channels in
spreading from a primary tumor. e question thus arises
as to whether the fascia should also be resected or not. e
origin and termination of fascial lymphatics should be
determined to partly address this question.
SUMMARY
Toldt’s fascia is continuous from the root region of the mes-
entery at the superior mesenteric artery, to the anorectal
junction, where it both expands and condenses to form
Waldeyer’s fascia. Th s continuity is disrupted only at the
peritoneal refl ctions, the zones of adherence in the pel-
vis, and where major vessels enter or leave the mesentery.
e right mesocolic fascia, the left mesocolic fascia, and the
mesosigmoidal and mesorectal fascia are dierent regions
of the same contiguous structure. Macroscopically, it resem-
bles adhesions that may arise aer abdominal surgery.
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observational study. Colorectal Dis, 2012. 14(4):
421–428; discussion 428–430.
2. Culligan, K. etal., The mesocolon: A histological
and electron microscopic characterization of the
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7. Chebbi, F. etal., Laparoscopic ileo-cecal resection:
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18. Coffey, J.C. etal., Terminology and nomencla-
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mesenteric anatomy. Tech Coloproctol, 2014. 18(9):
789–794.
19. Sehgal, R. and J.C. Coffey, Historical develop-
ment of mesenteric anatomy provides a universally
applicable anatomic paradigm for complete/total
mesocolic excision. Gastroenterol Rep, 2014. 2(4):
245–250.
20. Thorek, P., C.T. Linden, and N. Swan, Anatomy
inSurgery. Springer, New York, 2012, pp.
457–506.
21. Treves, F., Lectures on the anatomy of the intesti-
nal canal and peritoneum in man. Br Med J, 1885.
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Springer, New York, 2006, pp. 66, 68, 155, 156, 161,
173–175, 177, 185, 250, 291, 293, 329.
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Health, Philadelphia, PA, 2013, pp. 31, 36, 55, 79, 80,
100, 147, 160, 183, 191, 197, 221.
68 Toldt’s fascia
24. Culligan, K. etal., A detailed appraisal of mesocolic
lymphangiology—An immunohistochemical and ste-
reological analysis. J Anat, 2014. 225(4): 463–472.
25. Adams, S.D. and M.P. Stanton, Malrotation and intes-
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CTMR, 2014. 35(6): 555–570.
27. Tackett, J.J., E.D. Muise, and R.A. Cowles,
Malrotation: Current strategies navigating the
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28. Ballesteros Gomiz, E. etal., Intestinal malrotation—
Volvulus: Imaging ndings. Radiologia, 2015. 57(1):
9–21.
29. diZerega, G., Peritoneal Surgery. Springer, New York,
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30. Li, L.J. etal., Progress in laparoscopic anatomy
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31. Okazaki, T. etal., Toldt’s fascia ap: A new technique
for repairing large diaphragmatic hernias. Pediatr
Surg Int, 2005. 21(1): 6 4 –67.
32. Sehgal, R. and J.C. Coffey, The development of
consensus for complete mesocolic excision (CME)
should commence with standardisation of anatomy and
related terminology. Int J Colorectal Dis, 2014. 29(6):
763–764.
33. Coffey, J.C. and P. Dockery, Colorectal cancer:
Surgery for colorectal cancer—Standardization
required. Nat Rev Gastroenterol Hepatol, 2016.
13(5): 256–257.
34. Zhang, C. etal., Perirectal fascia and
spaces:Annulardistribution pattern around the
mesorectum.DisColon Rectum, 2010. 53(9):
1315–1322.
35. Coffey, J.C. etal., An appraisal of the computed
axial tomographic appearance of the human
mesentery based on mesenteric contiguity from
the duodenojejunal exure to the mesorectal
level.EurRadiol, 2016. 26(3): 714–721.
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69
6
Mesenteric physiology
J. CALVIN COFFEY, RISHABH SEHGAL, AWAD M. JARRAR, AND MATTIAS SOOP
Form follows function.
Louis Sullivan
AIM
is chapter will discuss evidence supporting the sugges-
tion that the mesentery is ideally positioned to sample sig-
nals and regulate systemic and local activities in response
to these.
