Recent Advances in Angiogenesis and ... - Bentham Science

Thymus and Angiogenesis Recent Advances in Angiogenesis and Antiangiogenesis, 2009 41
direct by vascular endothelium-derived factors or
indirect, in the form of factors carried through the
circulation [1].
Fig. (1). Architecture of the human postnatal thymus (H&E,
x4).
A rich network of epithelial cells is found throughout
the cortex and medulla (Fig. 2) and based on their
structure and functions there six different subtypes
were described. These cells express mainly basal
cytokeratin and were used to propose a histogenetic
classification of thymoma [7]. Therefore, the thymus
is unique not only in terms of its functions and
dramatic changes during physiological involution but
also in structure, because it is the only organ in the
human body that has an epithelial stroma.
Fig. (2). The network of epithelial cells (cytokeratin, high
molecular weight, x400).
Besides lymphocytes and epithelial cells, the medulla
consists of a mixture of macrophages, antigenpresenting
cells, mast cells, eosinophils (mainly in the
interlobular septa in children), scattered myoid and
neuroendocrine cells. The functions and behavior of
all these cells that form the thymus parenchyma were
largely investigated but for some of them, there are
still uncertain aspects in human.
The particular development and structure of the
thymus is the base for some specific diseases, as
developmental abnormalities with associated
immunodeficiency, myasthenia gravis and tumors. A
broad spectrum of tumors was described in the
thymus. Among them, thymoma is the only specific
neoplastic proliferation of the organ and consists of
proliferating epithelial cells of the stroma. Thymomas
are relatively rare tumors with the most elusive
histological classification presently and unpredictable
behavior. In all the normal and pathologic conditions
of the thymus, angiogenesis was significantly less
investigated than in other organs. Angiogenesis, the
formation of new blood vessels from preexisting,
seems to be directly involved in the development and
involution of the normal thymus, and in different
pathologic conditions. Moreover, the thymus can be
considered as a source for proangiogenic molecules.
Of particular interest, mainly in pathology, is the
perivascular space (PVS), defined as the tissue found
within the capsule but outside the thymic epithelial
network [8]. PVS is a virtual space containing only
blood vessels in the infant thymus. It becomes more
prominent with aging and does not contain developing
thymocytes [9]. High endothelial venules can be
frequently identified in lymphocyte-rich PVS in both
normal thymus and in patients with myasthenia gravis.
The recirculation of peripheral lymphocytes was
hypothesized through a MECA-79 and L-selectin
dependent mechanism [9].
The formation of the blood and efferent lymphatic
vessels of the thymus is largely unknown and few data
are available about vasculogenesis and angiogenesis in
the normal human thymus and its pathologic
conditions.
2. BLOOD VESSELS
Arteries of the thymus derive from the internal
mammary, superior and inferior thyroid arteries and to
a lesser degree the pericardiophrenic arteries [10].
Arterial branches enter the interlobular connective
tissue and then in the parenchyma, near the
corticomedullary junction. This is why on histological
sections, the vessels with the largest lumen of the
parenchyma are found at the corticomedullary junction
(Fig. 3). On occasion, in the interlobular area can be
found pillow arterioles that regulate the blood flow.
Blood vessels of the parenchyma are surrounded by a
sheath of connective tissue that gradually becomes
thinner in small vessels [11]. Capillaries are found in
both cortex and medulla. Capillaries of the cortex
descend into the medulla and give rise to postcapillary
venules and then interlobular veins. Finally, the
venous system drains into the left brachiocephalic,
internal thoracic and inferior thyroid veins [10].
Vascular endothelial growth factor (VEGF) secretion
by thymic epithelial cells is required for normal
vascular architecture of the thymus [12].