Stromal cells in health and disease

2018 ◽  
Vol 93 (9) ◽  
pp. 871-875 ◽  
Author(s):  
Frank A. Schildberg ◽  
Vera S. Donnenberg
2021 ◽  
Vol 22 (24) ◽  
pp. 13422
Author(s):  
Mirko Manetti

The term “stromal cells” refers to a highly heterogeneous class of connective tissue cells that build the infrastructure of any organ and fulfill a variety of fundamental roles in health and disease [...]


Author(s):  
C. Grasso ◽  
C. Pierie ◽  
R.E. Mebius ◽  
L.G.M. van Baarsen

2021 ◽  
Author(s):  
Amro A. Hussien ◽  
Barbara Niederoest ◽  
Maja Bollhalder ◽  
Nils Goedecke ◽  
Jess G. Snedeker

Matrix stiffness and its effects on tensional homeostasis act as major regulators of cellular states in health and disease. Stiffness-sensing studies are typically performed using cells that have acquired "mechanical memory" through prolonged propagation in rigid mechanical environments, e.g. tissue culture plastic (TCP). This may potentially mask the full extent of the stiffness-driven mechanosensing programs. To address this, we developed a biomaterial system composed of two-dimensional mechano-variant silicone substrates that is permissive to large-scale cell culture expansion processes. We broadly mapped the stiffness-mediated mechano-responses by performing RNA sequencing on human tendon-derived stromal cells. We find that matrix rigidities approximating tendon microscale stiffness range (E. ~35 kPa) distinctly favor programs related to chromatin remodeling and Hippo signaling; whereas more compliant stiffnesses (E. 2 kPa) were enriched in responses related to pluripotency, synapse assembly and angiogenesis. We also find that tendon stromal cells undergo dramatic phenotypic drift on conventional TCP, with near-complete suppression of tendon-related genes and emergence of expression signatures skewed towards fibro-inflammatory and metabolic activation. Strikingly, mechano-variant substrates abrogate fibroblasts activation, with tenogenic stiffnesses inducing a transcriptional program that strongly correlate with established tendon tissue-specific signatures. Computational inference predicted that AKT1 and ERK1/2 are major signaling hubs mediating stiffness-sensing in tendon cells. Together, our findings highlight how the underlying biophysical cues may dictate the transcriptional identity of resident cells, and how matrix mechano-reciprocity regulates diverse sets of previously underappreciated mechanosensitive processes in tendon stromal fibroblasts.


2022 ◽  
Vol 12 ◽  
Author(s):  
Ricardo Melo Ferreira ◽  
Benjamin J. Freije ◽  
Michael T. Eadon

The kidney is composed of heterogeneous groups of epithelial, endothelial, immune, and stromal cells, all in close anatomic proximity. Spatial transcriptomic technologies allow the interrogation of in situ expression signatures in health and disease, overlaid upon a histologic image. However, some spatial gene expression platforms have not yet reached single-cell resolution. As such, deconvolution of spatial transcriptomic spots is important to understand the proportion of cell signature arising from these varied cell types in each spot. This article reviews the various deconvolution strategies discussed in the 2021 Indiana O’Brien Center for Microscopy workshop. The unique features of Seurat transfer score methodology, SPOTlight, Robust Cell Type Decomposition, and BayesSpace are reviewed. The application of normalization and batch effect correction across spatial transcriptomic samples is also discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Alice Pievani ◽  
Roberto Savoldelli ◽  
Juliane Poelchen ◽  
Elisa Mattioli ◽  
Giorgio Anselmi ◽  
...  

Tissue engineering opens multiple opportunities in regenerative medicine, drug testing, and modeling of the hematopoiesis in health and disease. Recapitulating the organization of physiological microenvironments supporting leukocyte development is essential to model faithfully the development of immune cells. Hematopoietic organs are shaped by spatially organized niches defined by multiple cellular contributions. A shared feature of immune niches is the presence of mesenchymal stromal cells endowed with unique roles in organizing niche development, maintenance, and function. Here, we review challenges and opportunities in harnessing stromal cells for the engineering of artificial immune niches and hematopoietic organoids recapitulating leukocyte ontogeny both in vitro and in vivo.