INTRODUCTION
In the past, it was thought the sole function of the mesentery
was to provide a scaff ld within which blood vessels could
pass to and from the gastrointestinal tract [1–7]. While
this is partially correct, additional functions have become
apparent and led to an increase in research in mesenteric
physiology. e data from which to draw on for this sub-
ject are considerable and beyond the scope of a summative
review such as this. However, the key points and supportive
information can be emphasized. Perhaps most importantly,
the histologic contiguity that exists between the intestine,
mesentery, and body proper means that the mesentery
occupies a unique anatomic position (Figure 6.1) [6–10]. It
is interposed between the intestine and body proper and
thus optimally positioned to orchestrate systemic responses
to environmental cues (and vice versa) (Figure 6.1) [3,9,10].
is chapter will demonstrate that the mesentery is not
merely a bystander in homeostasis but that it plays a central
role across a range of processes.
VISCERAL ADIPOSITY
e past two decades have seen increasing recognition of
the importance of visceral adiposity in regulating a range
of homeostatic processes within the body [11–21]. Visceral
adiposity is a collective term for adipose tissue whose venous
return is through the portal and not the systemic circula-
tion (i.e., greater omentum, small bowel mesentery, and
retroperitoneum) (Table 6.1) [22–36]. Many argue that fat
in and surrounding abdominal viscera should be included
in the term. Even to the present, however, it is rare for the
mesocolon to be included in appraisals of visceral adiposity.
As we now acknowledge that the mesocolon is a substan-
tive entity, spanning the small and large bowel, it follows it
should also be included in the term (Figure 6.2) [37]. When
visceral adiposity is considered in this manner, it is readily
apparent that the mesenteric component is the largest.
Table 6.1 summarizes the activities associated with dif-
ferent fat depots including those contributing to visceral
adiposity. In keeping with trends to date, the mesocolon
is not included. It is imperative that the adipose activities
listed should be characterized within the mesocolon. is
represents an avenue for future research.
In an intriguing article entitled “Is visceral adiposity
the enemy within,” Tracy etal. argued in support of links
Aim 69
Introduction 69
Visceral adiposity 69
Mesenteric cytokine production 70
Mesenteric production ofC-reactive protein 70
Migration during embryologic development 70
Mesentery as a regulatory hub 71
Mesenteric mesothelial plasticity 74
Mesenteric mesothelial plasticity and intra-abdominal
pathology 74
Mesothelial secretion and absorption of peritoneal uid 75
Mesothelial lymphatics 76
Greater omentum 76
Future studies 79
Summary 79
References 79
70 Mesenteric physiology
between visceral adiposity and homeostatic processes
suchinammation, brinolysis, and coagulation [38]. ey
demonstrated how numerous diseases result from derange-
ments in these and other activities. e association between
visceral adiposity and homoeostasis then led to the sug-
gestion that variations in visceral adiposity themselves
contribute to disease development. Indeed, population-
based studies examining the correlation between visceral
adiposity and the development of atherosclerosis support
this argument [38–44]. Increases in visceral adiposity have
recently been associated with atherogenic dyslipidemia,
metabolic syndrome, and diabetes [45–51]. Future studies
should examine if mesenteric and mesocolic components
of visceral adiposity contribute in a diffe ential manner to
disease development.
MESENTERIC CYTOKINE PRODUCTION
e mesentery is a major source of cytokine production.
e list of mesenteric cytokines is increasing and pres-
ently includes adipophilin, perilipin, resistin, and leptin
(Table 6.2) [16,52–54]. Alterations in the production of
these have also been linked to metabolic syndrome, ath-
erosclerosis, and diabetes. ese associations point to roles
for mesenteric cytokines in glycemic and lipid regulation in
general. Most studies examining visceral adiposity-associ-
ated cytokine production focus on outputs from the greater
omentum and small intestine [29,55–57]. e mesocolon
has been largely excluded from these evaluations. Given
similarities in embryologic origin, adipose composition
and venous return (i.e., through the portal system), it is
reasonable to suggest that separate mesocolic regions also
produce cytokines. It is important to investigate this sug-
gestion at all mesocolic levels.
Data suggest that in Crohn’s disease, mesenteric cyto-
kine production diers between inamed and noninamed
mesentery. In Crohn’s disease, mesenteric abnormalities
appear to precede and drive mucosal and gastrointestinal
abnormalities [58–73]. As Crohn’s is thought to involve
environmental factors (i.e., bacteria) within the gutlumen,
these observations indicate that mesenteric cytokine pro-
duction is inuenced by gastrointestinal bacteria. More-
over, it suggests that mesenteric cytokine production plays
a role in intestinal inammation and derangements thereof
[59,61,74–80].
