scholarly journals Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Marine Theret ◽  
Fabio M. V. Rossi ◽  
Osvaldo Contreras
Keyword(s):  
Stromal Cells ◽  
Current Knowledge ◽  
Neuromuscular Disorders ◽  
Significant Proportion ◽  
Muscle Disease ◽  
Tissue Degeneration ◽  
Muscle Trauma ◽  
Muscle Homeostasis ◽  
Activated Fibroblasts ◽  
And Behavior

Normal skeletal muscle functions are affected following trauma, chronic diseases, inherited neuromuscular disorders, aging, and cachexia, hampering the daily activities and quality of life of the affected patients. The maladaptive accumulation of fibrous intramuscular connective tissue and fat are hallmarks of multiple pathologies where chronic damage and inflammation are not resolved, leading to progressive muscle replacement and tissue degeneration. Muscle-resident fibro-adipogenic progenitors are adaptable stromal cells with multilineage potential. They are required for muscle homeostasis, neuromuscular integrity, and tissue regeneration. Fibro-adipogenic progenitors actively regulate and shape the extracellular matrix and exert immunomodulatory functions via cross-talk with multiple other residents and non-resident muscle cells. Remarkably, cumulative evidence shows that a significant proportion of activated fibroblasts, adipocytes, and bone-cartilage cells, found after muscle trauma and disease, descend from these enigmatic interstitial progenitors. Despite the profound impact of muscle disease on human health, the fibrous, fatty, and ectopic bone tissues’ origins are poorly understood. Here, we review the current knowledge of fibro-adipogenic progenitor function on muscle homeostatic integrity, regeneration, repair, and aging. We also discuss how scar-forming pathologies and disorders lead to dysregulations in their behavior and plasticity and how these stromal cells can control the onset and severity of muscle loss in disease. We finally explore the rationale of improving muscle regeneration by understanding and modulating fibro-adipogenic progenitors’ fate and behavior.

scholarly journals Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuki Saito ◽  
Takako S. Chikenji
Keyword(s):  
Skeletal Muscle ◽  
Cellular Senescence ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Neuromuscular Disorders ◽  
Muscle Stem Cells ◽  
Related Disease ◽  
Tissue Degeneration ◽  
Cycle Arrest ◽  
Age Related

Skeletal muscle undergoes vigorous tissue remodeling after injury. However, aging, chronic inflammatory diseases, sarcopenia, and neuromuscular disorders cause muscle loss and degeneration, resulting in muscular dysfunction. Cellular senescence, a state of irreversible cell cycle arrest, acts during normal embryonic development and remodeling after tissue damage; when these processes are complete, the senescent cells are eliminated. However, the accumulation of senescent cells is a hallmark of aging tissues or pathological contexts and may lead to progressive tissue degeneration. The mechanisms responsible for the effects of senescent cells have not been fully elucidated. Here, we review current knowledge about the beneficial and detrimental effects of senescent cells in tissue repair, regeneration, aging, and age-related disease, especially in skeletal muscle. We also discuss how senescence of muscle stem cells and muscle-resident fibro-adipogenic progenitors affects muscle pathologies or regeneration, and consider the possibility that immunosenescence leads to muscle pathogenesis. Finally, we explore senotherapy, the therapeutic targeting of senescence to treat age-related disease, from the standpoint of improving muscle regeneration.

scholarly journals Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities

2021 ◽  
Vol 22 (11) ◽  
pp. 6167
Author(s):  
Carla Liaci ◽  
Mattia Camera ◽  
Giovanni Caslini ◽  
Simona Rando ◽  
Salvatore Contino ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Systems Biology ◽  
Rho Gtpases ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Hierarchical Arrangement ◽  
Worldwide Population ◽  
Id Genes ◽  
Effective Network ◽  
And Behavior

Intellectual disability (ID) is a pathological condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1–3% of the worldwide population, and no pharmacological therapies are currently available. More than 1000 genes have been found mutated in ID patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular level and moving toward higher levels of organization, i.e., cell compartment and functions, circuits, cognition, and behavior. Thus, cytoskeleton alterations that have an impact on cell processes such as neuronal migration, neuritogenesis, and synaptic plasticity rebound on the overall establishment of an effective network and consequently on the cognitive phenotype. Systems biology (SB) approaches are more focused on the overall interconnected network rather than on individual genes, thus encouraging the design of therapies that aim to correct common dysregulated biological processes. This review summarizes current knowledge about cytoskeleton control in neurons and its relevance for the ID pathogenesis, exploiting in silico modeling and translating the implications of those findings into biomedical research.

scholarly journals Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3191
Author(s):  
Katherine Po Sin Chung ◽  
Rainbow Wing Hei Leung ◽  
Terence Kin Wah Lee
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Special Focus ◽  
Intrinsic Regulation ◽  
Mechanistic Basis ◽  
Novel Therapeutic Strategies