2021 ◽  
Author(s):  
Janja Zupan

Mesenchymal stem/stromal cells (MSCs) and fibroblasts are present in normal tissues to support tissue homeostasis. Both share common pathways and have a number of common features, such as a spindle-shaped morphology, connective tissue localization, and multipotency. In inflammation, a nonspecific response to injury, fibroblasts and MSC are the main players.Two mechanisms of their mode of action have been defined: immunomodulation and regeneration. Following tissue injury, MSCs are activated, and they multiply and differentiate, to mitigate the damage. With aging and, in particular, in degenerative disorders of the musculoskeletal system (i.e., joint and bone disorders), the regenerative capacity of MSCs appears to be lost or diverted into the production of other nonfunctional cell types, such as adipocytes and fibroblasts. Fibroblasts are stromal cells that provide the majority of the structural framework of almost all types of tissues; i.e., the stroma. As such, fibroblasts also have significant roles in tissue development, maintenance, and repair. In their immunosuppressive role, MSCs and fibroblasts contribute to the normal resolution of inflammation that is a prerequisite for successful tissue repair. In this chapter, we review the common and opposing properties of different tissue-derived MSCs and fibroblasts under physiological and pathophysiological conditions. We consider injury and age-related degeneration of various tissues, and also some immunological disorders. Specifically, we address the distinct and common features of both cell types in health and disease, with a focus on human synovial joints. Finally, we also discuss the possible approaches to boost the complementary roles of MSCs and fibroblasts, to promote successful tissue regeneration.


2012 ◽  
Vol 213 (2) ◽  
pp. 123-141 ◽  
Author(s):  
G Burnstock ◽  
I Novak

Pancreatic cells contain specialised stores for ATP. Purinergic receptors (P2 and P1) and ecto-nucleotidases are expressed in both endocrine and exocrine calls, as well as in stromal cells. The pancreas, especially the endocrine cells, were an early target for the actions of ATP. After the historical perspective of purinergic signalling in the pancreas, the focus of this review will be the physiological functions of purinergic signalling in the regulation of both endocrine and exocrine pancreas. Next, we will consider possible interaction between purinergic signalling and other regulatory systems and their relation to nutrient homeostasis and cell survival. The pancreas is an organ exhibiting several serious diseases – cystic fibrosis, pancreatitis, pancreatic cancer and diabetes – and some are associated with changes in life-style and are increasing in incidence. There is upcoming evidence for the role of purinergic signalling in the pathophysiology of the pancreas, and the new challenge is to understand how it is integrated with other pathological processes.


2016 ◽  
Vol 310 (9) ◽  
pp. G696-G704 ◽  
Author(s):  
Liyi Wang ◽  
Islay Steele ◽  
Jothi Dinesh Kumar ◽  
Rod Dimaline ◽  
Puthen V. Jithesh ◽  
...  

Stromal cells influence epithelial function in both health and disease. Myofibroblasts are abundant stromal cells that influence the cellular microenvironment by release of extracellular matrix (ECM) proteins, growth factors, proteases, cytokines, and chemokines. Cancer-associated myofibroblasts (CAMs) differ from adjacent tissue (ATMs) and normal tissue myofibroblasts (NTMs), but the basis of this is incompletely understood. We report now the differential expression of miRNAs in gastric cancer CAMs. MicroRNA arrays identified differences in the miRNA profile in gastric and esophageal NTMs and in CAMs from stomach compared with NTMs. miR-181d was upregulated in gastric CAMs. Analysis of differentially regulated miRNAs indicated an involvement in Wnt signaling. Examination of a microarray data set then identified Wnt5a as the only consistently upregulated Wnt ligand in gastric CAMs. Wnt5a stimulated miR-181d expression, and knockdown of miR-181d inhibited Wnt5a stimulation of CAM proliferation and migration. Analysis of miR-181d targets suggested a role in chemotaxis. Conditioned medium from CAMs stimulated gastric cancer cell (AGS) migration more than that from ATMs, and miR-181d knockdown reduced the effect of CAM-CM on AGS cell migration but had no effect on AGS cell responses to ATM conditioned media. The data suggest that dysregulation of miRNA expression in gastric CAMs, secondary to Wnt5a signaling, accounts at least in part for the effect of CAMs in promoting cancer cell migration.


2005 ◽  
Vol 5 (7) ◽  
pp. 723-732 ◽  
Author(s):  
Mari Dezawa ◽  
Mikio Hoshino ◽  
Yo-ichi Nabeshima ◽  
Chizuka Ide

Author(s):  
Sarah A. Luse

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.


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