BACKGROUND: Embryos are regeneration and wound healing masters. They rapidly close wounds and scarlessly remodel and regenerate injured tissue. Regeneration has been extensively studied in many animal models using new tools such as single-cell analysis. However, until now, they have been based primarily on experiments assessing from 1 day post injury. RESULTS: In this paper, we reveal that critical steps initiating regeneration occur within hours after injury. We discovered the regeneration initiating cells (RICs) using single-cell and spatial transcriptomics of the regenerating Xenopus laevis tail. RICs are formed transiently from the basal epidermal cells, and their expression signature suggests they are important for modifying the surrounding extracellular matrix thus regulating development. The absence or deregulation of RICs leads to excessive extracellular matrix deposition and defective regeneration. CONCLUSION: RICs represent a newly discovered transient cell state involved in the initiation of the regeneration process.

• Klíčová slova
• Xenopus laevis, RICs, ROCs, Regeneration,
• MeSH
• analýza jednotlivých buněk MeSH
• extracelulární matrix metabolismus   MeSH
• hojení ran MeSH
• ocas * MeSH
• regenerace * MeSH
• transkriptom MeSH
• Xenopus laevis * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Non-malignant and malignant obstruction of the tracheal airway causes significant morbidity and mortality. With increased use of artificial airways, benign and iatrogenic complications are increasing. A tracheal stenosis that is less than 5 cm in length can be resected with end-to-end anastomosis. Longer tracheal lesions can be treated in a palliative way by placement of a stent to secure airway lumen patency. The management of tracheal defects is an evolving field. Tracheal transplantation and tracheal regeneration may provide major treatment advances to cases with long-segment tracheal involvement. This review examines the current possibilities and future prospects in the area of tracheal transplantation and regeneration.

• Klíčová slova
• Trachea, allotransplantation, immunosuppression regeneration., revascularization,
• MeSH
• homologní transplantace MeSH
• lidé MeSH
• regenerace MeSH
• trachea fyziologie   transplantace   MeSH
• transplantace orgánů metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However, extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of α9 integrin and its activator kindlin-1 (α9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of adult male rat DRG sensory neurons transduced with α9k1, and controls, with and without axotomy of the central branch. Expression of α9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling α9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration. In addition to the program upregulated by α9k1 expression, regeneration in the spinal cord led to expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum (ER), trafficking, and signaling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPSC-derived sensory neurons, validating their causal contributions to sensory regeneration. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, and Yy1. Signaling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with an additional distinctive program that differs from that involved in PNS regeneration.SIGNIFICANCE STATEMENT Restoration of neurologic function after spinal cord injury has yet to be achieved in human patients. To accomplish this, severed nerve fibers must be made to regenerate. Reconstruction of nerve pathways has not been possible, but recently, a method for stimulating long-distance axon regeneration of sensory fibers in rodents has been developed. This research uses profiling of messenger RNAs in the regenerating sensory neurons to discover which mechanisms are activated. This study shows that the regenerating neurons initiate a novel CNS regeneration program which includes molecular transport, autophagy, ubiquitination, and modulation of the endoplasmic reticulum (ER). The study identifies mechanisms that neurons need to activate to regenerate their nerve fibers.

• Klíčová slova
• autophagy, axon regeneration, integrin, sensory, signaling, spinal cord,
• MeSH
• axony * fyziologie   MeSH
• integriny metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mícha metabolismus   MeSH
• nervové receptory fyziologie   MeSH
• poranění míchy * terapie   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• regenerace nervu fyziologie   MeSH
• spinální ganglia metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• integriny MeSH

Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling. Integrin biology is more complex in the central nervous system. Integrins receptors are transported into growing axons during development, but selective polarised transport of integrins limits the regenerative response in adult neurons. Manipulation of integrins and related molecules to control their activation state and localisation within axons is a promising route towards stimulating effective regeneration in the central nervous system.

• Klíčová slova
• axon regeneration, integrin, kindlin, receptor activation state, selective polarised transport, traumatic injury of the nervous system,
• MeSH
• axony fyziologie   MeSH
• integriny genetika   metabolismus   MeSH
• rány a poranění * MeSH
• regenerace nervu fyziologie   MeSH
• regulace genové exprese fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• integriny MeSH

This chapter provides a review of immune reactions involved in classic as well as alternative methods of peripheral nerve regeneration, and mainly with a view to understanding their beneficial effects. Axonal degeneration distal to nerve damage triggers a cascade of inflammatory events alongside injured nerve fibers known as Wallerian degeneration (WD). The early inflammatory reactions of WD comprise the complement system, arachidonic acid metabolites, and inflammatory mediators that are related to myelin fragmentation and activation of Schwann cells. Fine-tuned upregulation of the cytokine/chemokine network by Schwann cells activates resident and hematogenous macrophages to complete the clearance of axonal and myelin debris and stimulate regrowth of axonal sprouts. In addition to local effects, immune reactions of neuronal bodies and glial cells are also implicated in the survival and conditioning of neurons to regenerate severed nerves. Understanding of the cellular and molecular interactions between the immune system and peripheral nerve injury opens new possibilities for targeting inflammatory mediators to improve functional reinnervation.

