-
Cells Jan 2021The ability to regenerate amputated or injured tissues and organs is a fascinating property shared by several invertebrates and, interestingly, some vertebrates. The... (Review)
Review
The ability to regenerate amputated or injured tissues and organs is a fascinating property shared by several invertebrates and, interestingly, some vertebrates. The mechanism of evolutionary loss of regeneration in mammals is not understood, yet from the biomedical and clinical point of view, it would be very beneficial to be able, at least partially, to restore that capability. The current availability of new experimental tools, facilitating the comparative study of models with high regenerative ability, provides a powerful instrument to unveil what is needed for a successful regeneration. The present review provides an updated overview of multiple aspects of appendage regeneration in three vertebrates: lizard, salamander, and zebrafish. The deep investigation of this process points to common mechanisms, including the relevance of Wnt/β-catenin and FGF signaling for the restoration of a functional appendage. We discuss the formation and cellular origin of the blastema and the identification of epigenetic and cellular changes and molecular pathways shared by vertebrates capable of regeneration. Understanding the similarities, being aware of the differences of the processes, during lizard, salamander, and zebrafish regeneration can provide a useful guide for supporting effective regenerative strategies in mammals.
Topics: Animals; Body Patterning; Epigenesis, Genetic; Extremities; Phylogeny; Regeneration; Vertebrates
PubMed: 33513779
DOI: 10.3390/cells10020242 -
Cells Sep 2020The capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that...
The capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that partially recapitulates the embryonic developmental program and involves the activation of the muscle compartment of stem cells, namely satellite cells, as well as other precursor cells, whose activity is strictly dependent on environmental signals. However, muscle regeneration is severely compromised in several pathological conditions due to either the progressive loss of stem cell populations or to missing signals that limit the damaged tissues from efficiently activating a regenerative program. It is, therefore, plausible that the loss of control over these cells' fate might lead to pathological cell differentiation, limiting the ability of a pathological muscle to sustain an efficient regenerative process. This Special Issue aims to bring together a collection of original research and review articles addressing the intriguing field of the cellular and molecular players involved in muscle homeostasis and regeneration and to suggest potential therapeutic approaches for degenerating muscle disease.
Topics: Cell Differentiation; Homeostasis; Humans; Muscle, Skeletal; Regeneration
PubMed: 32899793
DOI: 10.3390/cells9092033 -
Developmental Dynamics : An Official... Jun 2022Axolotls represent a popular model to study how nature solved the problem of regenerating lost appendages in tetrapods. Our work over many years focused on trying to... (Review)
Review
Axolotls represent a popular model to study how nature solved the problem of regenerating lost appendages in tetrapods. Our work over many years focused on trying to understand how these animals can achieve such a feat and not end up with a scarred up stump. The Tgf-β superfamily represents an interesting family to target since they are involved in wound healing in adults and pattern formation during development. This family is large and comprises Tgf-β, Bmps, activins and GDFs. In this review, we present work from us and others on Tgf-β & Bmps and highlight interesting observations between these two sub-families. Tgf-β is important for the preparation phase of regeneration and Bmps for the redevelopment phase and they do not overlap with one another. We present novel data showing that the Tgf-β non-canonical pathway is also not active during redevelopment. Finally, we propose a molecular model to explain how Tgf-β and Bmps maintain distinct windows of expression during regeneration in axolotls.
Topics: Ambystoma mexicanum; Animals; Bone Morphogenetic Proteins; Regeneration; Transforming Growth Factor beta; Wound Healing
PubMed: 34096672
DOI: 10.1002/dvdy.379 -
Journal of Cachexia, Sarcopenia and... Jun 2022Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient... (Review)
Review
Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient breakdown, and as a regulator of cellular architecture. Its biological functions include metabolic stress adaptation, stem cell differentiation, immunomodulation and diseases regulation, and so on. Current researches have proved that autophagy dysfunction may contribute to the pathogenesis of some myopathies through impairment of myofibres regeneration. Studies of autophagy inhibition also indicate the importance of autophagy in muscle regeneration, while activation of autophagy can restore muscle function in some myopathies. In this review, we aim to report the mechanisms of action of autophagy on muscle regeneration to provide relevant references for the treatment of regenerating defective myopathies by regulating autophagy. Results have shown that one key mechanism of autophagy regulating the muscle regeneration is to affect the differentiation fate of muscle stem cells (MuSCs), including quiescence maintenance, activation and differentiation. The roles of autophagy (organelle/protein degradation, energy facilitation, and/or other) vary at different myogenic stages of the repair process. When the muscle is in homeostasis, basal autophagy can maintain the quiescence state and stemness of MuSCs by renewing organelle and protein. After injury, the increased autophagy flux contributes to meet biological energy demand of MuSCs during activation and proliferation. By mitochondrial remodelling, autophagy during differentiation can promote the metabolic transformation and balance mitochondrial-mediated apoptosis signals in myoblasts. Autophagy in mature myofibres is also essential for the degradation of necrotic myofibres, and may affect the dynamics of MuSCs by affecting the secretion spectrum of myofibres or the recruitment of supporting cells. Except for myogenic cells, autophagy also plays an important role in regulating the function of non-myogenic cells in the muscle microenvironment, which is also essential for successful muscle recovery. Autophagy can regulate the immune microenvironment during muscle regeneration through the recruitment and polarization of macrophages, while autophagy in endothelial cells can regulate muscle regeneration in an angiogenic or angiogenesis-independent manner. Drug or nutrition targeted autophagy has been preliminarily proved to restore muscle function in myopathies by promoting muscle regeneration, and further understanding the role and mechanism of autophagy in various cell types during muscle regeneration will enable more effective combinatorial therapeutic strategies.
