Telocytes in the Normal and Pathological Peripheral Nervous System

Díaz‐Flores, Lucio; Gutiérrez, Ricardo; García, Ma Pino; Gayoso, Sara; Gutiérrez, Emma Virginia García; Carrasco, José Luís

doi:10.3390/ijms21124320

Cited by 26 publications

(51 citation statements)

References 103 publications

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“…In a previous review on TCs/CD34+SCs in the peripheral nervous system, we highlighted the behaviour of these cells in neuropathies of the appendix and gallbladder [ 43 ]. Using confocal microscopy, we then studied the involvement of adipose tissue in appendicular hyperplastic neurogenic processes.…”

Section: Tcs/cd34+scs In Pathologically Affected Adipose Tissuementioning

confidence: 99%

Telocytes/CD34+ Stromal Cells in Pathologically Affected White Adipose Tissue

Díaz‐Flores

Gutiérrez

García

et al. 2020

IJMS

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We studied telocytes/CD34+ stromal cells (TCs/CD34+SCs) in pathologically affected white adipose tissue after briefly examining them in normal fat. To this aim, we reviewed pathological processes, including original contributions, in which TCs/CD34+SCs are conserved, increased, and lost, or acquire a specific arrangement. The pathologic processes in which TCs/CD34+SCs are studied in adipose tissue include inflammation and repair through granulation tissue, iatrogenic insulin-amyloid type amyloidosis, non-adipose tissue components (nerve fascicles and fibres in neuromas and hyperplastic neurogenic processes) and tumours (signet ring carcinoma with Krukenberg tumour and colon carcinoma) growing in adipose tissue, adipose tissue tumours (spindle cell lipoma, dendritic fibromyxolipoma, pleomorphic lipoma, infiltrating angiolipoma of skeletal muscle and elastofibrolipoma), lipomatous hypertrophy of the interatrial septum, nevus lipomatosus cutaneous superficialis of Hoffman–Zurhelle and irradiated adipose tissue of the perirectal and thymic regions. Two highly interesting issues emerged: (1) whether the loss of CD34 expression in TCs/CD34+SCs is by changes in marker expression or the disappearance of these cells (the findings suggest the first possibility) and (2) whether in some invasive and metastatic malignant tumours, TCs/CD34+SCs that completely surround neoplastic cells act as nurse and/or isolating cells. Further studies are required on adipose tissue TCs/CD34+SCs, mainly in lipomatosis and obesity.

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Section: Tcs/cd34+scs In Pathologically Affected Adipose Tissuementioning

confidence: 99%

Telocytes/CD34+ Stromal Cells in Pathologically Affected White Adipose Tissue

Díaz‐Flores

Gutiérrez

García

et al. 2020

IJMS

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“…Fibroblasts are another important cell type in peripheral nerves; they are the most abundant cells in the endoneurium, perineurium and epineurium and provide structural support, regional separation and protection of nerve fibers from damage (Parrinello et al, 2010 ; Stierli et al, 2018 ; Carr et al, 2019 ; Diaz-Flores et al, 2020 ). They have mesenchymal cell properties and play an important role in nerve repair following injury (Parrinello et al, 2010 ; Carr et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…They have mesenchymal cell properties and play an important role in nerve repair following injury (Parrinello et al, 2010 ; Carr et al, 2019 ). We tested marker genes for fibroblasts reported in previous mouse sciatic nerve scRNA-seq studies including: Sfrp4, Pi16, Dpt, Gsn, Col1a1, Col1a2, Col3a1, Col14a1, Clec3b, Cygb, Prrx1, and Aebp1 (Carr et al, 2019 ; Diaz-Flores et al, 2020 ; Toma et al, 2020 ; Wolbert et al, 2020 ). We found that some of these genes are not fibroblast-specific and that while some of them were fibroblast specific, they only label one sub-population of epineurial, perineurial or endoneurial fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…According to the anatomical location, peripheral nerve fibroblasts could be divided into endoneurial, perineurial and epineurial fibroblasts (Osawa and Ide, 1986 ; Pina-Oviedo and Ortiz-Hidalgo, 2008 ). Endoneurial fibroblasts are spindle-shaped cells with long processes making contact with other cell types in the endoneurium, they are present between nerve fibers and compose 12.5% of all endoneurial cells (Stierli et al, 2018 ; Carr et al, 2019 ; Diaz-Flores et al, 2020 ). Endoneurial fibroblasts have also been named as tactocytes (Stierli et al, 2018 ), endoneurial mesenchymal cells (Carr et al, 2019 ) and endoneurial telocytes (Diaz-Flores et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration

Chen

Banton

Singh

et al. 2021

Front. Cell. Neurosci.