MESENTERIC PRODUCTION
OFC-REACTIVE PROTEIN
C-reactive protein (CRP) is an acute phase protein that
will be considered separately given recent ndings [81]. In
the past, the liver was regarded as the main source of CRP.
e mesentery has recently emerged as a further, though
somewhat unexpected, source. In a landmark study,
Peyrin-Biroulet showed that mesenteric (and not hepatic)
production of CRP is a major determinant of systemic
CRP in patients with Crohn’s disease [69].
Amato et al. noted a correlation between visceral
adiposity, increased systematic CRP, and the development
of diabetes [20,45,82]. In the non-overweight obese, visceral
fat is signicantly increased compared with subcutaneous
fat [83–85]. is imbalance is linked with alterations in
CRP that correlate with abnormalities in insulin resistance
[85–90]. us, it would appear that ratios between diffe -
ent fat depots inuence systemic CRP and glycemic con-
trol. is observation, if it holds, could have far-reaching
implications.
MIGRATION DURING EMBRYOLOGIC
DEVELOPMENT
Increasing data suggest that the mesentery provides a
platform along which several cell types migrate during
embryogenesis, to reach the intestine. Support for this
comes from observations of connective tissue and vascu-
lar continuity between the intestine and the mesentery.
Nishiyama et al., in Nature Neuroscience 2012, demon-
strated a remarkable cellular journey made by neural crest
cells as these migrate through the dorsal mesentery to reach
the intestine. Once they reach the intestine, they migrate
along its longitudinal axis to populate the entire enteric
nervous system (Figure 6.3) [91]. While Nishiyama’s paper
demonstrated the importance of the mesenteric scaff ld
for cellular migration, it could also explain the develop-
ment of gastromesenteric neuroendocrine abnormalities.
Neuroendocrine tumors are thought to arise from neural
crest cells [92]. Itisfeasible thataltered migration of neural
Mesenteric
connective
tissue
Intestinal
connective
tissue
Mesenteric and intestinal continuity
Figure 6.1 2.5D snapshot of a 3D digital model demon-
strating the mesentery and adjacent intestine. The layers
of the intestine are demonstrated. Contiguity occurs in
the connective tissue between the mesentery and adja-
cent intestine.
Mesentery as a regulatory hub 71
crest cells through the mesentery and intestine predisposes
to mesenteric neuroendocrine tumors later in adult life.
MESENTERY AS A REGULATORY HUB
Emerging evidence suggests that intestinal bacteria regulate
mesenteric events and that these in turn control immuno-
logic responses within adjacent intestine. Derangements
along this immunologic axis are increasingly thought to
occur in inammatory bowel disease and could also play a
greater role in several forms of gastrointestinal inamma-
tion [93–97]. Increasingly, the mesentery is being viewed
as a regulatory hub, or signal box, and that this function is
played out on a connective tissue platform, into which adi-
pocyte, mesenchymal, and immunologic cells feed molecu-
lar contributions.
Table 6.1 Properties of various white adipose tissue depots in nonobese and obese humans
Study Year Journal Variable Nonobese Obese Reference
Fried
etal.
1993 J Clin Invest Adipocyte size Not determined Smaller in OM fat than
SAT in women
[27]
Kraunsøe
etal.
2010 J Physiol Mitochondrial
number and
respiration rate
Not determined Greater mitochondria
+ higher respiration
rates in OM vs. SAT
[33]
Hoffstedt
etal.
1997 J Lipid Res Lipolysis rate No differences
between OM and
SAT adipocytes
Higher in OM vs. SAT [31]
Ray etal. 2009 Lipids Health
Dis
Basal and
NA-induced
lipolysis in
adipocytes
Not determined Lower in OM [35]
Ray etal. 2010 Lipids Health
Dis
HSL mRNA and
protein levels
mRNA expression
lower in OM fat vs.
SAT
Similar as in lean
subjects; in both
depots mRNA 3×
higher than in lean
women
[35]
Ray etal. 2011 Lipids Health
Dis
Perilipin mRNA and
protein levels
mRNA expression
similar in OM fat vs.