Topics: Autophagy; Endothelial Cells; Humans; Muscle, Skeletal; Muscular Diseases; Regeneration
PubMed: 35434959
DOI: 10.1002/jcsm.13000 -
Experimental Cell Research Dec 2021Adult skeletal muscle regenerates completely after a damage, thanks to the satellite cells, or muscle stem cells (MuSCs), that implement the adult myogenic program. This... (Review)
Review
Adult skeletal muscle regenerates completely after a damage, thanks to the satellite cells, or muscle stem cells (MuSCs), that implement the adult myogenic program. This program is sustained by both robust intrinsic mechanisms and extrinsic cues coming from the close neighborhood of MuSCs during muscle regeneration. Among the various cell types present in the regenerating muscle, immune cells, and particularly macrophages, exert numerous functions and provide sequential transient niches to support the myogenic program. The adequate orchestration of the delivery of these cues ensures efficient muscle regeneration and full functional recovery. The situation is very different in muscular dystrophies where asynchronous and permanent microinjuries occur, triggering contradictory regenerating cues at the same time in a specific area, that lead to chronic inflammation and fibrogenesis. Here we review the beneficial effects that leukocytes, and particularly macrophages, exert on their neighboring cells during skeletal muscle regeneration after an acute injury. Then, the more complicated (and less beneficial) roles of leukocytes during muscular dystrophies are presented. Finally, we discuss how the inflammatory compartment may be a target to improve muscle regeneration in both acute muscle injury and muscle diseases.
Topics: Animals; Cell Differentiation; Humans; Inflammation; Macrophages; Muscle Development; Muscle, Skeletal; Regeneration; Wound Healing
PubMed: 34736921
DOI: 10.1016/j.yexcr.2021.112905 -
Journal of Experimental Zoology. Part... Mar 2021Among tetrapods, only salamanders can regenerate their limbs and tails throughout life. This amazing regenerative ability has attracted the attention of scientists for... (Review)
Review
Among tetrapods, only salamanders can regenerate their limbs and tails throughout life. This amazing regenerative ability has attracted the attention of scientists for hundreds of years. Now that large, salamander genomes are beginning to be sequenced for the first time, omics tools and approaches can be used to integrate new perspectives into the study of tissue regeneration. Here we argue the need to move beyond the primary salamander models to investigate regeneration in other species. Salamanders at first glance come across as a phylogenetically conservative group that has not diverged greatly from their ancestors. While salamanders do present ancestral characteristics of basal tetrapods, including the ability to regenerate limbs, data from fossils and data from studies that have tested for species differences suggest there may be considerable variation in how salamanders develop and regenerate their limbs. We review the case for expanded studies of salamander tissue regeneration and identify questions and approaches that are most likely to reveal commonalities and differences in regeneration among species. We also address challenges that confront such an initiative, some of which are regulatory and not scientific. The time is right to gain evolutionary perspective about mechanisms of tissue regeneration from comparative studies of salamander species.
Topics: Animals; Extremities; Regeneration; Species Specificity; Urodela
PubMed: 31584252
DOI: 10.1002/jez.b.22902 -
Annual Review of Biomedical Engineering Jun 2022Chronic skin wounds are commonly found in older individuals who have impaired circulation due to diabetes or are immobilized due to physical disability. Chronic wounds... (Review)
Review
Chronic skin wounds are commonly found in older individuals who have impaired circulation due to diabetes or are immobilized due to physical disability. Chronic wounds pose a severe burden to the health-care system and are likely to become increasingly prevalent in aging populations. Various treatment approaches exist to help the healing process, although the healed tissue does not generally recapitulate intact skin but rather forms a scar that has inferior mechanical properties and that lacks appendages such as hair or sweat glands. This article describes new experimental avenues for attempting to improve the regenerative response of skin using biophysical techniques as well as biochemical methods, in some cases by trying to harness the potential of stem cells, either endogenous to the host or provided exogenously, to regenerate the skin. These approaches primarily address the local wound environment and should likely be combined with other modalities to address regional and systemic disease, as well as social determinants of health.
Topics: Aged; Humans; Regeneration; Skin; Stem Cells; Wound Healing
PubMed: 35226819
DOI: 10.1146/annurev-bioeng-010220-113008 -
Developmental Dynamics : An Official... Jun 2021Salamanders stand out among vertebrate animals in two key characteristics: their ability to regenerate body parts, and their large and variable genome sizes. (Review)
Review
BACKGROUND
Salamanders stand out among vertebrate animals in two key characteristics: their ability to regenerate body parts, and their large and variable genome sizes.
RESULTS
Here we show how to unite seemingly disparate facets of salamander biology, regeneration ability, and genome size variation, into one synthetic view. Large and variable genome sizes may be the key to understanding the prodigious ability of most salamanders to regenerate damaged or lost body parts. We report a correlate of genome size variation that has been previously neglected: the impacts of genome size on the structure and function of the genes themselves. Salamanders are, in essence, paradoxically much younger, especially at the cellular level than their chronological age would suggest.
CONCLUSIONS
Because of the large size and range of variation in genome size in salamanders, we hypothesize that this relationship uncouples a dynamic interaction between growth and differentiation in processes of morphogenesis, pattern formation, and regeneration in ways that are unique among vertebrates.
Topics: Animals; Genome; Genome Size; Regeneration; Urodela
PubMed: 33320991
DOI: 10.1002/dvdy.279 -
Odontology Apr 2021A loss of organs or the destruction of tissue leaves wounds to which organisms and living things react differently. Their response depends on the extent of damage, the... (Review)
Review
A loss of organs or the destruction of tissue leaves wounds to which organisms and living things react differently. Their response depends on the extent of damage, the functional impairment and the biological potential of the organism. Some can completely regenerate lost body parts or tissues, whereas others react by forming scars in the sense of a tissue repair. Overall, the regenerative capacities of the human body are limited and only a few tissues are fully restored when injured. Dental tissues may suffer severe damage due to various influences such as caries or trauma; however, dental care aims at preserving unharmed structures and, thus, the functionality of the teeth. The dentin-pulp complex, a vital compound tissue that is enclosed by enamel, holds many important functions and is particularly worth protecting. It reacts physiologically to deleterious impacts with an interplay of regenerative and reparative processes to ensure its functionality and facilitate healing. While there were initially no biological treatment options available for the irreversible destruction of dentin or pulp, many promising approaches for endodontic regeneration based on the principles of tissue engineering have been developed in recent years. This review describes the regenerative and reparative processes of the dentin-pulp complex as well as the morphological criteria of possible healing results. Furthermore, it summarizes the current knowledge on tissue engineering of dentin and pulp, and potential future developments in this thriving field.
Topics: Dental Pulp; Dentin; Humans; Regeneration; Tissue Engineering; Wound Healing
PubMed: 33263826
DOI: 10.1007/s10266-020-00573-1 -
Genome Research Aug 2023In contrast to other mammals, the spiny mouse () regenerates skin and ear tissue, which includes hair follicles, glands, and cartilage, in a scar-free manner. Ear punch...
In contrast to other mammals, the spiny mouse () regenerates skin and ear tissue, which includes hair follicles, glands, and cartilage, in a scar-free manner. Ear punch regeneration is asymmetric with only the proximal wound side participating in regeneration. Here, we show that cues originating from the proximal side are required for normal regeneration and use spatially resolved transcriptomics (tomo-seq) to understand the molecular and cellular events underlying this process. Analyzing gene expression across the ear and comparing expression modules between proximal and distal wound sides, we identify asymmetric gene expression patterns and pinpoint regenerative processes in space and time. Moreover, using a comparative approach with nonregenerative rodents (, ), we strengthen a hypothesis in which particularities in the injury-induced immune response may be one of the crucial determinants for why spiny mice regenerate whereas their relatives do not. Our data are available in SpinyMine, an easy-to-use and expandable web-based tool for exploring regeneration-associated gene expression.
Topics: Animals; Wound Healing; Murinae; Transcriptome; Regeneration; Skin; Mammals
PubMed: 37726147
DOI: 10.1101/gr.277538.122