Pericytes are the perivascular or mural cells of micro vessels. They are of mesenchymal origin and capable of differentiating into a number of different cell lineages. They are intimately associated with endothelial cells and communicate with them via direct physical contact or through paracrine signaling pathways. These interactions are important for blood vessel maturation, remodelling, and maintenance. Pericytes are versatile and their varying morphological characteristics and distribution make them difficult to study. The lack of universal pericytes markers is a major problem. A number of different functions have been attributed to pericytes, and in some organs they have more specific roles. The role of pericytes in tumor vessels is debated, but pericytes may contribute to stability, and might protect the vessels from antiangiogenic therapy. Understanding the process of angiogenesis in angiogenesis dependent diseases role of pericytes may be of therapeutic benefit.This article gives an overview of pericytes their role in health and disease particularly in relation to oral cavity.

1. International Journal of Oral & Maxillofacial Pathology. 2014;5(1):02-07 ISSN 2231 – 2250
Available online at http://www.journalgateway.com or www.ijomp.org
©2014 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved
Pericytes in Health and Disease
Prashant B Munde, Shubhangi P Khandekar, Alka M Dive, Neha R Upadhyaya
Abstract
Pericytes are the perivascular or mural cells of micro vessels. They are of mesenchymal origin
and capable of differentiating into a number of different cell lineages. They are intimately
associated with endothelial cells and communicate with them via direct physical contact or
through paracrine signaling pathways. These interactions are important for blood vessel
maturation, remodelling, and maintenance. Pericytes are versatile and their varying morphological
characteristics and distribution make them difficult to study. The lack of universal pericytes
markers is a major problem. A number of different functions have been attributed to pericytes, and
in some organs they have more specific roles. The role of pericytes in tumor vessels is debated,
but pericytes may contribute to stability, and might protect the vessels from antiangiogenic
therapy. Understanding the process of angiogenesis in angiogenesis dependent diseases role of
pericytes may be of therapeutic benefit.This article gives an overview of pericytes their role in
health and disease particularly in relation to oral cavity.
Key-words: Disease; Endothelial Cell; Functions; Markers; Origin; Pericytes; Structure.
Prashant B Munde, Shubhangi P Khandekar, Alka M Dive, Neha R Upadhyaya. Pericytes in Health and
Disease. International Journal of Oral & Maxillofacial Pathology; 2014:5(1):02-07. ©International Journal of
Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All
Rights Reserved.
Introduction
Pericytes also known as mural cells or
perivascular cells are contractile cells
located on the abluminal side of the
endothelium in micro vessels. They
communicate with endothelial cells via direct
physical contact or through paracrine
signaling pathways. These interactions are
important for blood vessel maturation,
remodelling, and maintenance.
1
Pericytes
are also known as Rouget cells after their
discoverer, Charles Rouget, but the more
suitable term pericyte (peri; around, cyte;
cell) was coined by Zimmerman in the early
1920s, as the cells were found to wrap
themselves around and along the
vessel.They share many characteristics with
smooth muscle cells that surround larger
blood vessels as well as fibroblasts and
myofibroblasts.
2
Pericytes are of mesenchymal origin and
have been shown to have mesenchymal
stem cell properties capable of differentiating
into other types of mesenchymal cells,
including fibroblasts, osteoblasts,
chondrocytes, and adipocytes.
3,4
Thus this
article covers the areas of origin, structure,
pericyte’s interaction with endothelial cell,
markers, functions; and role of pericytes in
health and disease. It provides the current
state of knowledge and thoughts for future
investigations in these areas.
Morphology
Morphological characteristics vary from one
tissue to another, within the same tissue, or
even within the same capillary bed.
Pericytes normally possess a cell body with
a prominent nucleus and a small content of
cytoplasm with several long processes
embracing the abluminal endothelial wall
(Figure 1). The cells are embedded within
the basement membrane which surrounds
capillary tubes, and in vitro studies have
shown that pericytes and endothelial cells
contribute to the formation of this basement
membrane. Pericytes are intimately
associated with the endothelial surface and
their cytoplasmic protrusions contact
endothelial cells along the length of the
vessel.
2
Pericyte density also varies between
different areas of the body, and morphology
differs depending on species, tissue, and
type of vessel and stage of vessel.
