Correspondence on ‘Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement’

Manetti, Mirko

doi:10.1136/annrheumdis-2020-219264

Cited by 3 publications

(5 citation statements)

References 10 publications

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“…Indeed, in multiple processes, including repair, tumor stroma formation, diabetes, fibrosis and systemic sclerosis, the presence or absence of CD34+SCs/TCs plays an important role. Examples include some malignant neoplasms and systemic sclerosis, in which derangement of the microvascular system occurs [ 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 ]. In addition to lipofibroblasts and myofibroblasts, CD34+SCs/TCs can be a source of lipoblasts, chondroblasts, and osteoblasts.…”

Section: Cd34+scs/tcs In Sprouting Angiogenesismentioning

confidence: 99%

Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis

Gutiérrez

García

González‐Gómez

et al. 2022

IJMS

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Perivascular cells in the pericytic microvasculature, pericytes and CD34+ stromal cells/telocytes (CD34+SCs/TCs), have an important role in angiogenesis. We compare the behavior of these cells depending on whether the growth of endothelial cells (ECs) from the pre-existing microvasculature is toward the interstitium with vascular bud and neovessel formation (sprouting angiogenesis) or toward the vascular lumen with intravascular pillar development and vessel division (intussusceptive angiogenesis). Detachment from the vascular wall, mobilization, proliferation, recruitment, and differentiation of pericytes and CD34+SCs/TCs, as well as associated changes in vessel permeability and functionality, and modifications of the extracellular matrix are more intense, longer lasting over time, and with a greater energy cost in sprouting angiogenesis than in intussusceptive angiogenesis, in which some of the aforementioned events do not occur or are compensated for by others (e.g., sparse EC and pericyte proliferation by cell elongation and thinning). The governing mechanisms involve cell–cell contacts (e.g., peg-and-socket junctions between pericytes and ECs), multiple autocrine and paracrine signaling molecules and pathways (e.g., vascular endothelial growth factor, platelet-derived growth factor, angiopoietins, transforming growth factor B, ephrins, semaphorins, and metalloproteinases), and other factors (e.g., hypoxia, vascular patency, and blood flow). Pericytes participate in vessel development, stabilization, maturation and regression in sprouting angiogenesis, and in interstitial tissue structure formation of the pillar core in intussusceptive angiogenesis. In sprouting angiogenesis, proliferating perivascular CD34+SCs/TCs are an important source of stromal cells during repair through granulation tissue formation and of cancer-associated fibroblasts (CAFs) in tumors. Conversely, CD34+SCs/TCs have less participation as precursor cells in intussusceptive angiogenesis. The dysfunction of these mechanisms is involved in several diseases, including neoplasms, with therapeutic implications.

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Section: Cd34+scs/tcs In Sprouting Angiogenesismentioning

confidence: 99%

Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis

Gutiérrez

García

González‐Gómez

et al. 2022

IJMS

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“…The behavior of CD34+SCs/TCs in most non-tumoral diseases of the skin has received little attention. Exceptions are psoriasis, scleroderma (systemic sclerosis), and wound healing on which several studies have been published [ 38 , 45 , 47 , 48 , 49 , 56 , 57 , 58 , 59 , 60 ]. We will first consider the non-tumoral pathological processes in which CD34+SCs/TCs have important pathophysiological implications, mainly related to the role of CD34+SCs/TCs in tissue homeostasis, control and organization of the extracellular matrix, and regeneration and repair.…”

Section: Cd34+scs In Non-tumoral Pathological Skinmentioning

confidence: 99%

“…The purpose was to obtain a comprehensive outline, without making the work overly long. Although there are important studies on the behavior of CD34+SCs/TCs in non-tumoral pathological processes of the skin, such as systemic fibrosis [ 38 , 47 , 48 , 56 , 57 , 58 , 59 , 60 , 61 ] and psoriasis [ 49 ], this is not the case for most non-tumoral pathological processes.…”

