Lymphatic lacunae of the human eye conjunctiva embedded within a stroma containing CD34+ telocytes.

An accurate identification of telocytes (TCs) was limited because of the heterogeneity of cell types expressing the markers attributed to TCs. Some endothelial lineage cells also could fit within the pattern of TCs. Such endothelial cells could line conjunctival lacunae previously assessed by laser confocal microscopy. We have been suggested that an accurate distinction of TCs from endothelial cells in the human eye conjunctiva could be achieved by use of CD31, CD34 and D2-40 (podoplanin); and that the conjunctival lacunae are in fact lymphatic. We aimed as testing the hypothesis by an immunohistochemical study on human eye conjunctiva biopsy samples. Samples of human eye conjunctiva from 30 patients were evaluated immunohistochemically by use of the primary antibodies: CD34, D2-40 and CD31. D2-40 was equally expressed within epithelia and laminae propria. Basal epithelial cells were D2-40 positive. Within the stromal compartment, the lymphatic marker D2-40 labelled several lymphatic vessels. CD31 labelled both vascular and lymphatic endothelial cells within the lamina propria. When capillary lymphatics were tangentially cut, they gave the false appearance of telocytes. Blood endothelial cells expressed CD34, whereas lymphatic endothelial cells did not. Stromal CD34-expressing cells/telocytes were found building a consistent pan-stromal network which was equally CD31-negative and D2-40-negative. The conjunctival lymphatic lacunae seem to represent a peculiar anatomic feature of eye conjunctiva. They are embedded within a CD34-expressing stromal network of TCs. The negative expression of CD31 and D2-40 should be tested when discriminating CD34-expressing TCs.

Endocardial tip cells in the human embryo - facts and hypotheses.

Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43-56 days) were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin), CD31, CD34, α-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting α-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.

Telocytes in the interstitium of human exocrine pancreas: ultrastructural evidence.

OBJECTIVES: Pancreatic interstitial cells are located among acini, ducts, nerves, and blood vessels. They are essential for pancreas development, physiology, and for oncogenic microenvironment. We identified cells with characteristic ultrastructural features of telocytes in pancreatic interstitium. Telocytes were initially described as interstitial Cajal-like cells, but it gradually became clear that they were a distinct novel cell type not directly related to canonical interstitial Cajal cells. METHODS: Serial ultrathin sections of human pancreatic tissue were studied by transmission electron microscopy. Computer analysis software was used to obtain 2-dimensional compositions from serial micrographs and to perform morphometry. RESULTS: Pancreatic telocytes appear as small-body cells with prolongations called telopodes. The ultrastructural features of telopodes are the following: (a) number: 1 to 3; (b) length: tens of micrometers; (c) moniliform aspect: with podoms (thicker portions) and podomers (thin segments, with a mean width of 60 nm, undetectable by light microscopy); (d) dichotomous branching forming a network; (e) establish homocellular and heterocellular junctions; (f) release of microvesicles/multivesicular bodies. Telopodes pass close to blood vessels, nerves, and pancreatic acinar cells and ducts. CONCLUSIONS: Telocytes are present as distinct interstitial cells in the exocrine pancreatic stroma. They act as important players in intercellular signaling via stromal synapses and shed vesicle transfer.

Telocytes in parotid glands.

The parotid histological structure includes acinar, ductal, and myoepithelial cells, surrounded by a connective stromal component. The parotid stroma is mostly regarded as an inert shell, consisting of septa, which divide the parenchyma. Telocytes were recently identified as a new stromal cell type in various organs, including exocrine pancreas. We aimed to evaluate telocytes presence in parotid stroma and whether their topographical features might support an involvement in parotid function modulation. Serial ultrathin sections of human and rat parotid glands were studied and compared by transmission electron microscopy. Two-dimensional concatenation of sequenced micrographs allowed the ultrastructural identification of parotid telocytes, with their specific long, thin, and moniliform prolongations (telopodes). Telocyte location appeared frequently as a strategic one, in close contact or vicinity of both secretory (acini and ducts) and regulatory (nerves and blood vessels) apparatuses. They were also found in the interacinar and the subductal stroma. Two previously reported telocyte markers (c-kit/CD117 and vimentin) were assayed by immunohistochemistry. Actin expression was also evaluated. Telocytes are making a network, especially by branching of their long telopodes. Elements of this telocyte network are interacting with each other (homocellular connections) as well as with other cell types (heterocellular connections). These interactions are achieved either by direct contact (stromal synapse), or mediated via shed microvesicles/exosomes. Since telocyte connections include both neurovascular and exocrine elements (e.g., acini and ducts), it is attractive to think that telocytes might mediate and integrate neural and/or vascular input with parotid function.

Neuroregeneration in neurodegenerative disorders.

BACKGROUND: Neuroregeneration is a relatively recent concept that includes neurogenesis, neuroplasticity, and neurorestoration--implantation of viable cells as a therapeutical approach. DISCUSSION: Neurogenesis and neuroplasticity are impaired in brains of patients suffering from Alzheimer's Disease or Parkinson's Disease and correlate with low endogenous protection, as a result of a diminished growth factors expression. However, we hypothesize that the brain possesses, at least in early and medium stages of disease, a "neuroregenerative reserve", that could be exploited by growth factors or stem cells-neurorestoration therapies. SUMMARY: In this paper we review the current data regarding all three aspects of neuroregeneration in Alzheimer's Disease and Parkinson's Disease.

Telocytes in human term placenta: morphology and phenotype.

In the last few years, a new cell type - interstitial Cajal-like cell (ICLC) - has been described in digestive and extra-digestive organs. The name has recently been changed to telocytes (TC) and their typical thin, long processes have been named telopodes (TP). To support the hypothesis that TC may also be present in human placenta and add to the information already available, we provide evidence on the ultrastructure, immunophenotype, distribution, and interactions with the surrounding stromal cells of TC in the villous core of human term placenta. We used phase-contrast microscopy, light microscopy of semithin sections, transmission electron microscopy, immunohistochemistry, and immunofluorescence of tissue sections or cell cultures, following a pre-established diagnostic algorithm. Transmission electron microscopy showed cells resembling TC, most (∼76%) having 2-3 very thin, longprocesses (tens to hundreds of micrometers), with an uneven calibre(≤0.5 µm thick) and typical branching pattern. The dilations of processes accommodate caveolae, endoplasmic reticulum cisternae, and mitochondria. These TC have close contacts with perivascular SMC in stem villi. In situ, similar cells are positive for c-kit, CD34, vimentin, caveolin-1, vascular endothelial growth factor (VEGF), and inducible nitric oxide synathase (iNOS). The c-kit-positive cells inconsistently co-express CD34, CD44, αSMA, S100, neuron-specific enolase, and nestin. Among cells with a morphologic TC profile in cell cultures, about 13% co-express c-kit, vimentin, and caveolin-1; 70% of the c-kit-positive cells co-express CD34 and 12% co-express iNOS or VEGF. In conclusion, this study confirms the presence of TC in human term placenta and provides their ultrastructural and immunophenotypic characterization.