Pericytes – Endothelial cell interactions
Blood vessels constitute the elaborate
transport system by adequate supply of
oxygen and nutrients, and removal of waste
material from our body. Blood vessels are
composed of two or three different cell
types, depending on the type of vessel and
its size. All vessels have an inner lining of
endothelial cells surrounded by perivascular
mural cells (pericytes and vascular smooth
muscle cells, vSMC). The smallest-diameter
Review Article

2. ISSN 2231 – 2250 Pericytes in Health and... 3
vessels, i.e. arterioles, venules, and
capillaries, are associated with solitary
pericytes, while multiple concentric layers of
vSMC surround larger vessels. The largest
arteries have a third outer layer of adventitial
fibroblasts.
5
Figure 1: Pericytes are in close association
with the abluminal side of micro vessel
endothelial cells. Protruding cytoplasmic
processes wrap themselves around the
vessel wall. (Courtesy: Nisancioglu MH, et
al., 2010
5
)
The cell-cell contacts between pericytes and
endothelial cells are crucial for the regulation
of vascular formation, stabilization,
remodelling, and function and differ
depending on the activation state of the
blood vessel.
6
There are several different
types of cell surface contacts between
pericytes and endothelial cells.
7
In peg and
socket contacts cytoplasmic processes from
either cell type insert into invaginations of
the other cell. In adherens junctions
pericytes and endothelial cells connect their
cytoskeleton through cytoplasmic
membranes with catenins and cadherins. In
gap junction adjacent cell membranes fuse
or are separated by a 2-3 nm space.
8
(Figure
2) Interactions between endothelial cells and
mural cells (pericytes and vascular smooth
muscle cells) in the blood vessel wall have
recently come into focus as central
processes in the regulation of vascular
formation, stabilization, remodeling, and
function. Failure or abnormal interactions
between the two cell types, results in
cardiovascular defects, tumor angiogenesis,
diabetic microangiopathy, ectopic tissue
calcification, and stroke.
6
Pericytes in Health
In Dental pulp: Pericytes are capillary
associated fibroblasts. They are present
partially encircling the capillaries. They have
contractile properties and capable of
reducing the size of the capillary lumen.
Their nuclei can be distinguished as round
or oval bodies closely associated with the
outer surface of the terminal arterioles or
pre-capillaries (Figure 3) Pre-capillaries
exhibit a complete or incomplete single layer
of muscle cells surrounding the endothelial
lining.
9
Figure 2: Pericytes surrounding endothelial
cells share the basement membrane with
endothelial cells. A direct pericyte–
endothelial contact is established via
junctional complexes located to peg– socket
contacts at sites were the basement
membrane is absent. (Courtesy:
Nisancioglu MH, et al., 2010
5
)
Figure 3: Peripheral pulp and small arteriole
or pre-capillaries exhibiting two thin layers
of smooth muscle cells surrounding the
endothelial cell lining of vessel, Nucleus of
pericytes. (Courtesy: Kumar GS, 2011
9
)
In Periodontal ligament (PDL):
Periodontal ligament maintains homeostasis
in periodontal tissues by supplying stem
cells located around blood vessels.
Periodontal ligament stem cells possess
pericytes-like characteristics and may
localize as pericytes in the PDL. This is
useful in stem cell biology in periodontal
research and stem cell-based periodontal
therapy.
10
The relative frequency of
pericytes to endothelial cells varies also in
different tissues.
11
The pericytes coverage

3. 4 Prashant B Munde, et al. ISSN 2231 - 2250
of the endothelium is partial and can range
from 10-50% with the highest found in the
central nervous system (CNS).
12
In the
brain, pericytes contribute to the blood-brain
barrier (BBB) and maintain the integrity of
structural vessels.
13
Pericytes have special
functions in many organs and have
therefore been given additional names in
these organs i.e. Itoh cells or Hepatic
stellate cells (HSC) in the liver and
mesangial cells in the kidney.
14
Pericytes Functions
Regulation of blood flow: Vascular smooth
muscle cells of larger vessels regulate blood
flow via contraction and relaxation. It has
long been postulated that pericytes in a
similar fashion are contractile cells that
contribute to the regulation of blood flow via
communication with endothelial cells.
1
Inflammation: The complex process of
inflammation involves a response from both
the local tissue and the vasculature. The
vascular component is characterized by
increased vessel permeability to fluid,
macromolecules, and immune cells.
Pericytes contribute to the inflammatory
response in these events, mainly through
fine-tuning of the vasculature.
3
Immune function: Several studies show
that brain pericytes might serve as
macrophages. Pericytes were also reported
to express numerous marker components of
macrophages. Some argue that the reported
observations might relate to perivascular
macrophages instead of pericytes.
