Evidence for progressive reduction and loss of telocytes in the dermal cellular network of systemic sclerosis

Telocytes, a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including human skin. Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease characterized by fibrosis of the skin and internal organs. We presently investigated telocyte distribution and features in the skin of SSc patients compared with normal skin. By an integrated immunohistochemical and transmission electron microscopy approach, we confirmed that telocytes were present in human dermis, where they were mainly recognizable by their typical ultrastructural features and were immunophenotypically characterized by CD34 expression. Our findings also showed that dermal telocytes were immunophenotypically negative for CD31/PECAM‐1 (endothelial cells), α‐SMA (myofibroblasts, pericytes, vascular smooth muscle cells), CD11c (dendritic cells, macrophages), CD90/Thy‐1 (fibroblasts) and c‐kit/CD117 (mast cells). In normal skin, telocytes were organized to form three‐dimensional networks distributed among collagen bundles and elastic fibres, and surrounded microvessels, nerves and skin adnexa (hair follicles, sebaceous and sweat glands). Telocytes displayed severe ultrastructural damages (swollen mitochondria, cytoplasmic vacuolization, lipofuscinic bodies) suggestive of ischaemia‐induced cell degeneration and were progressively lost from the clinically affected skin of SSc patients. Telocyte damage and loss evolved differently according to SSc subsets and stages, being more rapid and severe in diffuse SSc. Briefly, in human skin telocytes are a distinct stromal cell population. In SSc skin, the progressive loss of telocytes might (i) contribute to the altered three‐dimensional organization of the extracellular matrix, (ii) reduce the control of fibroblast, myofibroblast and mast cell activity, and (iii) impair skin regeneration and/or repair.     

Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation finally leading to extensive tissue fibrosis and resulting in a stiff colon unable to carry out peristalsis or to resorb fluids. Telocytes, a peculiar type of stromal cells, have been recently identified in the human gastrointestinal tract. Several roles have been proposed for telocytes, including mechanical support, intercellular signalling and modulation of intestinal motility. The aim of the present work was to investigate the presence and distribution of telocytes in colonic specimens from UC patients compared with controls. Archival paraffin‐embedded samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were identified by CD34 immunohistochemistry. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few telocytes were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. In the muscle layers and myenteric plexus of early fibrotic UC, telocytes were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of telocytes was reduced or even completely absent around smooth muscle bundles and myenteric plexus ganglia, paralleling the loss of the network of interstitial cells of Cajal. In UC, a loss of telocytes accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility.     

Telocytes play a key role in prostate tissue organisation during the gland morphogenesis

Telocytes are CD34‐positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34‐positive cells are found at the periphery of the developing alveoli, later in the same region, c‐kit‐positive cells and cells positive for both factors are verified and CD34‐positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF‐β1 and are ER‐Beta (ERβ) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development.     

Telocytes in minor salivary glands of primary Sjögren's syndrome: association with the extent of inflammation and ectopic lymphoid neogenesis

It has been recently reported that telocytes, a stromal (interstitial) cell subset involved in the control of local tissue homeostasis, are hampered in the target organs of inflammatory/autoimmune disorders. Since no data concerning telocytes in minor salivary glands (MSGs) are currently available, aim of the study was to evaluate telocyte distribution in MSGs with normal architecture, non‐specific chronic sialadenitis (NSCS) and primary Sjögren's syndrome (pSS)‐focal lymphocytic sialadenitis. Twelve patients with pSS and 16 sicca non‐pSS subjects were enrolled in the study. MSGs were evaluated by haematoxylin and eosin staining and immunofluorescence for CD3/CD20 and CD21 to assess focus score, Tarpley biopsy score, T/B cell segregation and germinal center (GC)‐like structures. Telocytes were identified by immunoperoxidase‐based immunohistochemistry for CD34 and CD34/platelet‐derived growth factor receptor α double immunofluorescence. Telocytes were numerous in the stromal compartment of normal MSGs, where their long cytoplasmic processes surrounded vessels and encircled both the excretory ducts and the secretory units. In NSCS, despite the presence of a certain degree of inflammation, telocytes were normally represented. Conversely, telocytes were markedly reduced in MSGs from pSS patients compared to normal and NSCS MSGs. Such a decrease was associated with both worsening of glandular inflammation and progression of ectopic lymphoid neogenesis, periductal telocytes being reduced in the presence of smaller inflammatory foci and completely absent in the presence of GC‐like structures. Our findings suggest that a loss of MSG telocytes might have important pathophysiological implications in pSS. The specific pro‐inflammatory cytokine milieu of pSS MSGs might be one of the causes of telocyte loss.     