Section: General Considerations and Required Future Studies About Cd34+scs/tcs In Normal And Pathological Skinmentioning

confidence: 99%

“…The participation of CD34+SCs/TCs in the organization of the extracellular matrix explains the important role of these cells in fibrosing/sclerosing diseases—as the Italian school has demonstrated in systemic sclerosis (scleroderma) [ 38 , 47 , 48 , 56 , 57 , 58 , 59 , 60 , 61 ]—as well as in the basophilic degeneration of collagen and mucinosis. In scleroderma, we show the coexpression of CD34 and αSMA in some stromal cells, which suggests the participation of CD34+SCs/TCs as a source of myofibroblasts in this lesion.…”

Section: General Considerations and Required Future Studies About Cd34+scs/tcs In Normal And Pathological Skinmentioning

confidence: 99%

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Cd34+ Stromal Cells/Telocytes in Normal and Pathological Skin

Gutiérrez

García

González‐Gómez

et al. 2021

IJMS

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We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other authors in the normal dermis regarding CD34+SC/TC characteristics and distribution around vessels, nerves and cutaneous annexes, highlighting their practical absence in the papillary dermis and presence in the bulge region of perifollicular groups of very small CD34+ stromal cells. In non-tumoral skin pathology, we studied examples of the principal histologic patterns in which CD34+SCs/TCs have (1) a fundamental pathophysiological role, including (a) fibrosing/sclerosing diseases, such as systemic sclerosis, with loss of CD34+SCs/TCs and presence of stromal cells co-expressing CD34 and αSMA, and (b) metabolic degenerative processes, including basophilic degeneration of collagen, with stromal cells/telocytes in close association with degenerative fibrils, and cutaneous myxoid cysts with spindle-shaped, stellate and bulky vacuolated CD34+ stromal cells, and (2) a secondary reactive role, encompassing dermatitis—e.g., interface (erythema multiforme), acantholytic (pemphigus, Hailey–Hailey disease), lichenoid (lichen planus), subepidermal vesicular (bullous pemphigoid), psoriasiform (psoriasis), granulomatous (granuloma annulare)—vasculitis (leukocytoclastic and lymphocytic vasculitis), folliculitis, perifolliculitis and inflammation of the sweat and sebaceous glands (perifolliculitis and rosacea) and infectious dermatitis (verruca vulgaris). In skin tumor and tumor-like conditions, we studied examples of those in which CD34+ stromal cells are (1) the neoplastic component (dermatofibrosarcoma protuberans, sclerotic fibroma and solitary fibrous tumor), (2) a neoplastic component with varying presentation (fibroepithelial polyp and superficial myxofibrosarcoma) and (3) a reactive component in other tumor/tumor-like cell lines, such as those deriving from vessel periendothelial cells (myopericytoma), epithelial cells (trichoepithelioma, nevus sebaceous of Jadassohn and seborrheic keratosis), Merkel cells (Merkel cell carcinoma), melanocytes (dermal melanocytic nevi) and Schwann cells (neurofibroma and granular cell tumor).

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“…We thank Dr Manetti for his comments regarding the distinctive CD34 positive dermal stromal cell population and their pathological changes in systemic sclerosis (SSc) skin. [1][2][3][4] One challenge for the field of SSc dermatopathology is a lack of broad consensus regarding the terminology used to describe CD34+ cells. 5 Indeed, CD34+ cells have been described as fibrocytes, 6 stromal fibroblastic cells, 7 dermal dendritic cells, 8 fibroblasts 5 9-11 and telocytes.…”

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confidence: 99%

Response to: ‘Correspondence on ‘Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement’’ by Manetti

et al. 2020

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Correspondence on ‘Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement’

Abstract: Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Cited by 3 publications

References 10 publications

Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis

Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis

Cd34+ Stromal Cells/Telocytes in Normal and Pathological Skin

Response to: ‘Correspondence on ‘Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement’’ by Manetti

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