SAT; 2× higher
protein level in OM
fat vs. SAT
2× lower mRNA level
in OM fat vs. SAT;
similar protein level
in both fat locations
[35]
Bonen
etal.
2006 Int J Obes Fatty acid
transporter
Higher by 50% in VS
vs. SAT
Similar in VS and SAT
depots
[28]
FAT/CD36 protein
expression
Hou etal. 2009 Obesity Lipogenesis: DGAT
activity
2× higher in OM fat
vs. SAT
Similar in OM fat and
SAT
[32]
Virtanen
etal.
2002 J Clin
Endocrinol
Metab
Insulin-stimulated
glucose uptake
Higher in VS vs. SAT Similar as in nonobese
men
[36]
Drolet
etal.
2009 Obesity Adiponectin release
by isolated
adipocytes
Similar in OM and SAT Reduced in OM and
unchanged in SAT
fat
[29]
Ortega
etal.
2009 Obesity Expression of
thyroid hormone
receptors
Similar in OM and SAT TRα and TRα1 mRNA
increased in SAT vs.
OM fat
[34]
Erman
etal.
2011 Int J Obes Expression of
growth hormone
receptor
Higher GHR mRNA
levels in OM fat than
in SAT
Lower GHR mRNA in
OM fat and SAT
than in lean subjects
[30]
Abbreviations: DGAT, diacylglycerol acyltransferase; FAT/CD36, fatty acid transporter/cluster of differentiation 36; GHR, growth hormone
receptor; HSL, hormone-sensitive lipase; NA, noradrenaline; OM, omental; SAT, subcutaneous adipose tissue; TRα, thyroid receptor α;
VS, visceral.
72 Mesenteric physiology
Table 6.2 Mesenteric cytokine production in Crohn’s disease
Study Year Journal Cytokine Expression Reference
Sideri etal. 2015 Cell Mol Gastroenterol
Hepatol
Tacr-1/-2, IL-17A Increased [107]
Leal etal. 2013 Int J Clin Exp Med LC3-II Reduced [108]
TLR-4 No difference
F4/80 No difference
IL-1β No difference
IL-6 No difference
Kredel etal. 2013 Gut IL-10, IL-6, TNF-alpha Increased [66]
Jung etal. 2013 Cytokine IL-6, IL-4, IL-13 Increased [109]
Peyrin-Biroulet etal. 2012 Gut CRP Increased [69]
Rodrigues etal. 2012 Clin Exp Immunol CRP Increased [80]
adiponectin Decreased
Leptin No difference
Sibartie etal. 2010 Inamm Bowel Dis TNF-alpha Increased [110]
IL-8 Increased
Karagiannides etal. 2006 Proc Natl Acad Sci USA NK-1R, IL-8 Increased [111]
Schäfer etal. 2006 J Gastroenterol Hepatol RANTES Increased [71]
IL-10 Increased
Paul etal. 2006 Inamm Bowel Dis Adiponectin Increased [112]
Macrophage colony-stimulating factor Increased
Leptin Increased
migration inhibitory factor Increased
Resistin No difference
Interleukin-6 No difference
Monocyte chemotactic protein-1 No difference
Schäfer etal. 2006 J Gastroenterol Hepatol VEGF No difference [113]
Yamamoto etal. 2005 Gut Adiponectin Increased [73]
IL-6 No difference
Barbier etal. 2003 Gut Leptin Increased [58]
Desreumaux etal. 1999 Gastroenterology TNF-alpha Increased [60]
Visceral adiposity
Ascendin
g
colon
Right
mesocolon
Small intestinal
mesentery
Ileum
Figure 6.2 Intraoperative image demonstrating the scale of the contribution made by the small intestine and right
mesocolon to visceral adiposity. The small intestinal mesentery and right mesocolon are continuous, thus supporting the
inclusion of the mesocolon in the umbrella term of “visceral adiposity.” There is a substantial mesenteric tissue mass at the
ileocecal junction. Lymph nodes are apparent throughout.