Immunohistochemical biomarkers and distribution of telocytes in ApoE−/− mice

Telocytes had been identified as a peculiar stromal cell type implicated in tissue homeostasis and the development and pathophysiology of diseases. Telocyte existed in most organs and tissues in humans and animals. However, few studies have examined telocytes in ApoE gene deficient mice. In our studies, we verified the existence, the morphology and immunohistochemical characteristics of telocytes in critical organs of the ApoE^?/? mice. Male adult ApoE^?/? mice were selected as an experimental model. Immunohistochemical bio‐markers, such as CD34, CD117, CD28, Vimentin and PDGFR‐α were utilized to determine the distribution and morphology of telocytes in the heart, liver and kidney. Telocyte expressed positively for CD34 and CD117, and partial telocyte and telopode expressed positively for PDGFR‐α in heart and liver, but negatively in kidney. Double immunofluorescence assays for CD28/Vimentin, CD34/CD117 and CD34/PDGFR‐α were used to demonstrate the biochemistry speciality of telocytes, respectively. The evidence of telocytes in the ApoE^‐/‐ mice is the first step of our sturdy, which aims to demonstrate changes in telocytes in atherosclerosis in this animal model.     

Telocytes accompanying cardiomyocyte in primary culture: two- and three-dimensional culture environment

Recently, the presence of telocytes was demonstrated in human and mammalian tissues and organs (digestive and extra-digestive organs, genitourinary organs, heart, placenta, lungs, pleura, striated muscle). Noteworthy, telocytes seem to play a significant role in the normal function and regeneration of myocardium. By cultures of telocytes in two- and three-dimensional environment we aimed to study the typical morphological features as well as functionality of telocytes, which will provide important support to understand their in vivo roles. Neonatal rat cardiomyocytes were isolated and cultured as seeding cells in vitro in two-dimensional environment. Furthermore, engineered myocardium tissue was constructed from isolated cells in three-dimensional collagen/Matrigel scaffolds. The identification of telocytes was performed by using histological and immunohistochemical methods. The results showed that typical telocytes are distributed among cardiomyocytes, connecting them by long telopodes. Telocytes have a typical fusiform cell body with two or three long moniliform telopodes, as main characteristics. The vital methylene blue staining showed the existence of telocytes in primary culture. Immunohistochemistry demonstrated that some c-kit or CD34 immuno-positive cells in engineered heart tissue had the morphology of telocytes, with a typical fusiform cell body and long moniliform telopodes. Also, a significant number of vimentin+ telocytes were present within engineered heart tissue. We suggest that the model of three-dimensional engineered heart tissue could be useful for the ongoing research on the functional relationships of telocytes with cardiomyocytes. Because the heart has the necessary potential of changing the muscle and non-muscle cells during the lifetime, telocytes might play an active role in the heart regeneration process. Moreover, telocytes might be a useful tool for cardiac tissue engineering.     

Distribution and characteristics of telocytes as nurse cells in the architectural organization of engineered heart tissues

Interstitial Cajal-like cells are a distinct type of interstitial cell with a wide distribution in mammalian organs and tissues,and have been given the name"telocytes".Recent studies have demonstrated the potential roles of telocytes in heart development,renewal,and repair.However,further research on the functions of telocytes is limited by the complicated in vivo environment.This study was designed to construct engineered heart tissue(EHT)as a three-dimensional model in vitro to better understand the role of telocytes in the architectural organization of the myocardium.EHTs were constructed by seeding neonatal cardiomyocytes in collagen/Matrigel scaffolds followed by culture under persistent static stretch.Telocytes in EHTs were identified by histology,toluidine blue staining,immunofluorescence,and transmission electron microscopy.The results from histology and toluidine blue staining demonstrated widespread putative telocytes with compact toluidine blue-stained nuclei,which were located around cardiomyocytes.Prolongations from the cell bodies showed a characteristic dichotomous branching pattern and formed networks in EHTs.Immunofluorescence revealed positive staining of telocytes for CD34 and vimentin with typical moniliform prolongations.A series of electron microscopy images further showed that typical telocytes embraced the cardiomyocytes with their long prolongations and exhibited a marked appearance of nursing cardiomyocytes during the construction of EHTs.This finding highlights the great importance of telocytes in the architectural organization of EHTs.It also suggests that EHT is an appropriate physical and pathological model system in vitro to study the roles of telocytes during heart development and regeneration.     

Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34 + fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed.     

Presence,localization and morphology of TELOCYTES in developmental gonads of fishes

Telocytes are a new defined type of interstitial cells, considered as a stem cell, with very long and thin cytoplasmic extensions. They are present in the vertebrates, and may participate in tissue remodeling. In fish, during gonadal development, the events that culminate with the germinal epithelium formation are well known. However, the interstitial compartment remains poorly explored, although it may have a great contribution to the morpho-functional changes that occur in the gonad. As in other organisms, in fish, the interstitium consists especially of connective tissue elements. However, until now, there are no reports of the presence and the action of the telocytes in the connective tissue of gonads of fish. Thus, this study aimed to detect the presence, localization and morphology of telocytes during the gonadal development of several species of fish. The gonads were analyzed by light microscopy, transmission electron microscopy and immunohistochemistry for localization of CD34, Vimentin, and metalloproteinases. The presence of two proteins characteristics of mesenchymal cell was detected in cells of the gonads of all species. In addition, they presented a typical morphology of telocytes, showing cellular extensions. Gonadal telocytes also presented positive response to metalloproteinases. In mammals, telocytes can undergo de-differentiation contributing to the reorganization of the extracellular matrix. This role may be performed by the metalloproteinases detected here. The detection of Vimentin and CD34 in the same cellular type, associated with its morphological characteristics, allows us to conclude that some interstitial cells in Teleostei are considered telocytes, identical to the ones already described in mammals and other vertebrates.     

Telocytes in the Spleen

Telocytes, a novel type of interstitial cells with very long and thin prolongations, have been identified in many organs in mammals. At present, the ultrastructural, immunocytochemical and electrophysiological properties of telocytes in multiple organs have been understood. However, telocytes in spleen, especially their roles in spleen have not been reported. The aim of this study was to investigate the ultrastructure, distribution and immunophenotypes of splenic telocytes. Rat spleen was harvested for the ultrastructure analysis by transmission electron microscopy (TEM). The primary culture of telocytes was performed after combined enzymatic digestion. The characteristic morphology was analyzed by a scanning electron microscopy (SEM). It was shown that telocytes displayed a piriform/spindle/triangular shape with long and slender telopods and extremely long prolongation contracting with surrounding cells in the spleen. Their dynamic profiles of cytoplasmic separation were recorded by the Live Cell Imaging System. The length of telopods was mostly distributing in 20–30 μm, in accordance with normal distribution. Most telocytes had three or two telopods (28.71% and 22.58% respectively). Immunostaining indicated that these cells were positive for vimentin, CD34, nanog and sca-1, but negative for c-kit. These data prove the existence of telocytes in the spleen, which may serve as the experimental base for exploring their roles in the spleen.     

Telocytes in human skin – are they involved in skin regeneration?