• Klíčová slova
• Axonal regeneration, Cytokines, Immune cells, Inflammatory mediators, Neuroinflammation, Wallerian degeneration,
• MeSH
• cytokiny imunologie   metabolismus   MeSH
• lidé MeSH
• periferní nervy imunologie   metabolismus   MeSH
• poranění periferního nervu imunologie   metabolismus   MeSH
• regenerace nervu fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• Wallerova degenerace imunologie   metabolismus   MeSH
• zánět imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.

• Klíčová slova
• axon growth, axon regeneration, inter-organelle membrane contact sites, organelles,
• MeSH
• lidé MeSH
• organely metabolismus   patologie   MeSH
• poranění míchy * metabolismus   patologie   terapie   MeSH
• regenerace nervu * MeSH
• růstové kužele metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Spinal cord repair research appeared to have run out of new ideas in the 1970s. In a 1981 paper, the Aguayo Laboratory revisited an experiment by Tello and Cajal that suggested that central nervous system (CNS) axons could regenerate into peripheral nerve grafts. Using modern axon tracing methods, David and Aguayo showed that axons from neurons in the spinal cord could regenerate for long distances within peripheral nervous system (PNS) grafts, but not back into the CNS. This proved that damaged CNS tissue is inhibitory to axon regeneration while PNS tissue is permissive. The experiment sparked a research revival, leading to the identification of many inhibitory molecules that block axon growth in the mature CNS.

• Klíčová slova
• axon regeneration, spinal cord injury,
• MeSH
• axony MeSH
• centrální nervový systém MeSH
• krysa rodu Rattus MeSH
• periferní nervový systém MeSH
• poranění míchy * MeSH
• poranění nervového systému * MeSH
• regenerace nervu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

Regeneration capacity is reduced as CNS axons mature. Using laser-mediated axotomy, proteomics and puromycin-based tagging of newly-synthesized proteins in a human embryonic stem cell-derived neuron culture system that allows isolation of axons from cell bodies, we show here that efficient regeneration in younger axons (d45 in culture) is associated with local axonal protein synthesis (local translation). Enhanced regeneration, promoted by co-culture with human glial precursor cells, is associated with increased axonal synthesis of proteins, including those constituting the translation machinery itself. Reduced regeneration, as occurs with the maturation of these axons by d65 in culture, correlates with reduced levels of axonal proteins involved in translation and an inability to respond by increased translation of regeneration promoting axonal mRNAs released from stress granules. Together, our results provide evidence that, as in development and in the PNS, local translation contributes to CNS axon regeneration.

• Klíčová slova
• Axon regeneration, Axotomy, Human stem cells, In vitro live imaging, Local translation, Proteomics,
• MeSH
• axony fyziologie   MeSH
• embryonální kmenové buňky fyziologie   MeSH
• kokultivační techniky MeSH
• lidé MeSH
• proteosyntéza fyziologie   MeSH
• regenerace nervu fyziologie   MeSH
• stárnutí buněk fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Smoking modifies morphological and physiological parameters of the lungs. Due to the irritation of airways, the natural self-cleaning ability of the lungs is impaired. The mucus accumulates in the airways and various infections develop, leading to chronic bronchitis. After the cessation of smoking, the lungs of the smoker start to heal and regenerate. Cilia in the lungs start to grow again and cleanse the lungs, thus reducing the risk of infection. The regeneration of the lungs takes a long time and depends on the degree of lung damage due to smoking. The aim of this study was to reconstruct the evolution of this regeneration process in chronic smokers by using the biological effects of radon and its decay products. Thus, radon in this study served as a tracer of changes induced by smoking.

• MeSH
• biologické modely * MeSH
• kouření škodlivé účinky   MeSH
• lidé MeSH
• obstrukční plicní nemoci diagnóza   etiologie   MeSH
• plíce cytologie   MeSH
• počítačová simulace MeSH
• radon analýza   MeSH
• regenerace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• radon MeSH

Mammalian neurons lose the ability to regenerate their central nervous system axons as they mature during embryonic or early postnatal development. Neuronal maturation requires a transformation from a situation in which neuronal components grow and assemble to one in which these components are fixed and involved in the machinery for effective information transmission and computation. To regenerate after injury, neurons need to overcome this fixed state to reactivate their growth programme. A variety of intracellular processes involved in initiating or sustaining neuronal maturation, including the regulation of gene expression, cytoskeletal restructuring and shifts in intracellular trafficking, have been shown to prevent axon regeneration. Understanding these processes will contribute to the identification of targets to promote repair after injury or disease.

• MeSH
• axony * fyziologie   MeSH
• lidé MeSH
• neurogeneze * fyziologie   MeSH
• neurony fyziologie   MeSH
• regenerace nervu * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH