scholarly journals Mesenchymal Stem/Stromal Cells and Fibroblasts: Their Roles in Tissue Injury and Regeneration, and Age-Related Degeneration

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.

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 968
Author(s):  
Yousra Hamdan ◽  
Loubna Mazini ◽  
Gabriel Malka

Exosomes are the main actors of intercellular communications and have gained great interest in the new cell-free regenerative medicine. These nanoparticles are secreted by almost all cell types and contain lipids, cytokines, growth factors, messenger RNA, and different non-coding RNA, especially micro-RNAs (mi-RNAs). Exosomes’ cargo is released in the neighboring microenvironment but is also expected to act on distant tissues or organs. Different biological processes such as cell development, growth and repair, senescence, migration, immunomodulation, and aging, among others, are mediated by exosomes and principally exosome-derived mi-RNAs. Moreover, their therapeutic potential has been proved and reinforced by their use as biomarkers for disease diagnostics and progression. Evidence has increasingly shown that exosome-derived mi-RNAs are key regulators of age-related diseases, and their involvement in longevity is becoming a promising issue. For instance, mi-RNAs such as mi-RNA-21, mi-RNA-29, and mi-RNA-34 modulate tissue functionality and regeneration by targeting different tissues and involving different pathways but might also interfere with long life expectancy. Human mi-RNAs profiling is effectively related to the biological fluids that are reported differently between young and old individuals. However, their underlying mechanisms modulating cell senescence and aging are still not fully understood, and little was reported on the involvement of mi-RNAs in cell or tissue longevity. In this review, we summarize exosome biogenesis and mi-RNA synthesis and loading mechanism into exosomes’ cargo. Additionally, we highlight the molecular mechanisms of exosomes and exosome-derived mi-RNA regulation in the different aging processes.


2021 ◽  
Vol 22 (4) ◽  
pp. 1920
Author(s):  
Federica Marzano ◽  
Antonio Rapacciuolo ◽  
Nicola Ferrara ◽  
Giuseppe Rengo ◽  
Walter J. Koch ◽  
...  

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors and they are responsible for the transduction of extracellular signals, regulating almost all aspects of mammalian physiology. These receptors are specifically regulated by a family of serine/threonine kinases, called GPCR kinases (GRKs). Given the biological role of GPCRs, it is not surprising that GRKs are also involved in several pathophysiological processes. Particular importance is emerging for GRK5, which is a multifunctional protein, expressed in different cell types, and it has been found located in single or multiple subcellular compartments. For instance, when anchored to the plasma membrane, GRK5 exerts its canonical function, regulating GPCRs. However, under certain conditions (e.g., pro-hypertrophic stimuli), GRK5 translocates to the nucleus of cells where it can interact with non-GPCR-related proteins as well as DNA itself to promote “non-canonical” signaling, including gene transcription. Importantly, due to these actions, several studies have demonstrated that GRK5 has a pivotal role in the pathogenesis of chronic-degenerative disorders. This is true in the cardiac cells, tumor cells, and neurons. For this reason, in this review article, we will inform the readers of the most recent evidence that supports the importance of targeting GRK5 to prevent the development or progression of cancer, cardiovascular, and neurological diseases.


2006 ◽  
Vol 27 (7) ◽  
pp. 762-778 ◽  
Author(s):  
Maria E. Trujillo ◽  
Philipp E. Scherer

The endocrine functions of the adipose organ are widely studied at this stage. The adipose organ, and in particular adipocytes, communicate with almost all other organs. Although some adipose tissue pads assume the functions as distinct “miniorgans,” adipocytes can also be present in smaller numbers interspersed with other cell types. Although fat pads have the potential to have a significant systemic impact, adipocytes may also affect neighboring tissues through paracrine interactions. These local or systemic effects are mediated through lipid and protein factors. The protein factors are commonly referred to as adipokines. Their expression and posttranslational modifications can undergo dramatic changes under different metabolic conditions. Due to the fact that none of the mutations that affect adipose tissue trigger embryonic lethality, the study of adipose tissue physiology lends itself to genetic analysis in mice. In fact, life in the complete absence of adipose tissue is possible in a laboratory setting, making even the most extreme adipose tissue phenotypes genetically amenable to be analyzed by disruption of specific genes or overexpression of others. Here, we briefly discuss some basic aspects of adipocyte physiology and the systemic impact of adipocyte-derived factors on energy homeostasis.