Telocytes (TCs), a particular interstitial cell type, have been recently described in a wide variety of mammalian organs ( www.telocytes.com ). The TCs are identified morphologically by a small cell body and extremely long (tens to hundreds of μm), thin prolongations (less than 100 nm in diameter, below the resolving power of light microscopy) called telopodes. Here, we demonstrated with electron microscopy and immunofluorescence that TCs were present in human dermis. In particular, TCs were found in the reticular dermis, around blood vessels, in the perifollicular sheath, outside the glassy membrane and surrounding sebaceous glands, arrector pili muscles and both the secretory and excretory portions of eccrine sweat glands. Immunofluorescence screening and laser scanning confocal microscopy showed two subpopulations of dermal TCs; one expressed c‐kit/CD117 and the other was positive for CD34. Both subpopulations were also positive for vimentin. The TCs were connected to each other by homocellular junctions, and they formed an interstitial 3D network. We also found TCs adjoined to stem cells in the bulge region of hair follicles. Moreover, TCs established atypical heterocellular junctions with stem cells (clusters of undifferentiated cells). Given the frequency of allergic skin pathologies, we would like to emphasize the finding that close, planar junctions were frequently observed between TCs and mast cells. In conclusion, based on TC distribution and intercellular connections, our results suggested that TCs might be involved in skin homeostasis, skin remodelling, skin regeneration and skin repair.     

动物特络细胞的研究进展

特络细胞是一种新型间质细胞,其最显著的形态特征是具有极其细长且粗细不均而呈念珠形的细胞突起,可以和周围的同/异型细胞、血管、神经末梢等形成细胞连接。特络细胞还可释放细胞外囊泡(EVs)和其他信号分子,从而发挥其潜在的生理功能。先前的研究表明,特络细胞的功能与动物组织再生有关,因此对于低等动物特络细胞的研究有助于进一步理解其参与组织再生的机理,为人类再生医学提供参考。本文综述了近年来有关特络细胞在不同动物器官组织中的分布位置、免疫表型、超微结构特点、与周围细胞型的结构关系以及特络细胞功能的研究进展,探讨了已有研究中不同动物组织器官中特络细胞在超微结构上的差异,有助于进一步理解特络细胞的生物学特性与生理功能。     

Impairment in the telocyte/CD34+ stromal cell network in human rheumatoid arthritis synovium

Telocytes (TCs)/CD34⁺ stromal cells have recently emerged as peculiar interstitial cells detectable in a variety of organs throughout the human body. TCs are typically arranged in networks establishing unique spatial relationships with neighbour cells and likely contributing to the maintenance of tissue homeostasis by both cell-to-cell contacts and releasing extracellular vesicles. Hence, TC defects are being increasingly reported in different pathologies, such as chronic inflammatory and fibrotic conditions. In this regard, TCs/CD34⁺ stromal cells have been shown to constitute an intricate interstitial network in the subintimal area of the normal human synovial membrane, but whether they are altered in chronic synovitis has yet to be explored. We therefore undertook a morphologic study to compare the distribution of TCs/CD34⁺ stromal cells between normal synovium and chronically inflamed synovium from patients with rheumatoid arthritis (RA) by using CD34 immunohistochemistry and CD31/CD34 double immunofluorescence. CD34 immunostaining revealed that, at variance with normal synovium, the inflamed and hyperplastic RA synovial tissue was nearly or even completely devoid of TCs/CD34⁺ stromal cells. Double immunofluorescence confirmed that almost all CD34⁺ tissue components detectable in RA synovium were blood vessels coexpressing CD31, while a widespread network of CD31⁻/CD34⁺ TCs was clearly evident in the whole sublining layer of normal synovium. In the context of the emerging diverse roles of TCs/CD34⁺ stromal cells in the regulation of tissue homeostasis and structure, the remarkable impairment in their networks herein uncovered in RA synovium may suggest important pathophysiologic implications that will be worth investigating further.     

Telocytes in regenerative medicine

Telocytes (TCs) are a distinct type of interstitial cells characterized by a small cell body and extremely long and thin telopodes (Tps). The presence of TCs has been documented in many tissues and organs (go to http://www.telocytes.com ). Functionally, TCs form a three‐dimensional (3D) interstitial network by homocellular and heterocellular communication and are involved in the maintenance of tissue homeostasis. As important interstitial cells to guide or nurse putative stem and progenitor cells in stem cell niches in a spectrum of tissues and organs, TCs contribute to tissue repair and regeneration. This review focuses on the latest progresses regarding TCs in the repair and regeneration of different tissues and organs, including heart, lung, skeletal muscle, skin, meninges and choroid plexus, eye, liver, uterus and urinary system. By targeting TCs alone or in tandem with stem cells, we might promote regeneration and prevent the evolution to irreversible tissue damage. Exploring pharmacological or non‐pharmacological methods to enhance the growth of TCs would be a novel therapeutic strategy besides exogenous transplantation for many diseased disorders.     

