The Potential of Berberine to Target Telocytes in Rabbit Heart.

A brand-new class of interstitial cells, called telocytes, has been detected in the heart. Telocytes can connect and transmit signals to almost all cardiomyocytes; this is highly interrelated with the occurrence and development of heart diseases. Modern studies have shown that berberine has a therapeutic effect on cardiovascular health. However, berberine's mechanism of action on the cardiovascular system through cardiac telocytes is unclear. Interestingly, 5 µm of berberine remarkably decreased the concentration of intracellular calcium and membrane depolarization in cultured telocytes, upregulated the expression of CX43 and ß-catenin, and downregulated the expressions of TRPV4 and TRPV1. Here, telocytes were identified in the vascular adventitia and intima, endocardium, myocardium, adventitia, and heart valves. Moreover, telocytes were broadly dispersed around cardiac vessels and interacted directly through gap junctions and indirectly through extracellular vesicles. Together, cardiac telocytes interact with berberine and then deliver drug information to the heart. Telocytes may be an essential cellular target for drug therapy of the cardiovascular system.

The Cellular Mechanism of Acupuncture for Ulcerative Colitis based on the Communication of Telocytes.

Acupuncture can ameliorate or treat diseases according to the meridian theory in traditional Chinese medicine (TCM); however, its mechanism has not been scientifically clarified. On the other hand, telocytes (TCs) are morphologically in accordance with the meridian system, which needs further cytological investigations and acupuncture confirmation. The present study showed that acupuncture could activate TCs in several ways, alleviating rabbit ulcerative colitis. TCs could cytologically communicate the acupoints, the acupuncture sites in skin with their corresponding large intestine by TC homo-cellular junctions, exosomes around TCs, and TC-mediated nerves or blood vessels. TCs expressed transient receptor potential vanilloid type 4, the mechanosensitive channel protein that can transduce the mechanical stimulation of acupuncture into biochemical signals transferring along the extremely thin and long TCs. Collectively, a cellular mechanism diagram of acupuncture was concluded based on TC characteristics. Those results also confirmed the viewpoint that TCs were the key cells of meridian essence in TCM.

Cellular Evidence for Telocytes Mediating Electroacupuncture to Ameliorate Obesity in Mice.

Electroacupuncture has been generally applied to target obesity, the principle of which is based on the meridian in traditional Chinese medicine. Although Telocytes (TCs) have been reported as the potential essence of meridians, their specific role in the electroacupuncture treatment of obesity remains unclear. Thus, we investigated the cellular evidence for TC-mediated electroacupuncture to alleviate obesity. Mice were divided into three groups as follows: electroacupuncture group (EA), control group (CG), and normal group (NG). The present study showed that the weight of perirenal white adipose tissue (rWAT), the serum level of total cholesterol, and the low-density lipoprotein cholesterol were all significantly decreased after electroacupuncture. Ultrastructurally, the prolongations (telopodes, Tps) of TCs were in direct contact with adipocytes, and lipid droplets were distributed on the surface of Tps. The proportions of double-positive fluorescent areas of TCs (CD34 and PDGFRα) were significantly elevated with concomitant elongated Tps in EA mice, as compared to those in CG mice. The expression of Cx43 and CD63 (gap junction and exosome markers) was significantly enhanced. These characteristics facilitated the transmission of electroacupuncture stimulation from skin to rWAT. We conclude that electroacupuncture relieved obesity by activating TCs morphologically, upregulating the gap junctions between TCs, and increasing the exosomes around TCs.

Tissue Micro-channels Formed by Collagen Fibers and their Internal Components: Cellular Evidence of Proposed Meridian Conduits in Vertebrate Skin.

In order to clarify fine structures of the hypothetical meridian conduits of Chinese traditional medicine (CTM) in the skin, the present study used light and transmission electron microscopy to examine fasciae in different vertebrate species. Collagen fiber bundles and layers were arranged in a crisscross pattern, which developed into a special tissue micro-channel (TMC) network, in a manner that was analogs to the proposed skin meridian conduits. It was further revealed that tissue fluid in lateral TMC branches drained into wide longitudinal channels, which were distinctly different from lymphatic capillary. Mast cells, macrophages, and extracellular vesicles such as ectosomes and exosomes were distributed around telocytes (TCs) and their long processes (Telopodes, Tps) within the TMC. Cell junctions between TCs developed, which could enable the communication between contiguous but distant Tps. On the other hand, winding free Tps without cell junctions were also uncovered inside the TMC. Tissue fluid, cell junctions of TCs, mast cells, macrophages, and extracellular vesicles within the TMC corresponded to the circulating "" ("Qi-Xue", i.e., information, message, and energy) of meridian conduits at the cytological level. These results could provide morphological evidence for the hypothesis that "meridians are the conduit for Qi-Xue circulation" in CTM.

Telocytes in Different Organs of Vertebrates: Potential Essence Cells of the Meridian in Chinese Traditional Medicine.

Telocytes (TCs) are very long, non-neuronal, somatic cells whose function is widely believed to be involved in providing connections between different cells within the body. The cellular characteristics of TCs in various organs have been studied by immunohistochemistry, double immunofluorescence and electron microscopy in different vertebrate species, and here we investigate the proposed properties of these cells in the context of the "meridian" in Chinese Traditional Medicine (CTM). The results show that TCs and their long extensions, telopodes (Tps) develop a complicated network by homo- and heterocellular junctions in the connective tissue throughout the body, which can connect the skin with distant organs. In concept, this is the analogue of ancient meridian maps connecting skin acupoints with the viscera. Various active cells and extracellular vesicles including exosomes move along Tps, which, along with developed mitochondria within the podoms of Tps, may account for the structural evidence for "Qi" (vital energy and signal communication) in CTM. Morphological associations of TCs with the nerve, vascular, endocrine, and immune systems are also compatible with previously proposed meridian theories in CTM. Close relationships exist between TCs and collagen fiber bundles and some structures in skin fascia provide the microanatomical support for acupuncture treatment based on the meridian principle. The dynamicity in the distribution and structure of TCs reflects the plasticity of the meridian at the cellular level. As the same attribute, both the meridian and the TC have been associated with various diseases. Here, we summarize structural analogues between the TC and the meridian, suggesting that TCs have the cytological characteristics of the CTM meridian. We, therefore, hypothesize that TCs are the "essence cells" of the CTM meridian, which can connect and integrate different cells and structures in the connective tissue.

Histological and immunohistochemical study of cardiac telocytes in a rat model of isoproterenol-induced myocardial infarction with a reference to the effect of grape seed extract.

INTRODUCTION: Cardiac telocytes (TCs) represent a unique type of cells that make a supportive network for stem cells that contribute in cardiac renewal, but their role during myocardial infarction (MI) is not clear. Grape seed extract (GSE) is a powerful natural antioxidant. AIM OF THE WORK: Quantitative study of cardiac TCs in a rat model of Isoproterenol (ISO)-induced MI, and to evaluate the effect of GSE on TCs and MI progression. MATERIALS AND METHODS: Seventy adult male albino rats were assigned into 4 groups; group I; control rats, group II received GSE (100mg/kg/day) dissolved in distilled water orally, group III received 2 intra-peritoneal injections of 85mg/kg ISO dissolved in saline on 14th and 15th day to induce MI, and group IV received GSE and ISO. Myocardium was obtained 1 and 14days after ISO i.e. on day 16 and day 30 respectively. Tissue was prepared for histological and immunohistochemical study of CD117 and CD34 as two markers for TCs. CD34 was used also as a marker for angiogenesis. RESULTS: Group III showed focal areas of myocardial infarction 1day and 14days after ISO. Degenerated cardiomyocytes showed loss of striation and hypereosinophilic vacuolated cytoplasm with condensed nuclei. Mononuclear cell infiltration and a significantly increased percentage area of fibrosis 14days after ISO were observed. CD117 and CD34 positive TCs were hardly detected 1day after ISO. Their number slightly increased 14days after ISO with insignificant difference to control. There was also a significant increase in the number of CD34 positive blood vessels 14days after ISO. Group IV showed much better histological picture with a significant decrease in the percentage area of fibrosis and a significant increase in the number of CD117 and CD34 positive TCs and the number of CD34 positive blood vessels as compared to group III. CONCLUSION: Telocytes were significantly decreased in MI. GSE reduced ISO-induced histological changes and increased the number of TCs that improved angiogenesis.