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.


Eye ◽  
2022 ◽  
Author(s):  
Nicholas D. Nolan ◽  
Salvatore M. Caruso ◽  
Xuan Cui ◽  
Stephen H. Tsang

AbstractRetinitis pigmentosa is characterized by a dysregulation within the metabolic coupling of the retina, particularly between the glycolytic photoreceptors and the oxidative retina pigment epithelium. This phenomenon of metabolic uncoupling is seen in both aging and retinal degenerative diseases, as well as across a variety of cell types in human biology. Given its crucial role in the health and maintenance of these cell types, the metabolic pathways involved present a suitable area for therapeutic intervention. Herein, this review covers the scope of this delicate metabolic interplay, its dysregulation, how it relates to the retina as well other cell types, and finally concludes with a summary of various strategies aimed at reinstating normal metabolic coupling within the retina, and future directions within the field.


Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 225 ◽  
Author(s):  
Irène Tatischeff

Cell-derived extracellular vesicles (EVs) are newly uncovered messengers for intercellular communication. They are released by almost all cell types in the three kingdoms, Archeabacteria, Bacteria and Eukaryotes. They are known to mediate important biological functions and to be increasingly involved in cell physiology and in many human diseases, especially in oncology. The aim of this review is to recapitulate the current knowledge about EVs and to summarize our pioneering work about Dictyostelium discoideum EVs. However, many challenges remain unsolved in the EV research field, before any EV application for theranostics (diagnosis, prognosis, and therapy) of human cancers, can be efficiently implemented in the clinics. Dictyostelium might be an outstanding eukaryotic cell model for deciphering the utmost challenging problem of EV heterogeneity, and for unraveling the still mostly unknown mechanisms of their specific functions as mediators of intercellular communication.


2020 ◽  
Author(s):  
Ioanna Sevastou ◽  
Ioanna Ninou ◽  
Vassilis Aidinis

AbstractAutotaxin (ATX) is secreted by various type of cells in health and disease and catalyzes the extracellular production of lysophosphatidic acid (LPA). In turn, LPA is a bioactive lysophospholipid promoting a wide array of cellular functions through its multiple G-protein coupled receptors, differentially expressed in almost all cell types. ATX expression has been shown necessary for embryonic development and has been suggested to participate in the pathogenesis of different chronic inflammatory diseases and cancer. Deregulated ATX and LPA levels have been reported in multiple sclerosis (MS) and its experimental model, experimental autoimmune encephalomyelitis (EAE). ATX genetic deletion from macrophages and microglia (CD11b+ cells) attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in MS/EAE. In this report, increased ATX staining was localized to glial fibrillary acidic protein positive (GFAP+) cells, mostly astrocytes, in spinal cord sections from EAE mice at the peak of the disease. However, genetic deletion of ATX from GFAP+ cells resulted in embryonic lethality, suggesting a major role for ΑΤΧ expression from GFAP+ cells in embryonic development, that urges further dissection. Moreover, the re-expression of ATX from GFAP+ cells during the pathogenesis of EAE, reinforces the concept that ATX/LPA is a developmental program aberrantly reactivated upon chronic inflammation.