15
Wound healing: Mesenchymal cells present
in early wounds were divided into two
groups: primitive mesenchymal cells and
macrophages. Primitive mesenchymal cells
incorporated in the thick basement
membrane of recently formed capillaries,
and differentiate into fibroblasts. After
becoming encased in vascular basement
membrane these cells, pericytes featured
areas of cytoplasmic contact with underlying
endothelium. It is proposed that the pericyte-
endothelial “contacts” act as a regulatory
mechanism for capillary proliferation during
wound healing.
16
Vascular development / Angiogenesis:
Pericytes play an important role in the
formation of blood vessels. The formation of
stable and mature blood vessels is achieved
via the production of extra cellular matrix
(ECM) and recruitment of pericytes and
vascular smooth muscle cells (VSMC).
17
The
role of pericytes in tumours is unclear.
Potentially, pericytes may stabilise blood
vessels, inhibit endothelial proliferation,
maintain capillary diameter, regulate blood
flow, and provide endothelial survival signals
via heterotypic contacts and soluble factors.
There is a mutual interplay between
endothelial cells and pericytes in the
direction of the angiogenic process,
assigning to the pericytes a putative
morphogenetic role.
18
Tissue-specific functions
Pericytes acquire specialized characteristics
in different organs, depending on the
functions of each organ. Both pericyte
density and vessel coverage, for example,
vary among tissues. In certain organs, such
as the kidney, liver, and brain, pericytes
appear to have more specialized roles. Role
of pericytes may be of therapeutic benefit in
understanding the process of angiogenesis
in a number of angiogenesis dependent
diseases such as cancer, atherosclerosis,
scars, keloids, psoriasis, ulcers, wound
healing, arthritis, diabetes and retinopathy.
5
Markers for Pericytes
Pericytes are largely defined based on
morphology and location, but they are also
commonly identified using molecular
markers. Initial methods to identify better
markers for pericytes had limited success
which relied on immuno-histochemistry for a
combination of cytoskeletal proteins thought
to be uniquely expressed by pericytes.
Pericytes were found to stain for both
muscle and non-muscle isoactin.
15
None of
the markers routinely used in the
identification of pericytes, is completely
specific for pericytes and neither are they
expressed by pericytes in all tissues and
organs.
6
Thus, the lack of a single marker for
pericytes can give rise to misinterpretation of
results and defining the true role of pericytes
becomes difficult. Recently, regulator of G
protein signalling 5 was discovered to be a
novel Pericyte gene. (Table 1)
Pericytes in tumors
The rapidly growing tumours have a
tendency to develop an immature vascular
phenotype with continuous micro vessel
growth and remodelling. These
abnormalities result from defects in both
compartments of tumor vasculature,
endothelial cells and pericytes.
19
Tumor
pericytes are different from normal pericytes,
just like tumor vessels differ from those of

4. ISSN 2231 – 2250 Pericytes in Health and... 5
the normal vasculature.(Figure 4) The cells
are often loosely attached to the
endothelium and extend cytoplasmic
processes deep into the tumor tissue.
20
Pericyte density and vessel coverage is
generally reduced in tumors, but it seems to
vary and depends on tumor type.
21
Molecular
Marker
Expression
αSMA
Expressed only locally by
pericytes in tumor
vasculature contractile
filaments
PDGFR-β Tyrosine kinase receptor
Desmin
Reactive to developing
and developed pericyte
contractile filaments
3G5
Ganglioside
antigen
Specific for a pericyte
surface ganglioside
NG2
Neuron-
glial 2
Tyrosine kinase receptor
expressed in pericytes in
early stages of
angiogenesis
RGS5
Regulator
of G-protein
signaling-5
Novel marker for
pericytes and vascular
smooth muscle cells
GTPase activating
protein1
Table 1: Microscopic imaging markers for
pericytes (Courtesy: Armulik A, et al.,
6
2005)
Hemangiopericytoma: It is a tumor thought
to be derived from pericytes. It consists of
numerous vascular channels showing plump
endothelial nuclei and indistinct cytoplasm.
These cells at the periphery of the
capillaries are malignant pericytes and they
often exhibit cellular pleomorphism,
nuclear hyperchromatism and
increased abnormal mitotic activity, etc.