High-Dose Radiation-Induced Changes in Murine Small Intestinal Motility: Are the Changes in the Interstitial Cells of Cajal or in the Enteric Nervous System?

Murine small intestinal motility consists of phasic contraction from interstitial cells of Cajal (ICC) and migrating motor complexes (MMCs) from the enteric nervous system. The number of ICC is reduced in various gastrointestinal disorders, and this effect can be reversed once the disorder is resolved through cellular and tissue remodelling. Exposure to high-dose radiation can induce inflammation and alter intestinal motility. In this study, we investigated the changes in the small intestinal motility of 8- to 10-week-old male C3H/HeN mice after high-dose (13 Gy) irradiation. The aim of this study was to determine whether those changes are caused by changes in the ICC or enteric nervous system. After irradiation, the small intestine was dissected and stored in oxygenated Krebs-Ringer bicarbonate solution. The tension of contractions and intracellular membrane potentials were recorded at day 0, 1, 3 and 5 after irradiation and compared with those of sham-irradiated mice. Histological evaluation was performed by immunohistochemistry and apoptosis was evaluated. Quantitative real-time polymerase chain reaction (qPCR) for c-kit mRNA was also performed. Phasic contractions were not changed at day 0, 1, 3 and 5 after irradiation and did not significantly differ from those in the control mice. Slow waves were also sustained after irradiation. However, the frequency of migrating motor complexes (MMCs) was significantly higher at day 0 and 1 after exposure and the amplitude and area under the curve were significantly lower at day 3 after exposure compared with control mice. MMCs were recovered at day 5 with no difference from those of the control mice. ICC were detected after irradiation by immunohistochemistry for c-kit, and c-kit mRNA levels did not differ between sham-irradiated and irradiated mice. Histological evaluation showed that the most severe inflammation was detected at day 3 after irradiation, and apoptosis was detected only in the mucosa. Acetylcholine increased the contractility after irradiation, and tetrodotoxin decreased the number of MMCs in sham-irradiated and irradiated mice. N(w)-oxide-l-arginine (L-NA) increased the number of MMCs. MMCs were recovered after L-NA treatment at day 3 after irradiation. Sodium nitroprusside decreased the MMCs in sham-irradiated and irradiated mice. Exposure to high-dose radiation did not alter phasic contractions and slow waves in the small intestine of mice, which suggests that ICC and their functions may be sustained after high-dose irradiation. Mucosal inflammation was severe after irradiation and there were some changes in MMCs related to the enteric nervous system.

Near-infrared low-level laser stimulation of telocytes from human myometrium.

Telocytes (TCs) are a brand-new cell type frequently observed in the interstitial space of many organs (see www.telocytes.com ). TCs are defined by very long (tens of micrometers) and slender prolongations named telopodes. At their level, dilations-called podoms (~300 nm), alternate with podomers (80-100 nm). TCs were identified in a myometrial interstitial cell culture based on morphological criteria and by CD34 and PDGF receptor alpha (PDGFRα) immunopositivity. However, the mechanism(s) of telopodes formation and/or elongation and ramification is not known. We report here the low-level laser stimulation (LLLS) using a 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (with an output power of 60 mW) of the telopodal lateral extension (TLE) growth in cell culture. LLLS of TCs determines a higher growth rate of TLE in pregnant myometrium primary cultures (10.3 ± 1.0 µm/min) compared to nonpregnant ones (6.6 ± 0.9 µm/min). Acute exposure (30 min) of TCs from pregnant myometrium to 1 µM mibefradil, a selective inhibitor of T-type calcium channels, determines a significant reduction in the LLLS TLE growth rate (5.7 ± 0.8 µm/min) compared to LLLS per se in same type of samples. Meanwhile, chronic exposure (24 h) completely abolishes the LLLS TLE growth in both nonpregnant and pregnant myometria. The initial direction of TLE growth was modified by LLLS, the angle of deviation being more accentuated in TCs from human pregnant myometrium than in TCs from nonpregnant myometrium. In conclusion, TCs from pregnant myometrium are more susceptible of reacting to LLLS than those from nonpregnant myometrium. Therefore, some implications are emerging for low-level laser therapy (LLLT) in uterine regenerative medicine.