Cancer stem cells (CSCs) within the tumor bulk play crucial roles in tumor initiation, recurrence and therapeutic resistance. In addition to intrinsic regulation, a growing body of evidence suggests that the phenotypes of CSCs are also regulated extrinsically by stromal cells in the tumor microenvironment (TME). Here, we discuss the current knowledge of the interplay between stromal cells and cancer cells with a special focus on how stromal cells drive the stemness of cancer cells and immune evasive mechanisms of CSCs. Knowledge gained from the interaction between CSCs and stromal cells will provide a mechanistic basis for the development of novel therapeutic strategies for the treatment of cancers.

scholarly journals Origins, potency, and heterogeneity of skeletal muscle fibro-adipogenic progenitors—time for new definitions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Osvaldo Contreras ◽  
Fabio M. V. Rossi ◽  
Marine Theret
Keyword(s):  
Extracellular Matrix ◽  
Muscle Development ◽  
Striated Muscle ◽  
Body Movement ◽  
Well Being ◽  
Lineage Tracing ◽  
Extracellular Matrix Components ◽  
Main Components ◽  
Muscle Homeostasis ◽  
Activated Fibroblasts

AbstractStriated muscle is a highly plastic and regenerative organ that regulates body movement, temperature, and metabolism—all the functions needed for an individual’s health and well-being. The muscle connective tissue’s main components are the extracellular matrix and its resident stromal cells, which continuously reshape it in embryonic development, homeostasis, and regeneration. Fibro-adipogenic progenitors are enigmatic and transformative muscle-resident interstitial cells with mesenchymal stem/stromal cell properties. They act as cellular sentinels and physiological hubs for adult muscle homeostasis and regeneration by shaping the microenvironment by secreting a complex cocktail of extracellular matrix components, diffusible cytokines, ligands, and immune-modulatory factors. Fibro-adipogenic progenitors are the lineage precursors of specialized cells, including activated fibroblasts, adipocytes, and osteogenic cells after injury. Here, we discuss current research gaps, potential druggable developments, and outstanding questions about fibro-adipogenic progenitor origins, potency, and heterogeneity. Finally, we took advantage of recent advances in single-cell technologies combined with lineage tracing to unify the diversity of stromal fibro-adipogenic progenitors. Thus, this compelling review provides new cellular and molecular insights in comprehending the origins, definitions, markers, fate, and plasticity of murine and human fibro-adipogenic progenitors in muscle development, homeostasis, regeneration, and repair.

LIMB-GIRDLE MUSCULAR DYSTROPHY: ITS LARGER SIGNIFICANCE

PEDIATRICS ◽  
1968 ◽  
Vol 41 (2) ◽  
pp. 382-384
Author(s):  
S. C.
Keyword(s):  
Peripheral Nerves ◽  
Neuromuscular Disorders ◽  
Serum Enzymes ◽  
Muscle Disease ◽  
Muscular Dystrophies ◽  
Muscular Weakness ◽  
Conduction Velocities ◽  
Clinical Awareness ◽  
Muscle Biopsies

The current literature reflects the interest of pediatricians, neurologists, and internists in the neuromuscular disorders of childhood.1-5 Clinical awareness and the availability and refinement of ancillary procedures, such as electromyography, measurement of nerve conduction velocities, determination of serum enzymes and muscle biopsies, have made it possible to differentiate many of these conditions and correctly localize the pathology of these lower motor neuron disorders to the anterior horn cells, the peripheral nerves, and/or the muscles.1 Primary muscle disease is the most frequent cause of progressive muscular weakness in children with neuromuscular disorders.2 The primary myopathies are either hereditary or acquired. The muscular dystrophies and the myotonic syndrome are representative of the genetic variety, while the acquired disorders are recognized clinically as polymyositis and dermatomyositis.

scholarly journals CXCL12 and Its Isoforms: Different Roles in Pancreatic Cancer?

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandra Righetti ◽  
Matteo Giulietti ◽  
Berina Šabanović ◽  
Giulia Occhipinti ◽  
Giovanni Principato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Invasion ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Tumor Development ◽  
Physiological Role ◽  
Mesenchymal Transition ◽  
Splicing Isoforms

CXCL12 is a chemokine that acts through CXCR4 and ACKR3 receptors and plays a physiological role in embryogenesis and haematopoiesis. It has an important role also in tumor development, since it is released by stromal cells of tumor microenvironment and alters the behavior of cancer cells. Many studies investigated the roles of CXCL12 in order to understand if it has an anti- or protumor role. In particular, it seems to promote tumor invasion, proliferation, angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in pancreatic cancer. Nevertheless, some evidence shows opposite functions; therefore research on CXCL12 is still ongoing. These discrepancies could be due to the presence of at least six CXCL12 splicing isoforms, each with different roles. Interestingly, three out of six variants have the highest levels of expression in the pancreas. Here, we report the current knowledge about the functions of this chemokine and then focus on pancreatic cancer. Moreover, we discuss the methods applied in recent studies in order to understand if they took into account the existence of the CXCL12 isoforms.