The malignant pericytes are often spindle
shaped and these cells are often
haphazardly arranged within the tumor. The
blood vessels often exhibit irregular
branching and therefore produce a typical
'stag-horn' appearance. The demonstration
of capillary basement membrane by silver-
reticulin stain reveals that these malignant
pericytes are present outside the basement
membrane and these cells are sharply
demarcated from endothelial cells by the
'peri-endothelial ring' of reticulin fibers.
22
Hemangioma: The clinical phases of
Hemangioma have physiological differences,
correlated with immunophenotypic profiles
by Takahashi et al. During the early
proliferative phase (0-12 months) the tumors
express proliferating cell nuclear antigen
(pericytesna), vascular endothelial growth
factor (VEGF), and type IV collagenase, the
former two localized to both endothelium
and pericytes, and the last to endothelium.
The vascular markers CD 31, von
Willebrand factor (vWF), and smooth muscle
actin (pericyte marker) are present during
the proliferating and involuting phases, but
are lost after the lesion is fully involuted.
23,24
Figure 4: Pericytes in healthy tissues are in close contact with the endothelium. In tumors,
pericyte numbers are reduced, and are loosely attached to the tumor micro vessels. (Courtesy:
Nisancioglu MH, et al., 2010
5
)
The Glomus Tumour: The glomus
neoplasms are benign, circumscribed found
in the superficial soft tissues, are
characterized by an organoid structure, and
are frequently but not always painful. It has
been shown by Murray and Stout' that the
so-called "epithelioid" cells of the glomus
tumour are pericytes, originally described by
the Swiss histologist Zimmermann.
Incidentally, Enterline and Roberts have
described a neoplasm composed of
pericytes derived from lymph vessels.

5. 6 Prashant B Munde, et al. ISSN 2231 - 2250
Pericytes of the hemangiopericytoma are not
frequently elongated and spindle shaped,
somewhat resembling a leiomyoblast. While
pericytes of the glomus tumour are rounded
or epithelioid, this resemblance has led to a
mistaken diagnosis of a vascular leiomyoma
or fibro sarcoma.
25
Congenital epulis: The congenital epulis
(gingival granular cell tumor) is a rare lesion
of unknown origin found only in newborn
infants. The various proposed cells of origin
are of the odontogenic epithelium,
undifferentiated mesenchymal cells,
pericytes, fibroblasts, smooth muscle cells,
nerve related cells, and histiocytes. Cells
which appeared to be in a transitional state,
not yet true granular cells were found
juxtaposed to the vessels in the position of
pericytes. Fine-structure details of these
cells were consistent with pericytes. Cells of
this type found farther from the vessels
appeared more like the typical granular cells.
The cells were filled with structures of the
autophagic type devoid of normal cell
organelles. These findings support the
theory that these are nonneoplastic,
degenerative, or reactive lesions arising
from a mesenchymal cell, possibly the
pericyte.
26
Conclusion
Pericytes are contractile cells that wrap
around the endothelial cells of capillaries
and venules throughout the body. Pericytes
are embedded in basement membrane
stabilize and monitor the maturation of
endothelial cells and communicate with
endothelial cells by direct physical contact
and paracrine signaling. This is important for
pericyte differentiation to other types of
mesenchymal cells. Damage to a tissue
initiates proliferation of fibroblasts, activation
of fibroblasts to myofibroblasts, and the
formation of new blood vessels. Endothelial
cells and pericytes are interdependent, so
failure of proper communication between the
two cells can lead to numerous human
pathologies. With time, a number of other
functions have been attributed to pericytes,
and it seems like we are now only starting to
understand the complexity of this versatile,
controversial and highly intriguing cell type.
Acknowledgement
We would like to acknowledge all the staff
members of department of Oral Pathology for
their support and guidance.
Author Affiliations
1.Dr.Prashant B. Munde, Postgraduate Student,
2.Dr.Shubhangi P. Khandekar, Professor,
3.Dr.Alka M. Dive, Professor and Head,
4.Dr.Neha R. Upadhyaya, Postgraduate Student,
Department of Oral and Maxillofacial Pathology,
Maharashtra University of Health Sciences,
Nashik, VSPM's Dental College and Research
Centre, Digdoh Hills, Hingna Road, Nagpur,
India.
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Corresponding Author
Dr. Prashant Munde,
Department of Oral Pathology,
VSPM's Dental College and Research
Centre, Digdoh hills,
Hingna Road, Nagpur, India.
Ph: +91 9552982232
E-mail: pinkclimate@gmail.com
Source of Support: Nil, Conflict of Interest: None Declared.