Mesentery as a regulatory hub 73
Over the past decade, increasing data have accumulated
demonstrating a key role for mesenteric-based immune
cell types. Wei et al. [98] showed that mesenteric B cells
inhibit the development of CD4
+
T cell–induced colitis.
ey achieve this by fi st homing to mesenteric nodes
and then altering recruitment of CD4
+
, CD8α
+
T cells to
adjacent intestinal mucosa [98] (Figure 6.4). Wei et al.
suggested that mesenteric lymph node–based B cells are
protective and indeed essential in regulating homeosta-
sis in adjacent intestinal mucosa. eir fi dings indicate
that mucosal events are directed from mesenteric lymph
node–derived immunologic and cellular activities and
involve coordinated interactions between B cells, T cells,
and NKcells [98].
Hammerschmidt et al. further explored this phenom-
enon [99]. ey demonstrated that stromal cells in mes-
enteric lymph nodes were crucial for imprinting surface
α4β7-integrin and CCR9 on T cells. Following imprinta-
tion, T cells then homed to adjacent intestine, a phenom-
enon referred to as “gut tropism.” Hammerschmidt et al.
suggest that gut homing T cells can only be generated in a
permissive lymph node environment [99].
In a landmark study, Diehl et al. demonstrated that
luminal microbiota can regulate the tracking of com-
mensal organisms to mesenteric lymph nodes [100]. Under
certain conditions (including antibiotic-induced dysbiosis
and Myd88 deciency) commensal tracking is altered.
eirndings point to an important role for the microbial
ecology in regulating the delivery of enteric antigens to
mesenteric lymph nodes [100].
Using an adoptive model of murine inammatory
bowel disease, Karlis et al. identifi d adoptively trans-
ferred dendritic cells in mesenteric lymph nodes [101].
eir homing to mesenteric nodes preceded the devel-
opment of mucosal abnormalities. Others have shown
that radiologic signs of visceral adiposity occur in early
Bacteria
Intestinal
submucosa/mucosa
Translocation
Mesenteric
lymph node
Bacterium
Colitis
T
cell
CD4
+
T cell
CD4
+
, CD8
+
T cell
Inhibit
B
cell
T
cell
Stromal
cell
Recruited
Body
B cell
CCR9 expression
CCR9
Homing
˜4°7
˜4°7 expression
–
–
+
+
–
Figure 6.4 Schematic illustration of the cellular and molecular interactions that occur in mesenteric lymph nodes and
effects on adjacent mucosal inammation and immunity.
Migration
Migration of neural crest cells
Dorsal mesentery
Migration
Neuroendocrine
cell
Developing
central nervous
system
neural crest
Figure 6.3 Schematic illustration of migration of neural
crest cells across the mesentery to reach the proximal
intestine. From there, they then migrate distally to popu-
late the entire intestine.
74 Mesenteric physiology
Crohn’s disease, prior to the development of mucosal dis-
ease [22,101–106].
When collated, these ndings demonstrate (Table 6.2) a
key role for mesenteric lymph nodes in coordinating muco-
sal inammatory and immunologic events in a manner
regulated by local microbial ecology. As many of these stud-
ies have been conducted in murine models, similar studies
should be undertaken in the human context.
MESENTERIC MESOTHELIAL PLASTICITY
Increasing evidence points to plasticity in mesenteric meso-
thelium, which has been partially dealt with in Chapter 4
(Table 6.3) [114–119]. Balogh etal. demonstrated that under
inammatory conditions, mesothelial cells separate from
the underlying basal lamina and transform to spindle-
shaped cells with increased release of pro- inammatory
cytokines including TGF-β [120]. Several studies examin-
ing submesothelial connective tissue, identifi d cells with
immunohistochemical features overlapping mesothelial
and mesenchymal cell types. Others suggest that mesenteric
mesothelium contains a subpopulation of cells with pluri-
potential properties [121,122].
We recently noted that when mesenteric mesothelia
are expanded ex vivo, they transform into spindle-shaped
cells in a TGF-β-dependent manner. ese are mesothe-
lium-derived mesenchymal cells and include a mixture of
activated broblasts, brocytes, and myobroblasts. We
examined their properties in Crohn’s disease and found
these correlated with disease activity, as well as circulating
brocyte levels (Figure 6.5) [37,123–126].
Taken together, these ndings indicate that mesenteric
mesothelium is not inert and does not simply function as
a barrier across which peritoneal dialysate is absorbed or
created [127]. Instead, it has a regenerative capacity that,
when one considers the mesentery is one of the largest
organs in the body, could be substantial (Figure 6.6) [37].
