Telocytes in meninges and choroid plexus
Highlights
► Telocytes are a recently identified type of interstitial cells. ► We identified telocytes in rat meninges and choroid plexus. ► Telocytes form an interstitial network in the interstitium. ► Telocytes have direct cell–cell contacts with stem cells.
Introduction
Adult neurogenesis represents the generation of new neurons after the postnatal brain development has ended [1] and it is now a widely accepted phenomenon. A large body of evidence established that neural stem/progenitor cells (NPCs) are abundant in the sub-ventricular zone of the lateral ventricles (SVZ) and in the subgranular zone of the dentate gyrus. NPCs are able to differentiate to neurons and to migrate to the olfactory bulb and hippocampus, respectively [13]. However, recent data suggested that NPCs are also located in other regions of the brain, such as meninges [14], neocortex [17], amygdala [18] and brain stem [4]. Presumably they are triggered to differentiate by pathological conditions or injury. Stem cells are present in choroid plexus as well [16] and they have the potential to differentiate to different lineages, including neurons [9]. The function and capability of brain-spread NPCs to improve neurological deficits has still to be elucidated. Neurogenesis remains one of the main therapy targets to be explored in stroke and neurodegenerative diseases [5].
Telocytes (TCs) are a novel type of interstitial cells characterized by a small cell body and extremely long, moniliform, cell processes – telopodes (Tps) [6], [20], [21]. TCs have a specific phenotype, including the microRNA expression [3]. TCs establish contacts with blood capillaries, nerve fibers and stem cells. TCs and stem cells function as a tandem [21]. TCs surround morphologically stem cells and synthesize and release growth factors, such as VEGF or NO [11]. Therefore, TCs presumably have an important role for tissue adaptation to injury and stem cell activation. TCs are present in a wide variety of organs in various species, including mammals and reptiles [6], [20]. We have previously shown, by electron microscopy, the presence of TCs in heart [19], lungs [22] and skeletal muscle [23] in tandem with resident or migrated stem cells. TCs release shed vesicles and exosomes, sending macromolecular signals to neighbor cells (including stem cells), possibly regulating their transcriptional activity and activation [23].
The main objective of this study was to explore whether TCs are present in meninges and choroid plexus/ependymal layer, structures involved in important regulatory processes of the brain function.
Section snippets
Tissue samples
Rat meninges and choroid plexus samples were obtained from three fetal and three 6-months old Wistar rats and three 6-months old C57 black mice, sacrificed for other experimental purposes. This study was approved by the Bioethics Committee of the “Victor Babeş” National Institute of Pathology, Bucharest, according to generally accepted international standards.
Transmission electron microscopy (TEM)
TEM was performed on small (1 mm3) tissue fragments, processed according to routine Epon-embedding procedure, as we previously described
Results
TEM showed that interstitial cells with long processes do exist in fetal and adult rat meninges (Fig. 1A and B) and choroid plexus (Fig. 1, Fig. 2). These cells fulfill ultrastructural criteria for TCs (Fig. 1, Fig. 2): long (tens of micrometers) and thin (50–200 nm) cellular processes – Tps. In fetal meninges (Fig. 1A) TCs were more numerous compared with adult meninges (Fig. 1B). In adult meninges TCs were present mainly around large blood vessels and extended long Tps among arachnoid
Discussion
Both meninges and choroid plexus are structures that modulate brain function during embryogenesis and adult life. Interestingly, both meninges [25] and choroid plexus [26] include, beside a wide variety of components, interstitial cells, with incompletely elucidated functions to date. By TEM and immunofluorescence, we showed here that newly described interstitial cells TCs, with their peculiar Tps (extremely thin and long processes; almost unnoticeable due to their thickness) are located in
Conclusions
We present here evidence for the presence of TCs in meninges and choroid plexus, two structures which contain putative stem cells and might play a role in neuroregeneration. In these regions TCs and stem cells are in close contact, suggesting regulation through intercellular signaling. Thus, TCs might have an important role in assisting the differentiation and migration of stem cells during different neurogenesis stages.
Conflicts of interest statement
The authors declare no conflict of interest.
Acknowledgments
This study was partially supported by the Sectorial Operational Programme, Human Resources Development, financed from the European Social Fund and by the Romanian Government under the contract number POSDRU/89/1.5/S/64109. Prof. L.M. Popescu thanks Cord Blood Center (Cluj) for financial assistance.
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These authors contributed equally to the work.