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The advances in single-cell RNA sequencing technologies and the development of bioinformatics pipelines enable us to more accurately define the heterogeneity of cell types in a selected tissue. In this report, we re-analyzed recently published single-cell RNA sequencing data sets and provide a rationale to redefine the heterogeneity of cells in both intact and injured mouse peripheral nerves. Our analysis showed that, in both intact and injured peripheral nerves, cells could be functionally classified into four categories: Schwann cells, nerve fibroblasts, immune cells, and cells associated with blood vessels. Nerve fibroblasts could be sub-clustered into epineurial, perineurial, and endoneurial fibroblasts. Identified immune cell clusters include macrophages, mast cells, natural killer cells, T and B lymphocytes as well as an unreported cluster of neutrophils. Cells associated with blood vessels include endothelial cells, vascular smooth muscle cells, and pericytes. We show that endothelial cells in the intact mouse sciatic nerve have three sub-types: epineurial, endoneurial, and lymphatic endothelial cells. Analysis of cell type-specific gene changes revealed that Schwann cells and endoneurial fibroblasts are the two most important cell types promoting peripheral nerve regeneration. Analysis of communication between these cells identified potential signals for early blood vessel regeneration, neutrophil recruitment of macrophages, and macrophages activating Schwann cells. Through this analysis, we also report appropriate marker genes for future single cell transcriptome data analysis to identify cell types in intact and injured peripheral nerves. The findings from our analysis could facilitate a better understanding of cell biology of peripheral nerves in homeostasis, regeneration, and disease.

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“…Given the extensive distribution of TC interstitial networks in different organs and the numerous putative roles attributed to these stromal cells, increasing literature has hypothesized that their phenotypic and functional alterations may be implicated in different pathologic conditions [ 28 , 29 , 30 , 31 ]. Indeed, recent studies have reported a reduction in TCs and severe structural changes in the TC stromal network in a variety of disorders, including heart failure and conditions characterized by chronic tissue inflammation and/or fibrotic remodeling, such as psoriasis, primary Sjögren’s syndrome, Crohn’s disease, ulcerative colitis, systemic sclerosis, and liver fibrosis [ 24 , 28 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

A Two-Step Immunomagnetic Microbead-Based Method for the Isolation of Human Primary Skin Telocytes/CD34+ Stromal Cells

Romano

Rosa

Fioretto

et al. 2020

IJMS

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Telocytes (TCs), commonly referred to as TCs/CD34+ stromal cells, are a peculiar type of interstitial cells with distinctive morphologic traits that are supposed to exert several biological functions, including tissue homeostasis regulation, cell-to-cell signaling, immune surveillance, and reparative/regenerative effects. At present, the majority of studies investigating these cells are mainly descriptive and focus only on their morphology, with a consequent paucity of functional data. To gain relevant insight into the possible functions of TCs, in vitro analyses are clearly required, but currently, the protocols for TC isolation are only at the early stages and not fully standardized. In the present in vitro study, we describe a novel methodology for the purification of human primary skin TCs through a two-step immunomagnetic microbead-based cell separation (i.e., negative selection for CD31 followed by positive selection for CD34) capable of discriminating these cells from other connective tissue-resident cells on the basis of their different immunophenotypic features. Our experiments clearly demonstrated that the proposed method allows a selective purification of cells exhibiting the peculiar TC morphology. Isolated TCs displayed very long cytoplasmic extensions with a moniliform silhouette (telopodes) and presented an immunophenotypic profile (CD31−/CD34+/PDGFRα+/vimentin+) that unequivocally differentiates them from endothelial cells (CD31+/CD34+/PDGFRα−/vimentin+) and fibroblasts (CD31−/CD34−/PDGFRα+/vimentin+). This novel methodology for the isolation of TCs lays the groundwork for further research aimed at elucidating their functional properties and possible translational applications, especially in the field of regenerative medicine.

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Telocytes in the Normal and Pathological Peripheral Nervous System

Cited by 26 publications

References 103 publications

Telocytes/CD34+ Stromal Cells in Pathologically Affected White Adipose Tissue

Telocytes/CD34+ Stromal Cells in Pathologically Affected White Adipose Tissue

Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration

A Two-Step Immunomagnetic Microbead-Based Method for the Isolation of Human Primary Skin Telocytes/CD34+ Stromal Cells

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