Cancer-associated fibroblasts (CAFs) in thyroid papillary carcinoma: molecular networks and interactions

2021 ◽  
pp. jclinpath-2020-207357
Author(s):  
Jeehoon Ham ◽  
Bin Wang ◽  
Joseph William Po ◽  
Amandeep Singh ◽  
Navin Niles ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Molecular Networks ◽  
Cancer Cell Growth ◽  
Molecular Events

In 1989, Stephen Paget proposed the ‘seed and soil’ theory of cancer metastasis. This theory has led to previous researchers focusing on the role of a tumour as a cancer seed and antiangiogenesis agents as cancer soil fumigant; for the latter to be effective, it is important for them to be able to distinguish cancer cells from stromal cells. However, antiangiogenesis agents have not produced dramatic survival benefits in vivo. This may be related to their inability to destroy the supporting stroma that promote cancer cell growth. Therefore, in order to effectively arrest cancer cell growth for therapeutic purposes, a paradigm shift is required in our fundamental approach to decipher the molecular events and networks in the stromal environment that cancer cells can thrive and proliferate. The pathogenesis of cancer is a multidimensional process of pathological molecular and cellular pathways, influencing different stromal properties and achieving a mutually negotiated crosstalk between cancer cells and stromal cells. This review summarises the clinical presentation of current knowledge of classical papillary thyroid carcinoma (PTC), emerging molecular diagnostics and future directions of classical PTC research.

scholarly journals Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

2019 ◽  
Vol 55 (5) ◽  
pp. 481-495 ◽  
Author(s):  
Toshio Watanabe ◽  
Yasuhiro Fujiwara ◽  
Francis K. L. Chan
Keyword(s):  
Small Bowel ◽  
Current Knowledge ◽  
Significant Proportion ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Drug Induced ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Small Bowel Endoscopy ◽  
Intestinal Ulcers

AbstractRecent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.

Advances in Microbiome Research for Animal Health

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Raquel S. Peixoto ◽  
Derek M. Harkins ◽  
Karen E. Nelson
Keyword(s):  
Current Knowledge ◽  
Animal Health ◽  
Biodiversity Loss ◽  
Emerging Diseases ◽  
Annual Review ◽  
Publication Date ◽  
Toxic Compounds ◽  
Symbiotic Interactions ◽  
Microbiome Research ◽  
And Behavior

Host-associated microbiomes contribute in many ways to the homeostasis of the metaorganism. The microbiome's contributions range from helping to provide nutrition and aiding growth, development, and behavior to protecting against pathogens and toxic compounds. Here we summarize the current knowledge of the diversity and importance of the microbiome to animals, using representative examples of wild and domesticated species. We demonstrate how the beneficial ecological roles of animal-associated microbiomes can be generally grouped into well-defined main categories and how microbe-based alternative treatments can be applied to mitigate problems for both economic and conservation purposes and to provide crucial knowledge about host–microbiota symbiotic interactions. We suggest a Customized Combination of Microbial-Based Therapies to promote animal health and contribute to the practice of sustainable husbandry. We also discuss the ecological connections and threats associated with animal biodiversity loss, microorganism extinction, and emerging diseases, such as the COVID-19 pandemic. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Role of Insulin-Like Growth Factor Receptor 2 across Muscle Homeostasis: Implications for Treating Muscular Dystrophy

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 441 ◽  
Author(s):  
Yvan Torrente ◽  
Pamela Bella ◽  
Luana Tripodi ◽  
Chiara Villa ◽  
Andrea Farini
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Muscle Disease ◽  
Insulin Like Growth Factor ◽  
Related Disease ◽  
Research Findings ◽  
Novel Approaches ◽  
And Migration ◽  
Muscle Homeostasis

The insulin-like growth factor 2 receptor (IGF2R) plays a major role in binding and regulating the circulating and tissue levels of the mitogenic peptide insulin-like growth factor 2 (IGF2). IGF2/IGF2R interaction influences cell growth, survival, and migration in normal tissue development, and the deregulation of IGF2R expression has been associated with growth-related disease and cancer. IGF2R overexpression has been implicated in heart and muscle disease progression. Recent research findings suggest novel approaches to target IGF2R action. This review highlights recent advances in the understanding of the IGF2R structure and pathways related to muscle homeostasis.

Sign in / Sign up

Export Citation Format

Share Document