Telocytes express PDGFRα in the human gastrointestinal tract

Telocytes (TC), a cell population located in the connective tissue of many organs of humans and laboratory mammals, are characterized by a small cell body and extremely long and thin processes. Different TC subpopulations share unique ultrastructural features, but express different markers. In the gastrointestinal (GI) tract, cells with features of TC were seen to be CD34‐positive/c‐kit‐negative and several roles have been proposed for them. Other interstitial cell types with regulatory roles described in the gut are the c‐kit‐positive/CD34‐negative/platelet‐derived growth factor receptor α (PDGFRα)‐negative interstitial cells of Cajal (ICC) and the PDGFRα‐positive/c‐kit‐negative fibroblast‐like cells (FLC). As TC display the same features and locations of the PDGFRα‐positive cells, we investigated whether TC and PDGFRα‐positive cells could be the same cell type. PDGFRα/CD34, PDGFRα/c‐kit and CD34/c‐kit double immunolabelling was performed in full‐thickness specimens from human oesophagus, stomach and small and large intestines. All TC in the mucosa, submucosa and muscle coat were PDGFRα/CD34‐positive. TC formed a three‐dimensional network in the submucosa and in the interstitium between muscle layers, and an almost continuous layer at the submucosal borders of muscularis mucosae and circular muscle layer. Moreover, TC encircled muscle bundles, nerve structures, blood vessels, funds of gastric glands and intestinal crypts. Some TC were located within the muscle bundles, displaying the same location of ICC and running intermingled with them. ICC were c‐kit‐positive and CD34/PDGFRα‐negative. In conclusion, in the human GI tract the TC are PDGFRα‐positive and, therefore, might correspond to the FLC. We also hypothesize that in human gut, there are different TC subpopulations probably playing region‐specific roles.     

Telocytes in human liver fibrosis

Liver fibrosis is a wound‐healing response which engages a variety of cell types to encapsulate injury. Telocyte (TC), a novel type of interstitial cell, has been identified in a variety of tissues and organs including liver. TCs have been reported to be reduced in fibrotic areas after myocardial infarction, human interstitial wall's fibrotic remodelling caused either by ulcerative colitis or Crohn's disease, and skin of systemic sclerosis. However, the role of TCs in human liver fibrosis remains unclear. Liver samples from human liver biopsy were collected. All samples were stained with Masson's trichrome to determine fibrosis. TCs were identified by several immunofluorescence stainings including double labelling for CD34 and c‐kit/CD117, or vimentin, or PDGF Receptor‐α, or β. We found that hepatic TCs were significantly decreased by 27%–60% in human liver fibrosis, suggesting that loss of TCs might lead to the altered organization of extracellular matrix and loss the control of fibroblast/myofibroblast activity and favour the genesis of fibrosis. Adding TCs might help to develop effective and targeted antifibrotic therapies for human liver fibrosis.     

Telocytes in liver: electron microscopic and immunofluorescent evidence

Hepatic interstitial cells play a vital role in regulating essential biological processes of the liver. Telocytes (TCs), a novel type of interstitial cells firstly identified by Popescu and his coworkers, have been reported in many tissues and organs, but not yet in liver (go to http://www.telocytes.com ). We used transmission electron microscopy and immunofluorescence (double labelling for CD34 and c‐kit/CD117, or vimentin, or PDGF Receptor‐α, or β) to provide evidence for the existence of TCs in mice liver. The distribution of TCs in liver was found to be of similar density in the four hepatic lobes. In conclusion, here we show the presence of TCs in mice liver. It remains to be determined the possible roles of TCs in the control of liver homeostasis and regeneration, the more so as a close special relationship was found between TCs and hepatic putative stem (progenitor) cells.     