2019 ◽  
Vol 72 (8) ◽  
pp. 1473-1476
Author(s):  
Nataliya Matolinets ◽  
Helen Sklyarova ◽  
Eugene Sklyarov ◽  
Andrii Netliukh

Introduction: Polytrauma patients have high risk of shock, septic complications and death during few years of follow-up. In recent years a lot of attention is paid to gaseous transmitters, among which are nitrogen oxide (NO) and hydrogen sulfide (H2S). It is known that the rise of NO and its metabolites levels occurs during the acute period of polytrauma. Nitric oxide and hydrogen sulfide are produced in different cell types, among which are lymphocytes. The aim: To investigate the levels of NO, NOS, iNOS, еNOS, H2S in lymphocytes lysate in patients at the moment of hospitalization and 24 hours after trauma. Materials and methods: We investigated the levels of NO, NO-synthase, inducible NO-synthase, endothelial NO-synthase, H2S in lymphocytes lysate in patients at the moment of hospitalization and 24 hours after trauma. Results: The study included 20 patients with polytrauma who were treated in the intensive care unit (ICU) of the Lviv Emergency Hospital. Tissue injury was associated with an increased production of NO, NOS, iNOS, еNOS during the acute period of polytrauma. At the same time, the level of H2S decreased by the end of the first day of traumatic injury. Conclusions: In acute period of polytrauma, significant increasing of iNOS and eNOS occurs with percentage prevalence of iNOS over eNOS on the background of H2S decreasing.


2020 ◽  
Vol 27 (29) ◽  
pp. 4840-4854 ◽  
Author(s):  
Chrysoula-Evangelia Karachaliou ◽  
Hubert Kalbacher ◽  
Wolfgang Voelter ◽  
Ourania E. Tsitsilonis ◽  
Evangelia Livaniou

Prothymosin alpha (ProTα) is a highly acidic polypeptide, ubiquitously expressed in almost all mammalian cells and tissues and consisting of 109 amino acids in humans. ProTα is known to act both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similar to molecules termed as “alarmins”. Antibodies and immunochemical techniques for ProTα have played a leading role in the investigation of the biological role of ProTα, several aspects of which still remain unknown and contributed to unraveling the diagnostic and therapeutic potential of the polypeptide. This review deals with the so far reported antibodies along with the related immunodetection methodology for ProTα (immunoassays as well as immunohistochemical, immunocytological, immunoblotting, and immunoprecipitation techniques) and its application to biological samples of interest (tissue extracts and sections, cells, cell lysates and cell culture supernatants, body fluids), in health and disease states. In this context, literature information is critically discussed, and some concluding remarks are presented.


Author(s):  
Monika Lewandowska ◽  
Rafał Milner ◽  
Małgorzata Ganc ◽  
Elżbieta Włodarczyk ◽  
Joanna Dołżycka ◽  
...  

AbstractThere are discrepancies in the literature regarding the course of central auditory processes (CAP) maturation in typically developing children and adolescents. The purpose of the study was to provide an overview of age – related improvement in CAP in Polish primary and secondary school students aged 7–16 years. 180 children/adolescents, subdivided into 9 age categories, and 20 adults (aged 18–24 years) performed the Dichotic Digit Test (DDT), Duration Pattern Test (DPT), Frequency Pattern Test (FPT), Gap Detection Test (GDT) and adaptive Speech-in-Noise (aSpN). The 12-year-olds was retested after w week. We found the age effects only for the DDT, DPT and FPT. In the right ear DDT the 7-year-olds performed more poorly than all groups ≥12. In the left ear DDT both 7- and 8-year-olds achieved less correct responses compared with the 13-, 14-, 15-year-olds and with the adults. The right ear advantage was greater in the 7-year-olds than in the 15-year-olds and adult group. At the age of 7 there was lower DPT and FPT scores than in all participants ≥13 whereas the 8-year-olds obtained less correct responses in the FPT than all age categories ≥12. Almost all groups (except for the 7-year-olds) performed better in the DPT than FPT. The test-retest reliability for all tests was satisfactory. The study demonstrated that different CAP have their own patterns of improvement with age and some of them are specific for the Polish population. The psychoacoustic battery may be useful in screening for CAP disorders in Poland.


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