MESENTERIC MESOTHELIAL PLASTICITY
AND INTRA-ABDOMINAL PATHOLOGY
Although this topic will be expanded on in detail in the
following chapter, it merits reference in this chapter.
e concept that mesenteric mesothelium can transform
into mesenchyme could have major implications in several
pathologic contexts. In abdominal wall hernia, a mesothelial
sac develops that can reach sizeable proportions depending
on the size of the hernia. In inguinal herniae, a mesothelial
extension (the processus vaginalis) extends into the ingui-
nal canal and permits extrusion of abdominal contents into
the canal [128].
Postoperatively, peritoneal mesothelium regenerates
and lls in mesothelial defects within 48–72 hours
[129–133]. Neo-mesothelialization is also associated with
development of mesenchyme and a combination of both
occurs in adhesions. Adhesions differ considerably in mor-
phology and cellular composition but invariably involve
a combination of mesothelial and mesenchymal events in
varying proportions. Patients who have undergone abdomi-
nal surgery are at increased risk of developing adhesions
and requiring emergency surgery for intestinal obstruc-
tion. Despite several decades of extensive investigation of
Table 6.3 Studies investigating mesothelial plasticity
Study Year Journal Subject Pathology
Stimulation
with
TGF-β1
Inhibition of
MMT with
anti-
TGF-β1?
Phenotpyic
change
observed? Reference
Nasreen
etal.
2009 Am J
Physiol
Lung Cell
Physiol
Human Idiopathic
pulmonary
brosis
Yes No Ye s [117]
Strippoli
etal.
2008 Dis Models
Mech
Human Peritoneal
brosis
Yes No Ye s [119]
Li etal. 2013 PNAS Murine Hepatic brosis Ye s Ye s Ye s [115]
Sandoval
etal.
2013 J Pathol Human +
murine
Peritoneal
carcinomatosis
Yes Yes Yes [118]
Karki
etal.
2014 FASEB Human +
murine
Idiopathic
pulmonary
brosis
Yes No Ye s [114]
Loureiro
etal.
2013 PLOS ONE Human +
murine
Peritoneal
brosis
Yes Tamoxifen Yes [116]
Sources: Burke, J.P. etal., Br J Surg, 97(7), 1126, 2010; Burke, J.P. etal., Br J Surg, 97(6), 892, 2010; Burke, J.P. etal., Br J Surg, 96(5), 541,
2009; Sahebally, S.M. etal., Br J Surg, 100(12), 1549, 2013; diZerega, G., Peritoneal Surgery, Springer, New York, 1999; Garriga, V.
etal., Radiographics, 29(7), 2017, 2009.
Note: MMT, mesothelial to mesenchymal transformation; TGF-β, transforming growth factor beta.
Mesothelial secretion and absorption of peritoneal uid 75
adhesion formation, eff ctive preventative measures are
lacking. is relates to the fact that we continue to have a
poor understanding of the coordinated mesothelial and
mesenchymal activities that occur during adhesion forma-
tion [127,134]. Marked similarities occur between mesen-
teric mesothelium, submesothelial connective tissue, Toldt’s
fascia, and adhesion formation. ese point to a cellular and
molecular overlap and will be discussed in greater detail in
the following chapter.
MESOTHELIAL SECRETION AND
ABSORPTION OF PERITONEAL FLUID
Mesenteric mesothelium produces and absorbs peritoneal
uid at varying rates. In the male, 5 mL peritoneal uid
is produced daily. In females, this volume varies with the
menstrual cycle and ranges from 5 mL in the luteal phase
to 18 mL during menstruation [127,135,136]. Accumulation
of peritoneal uid increases dramatically in an array of
Mesothelial cells, green =cytokeratin,
blue=Hoechst (DNA stain)
Fibrocytes, green=collagen I, red/pink=CD45
shown as pink due to presence of Hoechst,
CD45 located around the nuclear membrane
(a) (b)
Fibroblast; red, vimentin; green, collagen I; green
overshadows, Hoechst blue at nucleus
Myofibroblast, red=alpha smooth muscle actin,
blue=Hoechst (DNA)
(c) (d)
Figure 6.5 Panel demonstrating different mesenchymal cell types generated following the exvivo culture of mesenteric
mesothelium. (a) Mesothelial cells approximately 24 hours following culture setup. (b) Fibrocytes. (c) Fibroblasts.
(d)Myobroblasts. (Continued)