Telocytes: new insight into the pathogenesis of gallstone disease

The major mechanisms of gallstone formation include biliary cholesterol hypersecretion, supersaturation and crystallization, mucus hypersecretion, gel formation and bile stasis. Gallbladder hypomotility seems to be a key event that triggers the precipitation of cholesterol microcrystals from supersaturated lithogenic bile. Telocytes, a new type of interstitial cells, have been recently identified in many organs, including gallbladder. Considering telocyte functions, it is presumed that these cells might be involved in the signalling processes. The purpose of this study was to correlate the quantity of telocytes in the gallbladder with the lithogenicity of bile. Gallbladder specimens were collected from 24 patients who underwent elective laparoscopic cholecystectomy for symptomatic gallstone disease. The control group consisted of 25 consecutive patients who received elective treatment for pancreatic head tumours. Telocytes were visualized in paraffin sections of gallbladders with double immunofluorescence using primary antibodies against c‐Kit (anti‐CD117) and anti‐mast cell tryptase. Cholesterol, phospholipid and bile acid levels were measured in gallbladder bile. The number of telocytes in the gallbladder wall was significantly lower in the study group than that in the control group (3.03 ± 1.43 versus 6.34 ± 1.66 cell/field of view in the muscularis propria, P < 0.001) and correlated with a significant increase in the cholesterol saturation index. The glycocholic and taurocholic acid levels were significantly elevated in the control subjects compared with the study group. The results suggest that bile composition may play an important role in the reduction in telocytes density in the gallbladder.     

Telocytes in liver regeneration: possible roles

Telocytes (TCs) are a novel type of interstitial cells which are potentially involved in tissue regeneration and repair ( www.telocytes.com ). Previously, we documented the presence of TCs in liver. However, the possible roles of TCs in liver regeneration remain unknown. In this study, a murine model of partial hepatectomy (PH) was used to induce liver regeneration. The number of TCs detected by double labelling immunofluorescence methods (CD34/PDGFR‐α, CD34/PDGFR‐ß and CD34/Vimentin) was significantly increased when a high level of hepatic cell proliferation rate (almost doubled) as shown by 5‐ethynyl‐2′‐deoxyuridine (EdU) immunostaining and Western Blot of Proliferating cell nuclear antigen (PCNA) was found at 48 and 72 hrs post‐PH. Meanwhile, the number of CK‐19 positive‐hepatic stem cells peaked at 72 hrs post‐PH, co‐ordinating with the same time‐point, when the number of TCs was most significantly increased. Taken together, the results indicate a close relationship between TCs and the cells essentially involved in liver regeneration: hepatocytes and stem cells. It remains to be determined how TCs affect hepatocytes proliferation and/or hepatic stem cell differentiation in liver regeneration. Besides intercellular junctions, we may speculate a paracrine effect via ectovesicles.     

Telocytes are the physiological counterpart of inflammatory fibroid polyps and PDGFRA‐mutant GISTs

PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been identified as a physiological counterpart of the latter, while interstitial Cajal cells (ICC) are considered the precursor of the former. However, ICC hyperplasia (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been identified in germline KIT‐mutant settings but not in PDGFRA‐mutant ones, challenging the precursor role of ICC for PDGFRA‐driven GISTs. Telocytes are a recently described interstitial cell type, CD34+/PDGFRA+. Formerly considered fibroblasts, they are found in many organs, including the GI tract where they are thought to be involved in neurotransmission. Alongside IFPs and gastric GISTs, GI wall “fibrosis” has been reported in germline PDGFRA‐mutants. Taking the opportunity offered by its presence in a germline PDGFRA‐mutant individual, we demonstrate that this lesion is sustained by hyperplastic telocytes, constituting the PDGFRA‐mutant counterpart of germline KIT mutation‐associated ICCH. Moreover, our findings support a pathogenetic relationship between telocyte hyperplasia and both IFPs and PDGFRA‐mutant GISTs. We propose the term “telocytoma” for defining IFP, as it conveys both the pathogenetic (neoplastic) and histotypic (“telocytary”) essence of this tumour, unlike IFP, which rather evokes an inflammatory‐hyperplastic lesion.