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Immunity Mar 2016Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages... (Review)
Review
Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
Topics: Animals; Cell Communication; Cell Differentiation; Fibrosis; Humans; Macrophage Activation; Macrophages; Phenotype; Regeneration; Wound Healing
PubMed: 26982353
DOI: 10.1016/j.immuni.2016.02.015 -
Physiological Reviews Jul 2022Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological... (Review)
Review
Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.
Topics: Cell Lineage; Humans; Oral Health; Regeneration; Salivary Glands; Signal Transduction
PubMed: 35343828
DOI: 10.1152/physrev.00015.2021 -
Development (Cambridge, England) Sep 2019Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies... (Review)
Review
Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies across tissues and between species. Determining the natural mechanisms behind regeneration in model organisms that regenerate well can help us develop strategies for tissue recovery in species with poor regenerative capacity (such as humans). The zebrafish () is one of the most accessible vertebrate models to study regeneration. In this Primer, we highlight the tools available to study regeneration in the zebrafish, provide an overview of the mechanisms underlying regeneration in this system and discuss future perspectives for the field.
Topics: Animals; Drug Evaluation, Preclinical; Genetic Techniques; Humans; Models, Animal; Organogenesis; Regeneration; Zebrafish
PubMed: 31540899
DOI: 10.1242/dev.167692 -
The Journal of Investigative Dermatology Oct 2022Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new... (Review)
Review
Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new hair follicles regenerate in the center of large full-thickness wounds of mice in a process called wound-induced hair neogenesis (WIHN). WIHN is followed by neogenesis of dermal adipose tissue. Both neogenic events reactivate embryonic-like cellular and molecular programs. The WIHN model provides a platform for studying mammalian regeneration, and findings from this model could instruct future regenerative medicine interventions for treating wounds and alopecia. Since Ito et al. rediscovered WIHN 15 years ago, numerous investigators have worked on the WIHN model using varying wounding protocols and model interpretations. Because a variety of factors, including environmental variables and choice of mouse strains, can affect the outcomes of a WIHN study, the purpose of this article is to provide an overview of the experimental variables that impact WIHN so that experiments between laboratories can be compared in a meaningful manner.
Topics: Animals; Hair; Hair Follicle; Mammals; Mice; Mice, Inbred C57BL; Regeneration; Skin; Wound Healing
PubMed: 36153062
DOI: 10.1016/j.jid.2022.07.013 -
Developmental Cell Feb 2016Adult humans fail to regenerate their hearts following injury, and this failure to regenerate myocardium is a leading cause of heart failure and death worldwide.... (Review)
Review
Adult humans fail to regenerate their hearts following injury, and this failure to regenerate myocardium is a leading cause of heart failure and death worldwide. Although all adult mammals appear to lack significant cardiac regeneration potential, some vertebrates can regenerate myocardium throughout life. In addition, new studies indicate that mammals have cardiac regeneration potential during development and very soon after birth. The mechanisms of heart regeneration among model organisms, including neonatal mice, appear remarkably similar. Orchestrated waves of inflammation, matrix deposition and remodeling, and cardiomyocyte proliferation are commonly seen in heart regeneration models. Understanding why adult mammals develop extensive scarring instead of regeneration is a crucial goal for regenerative biology.
Topics: Animals; Cell Proliferation; Heart; Humans; Mammals; Myocardium; Myocytes, Cardiac; Regeneration
PubMed: 26906733
DOI: 10.1016/j.devcel.2016.01.018 -
Physiological Reviews Oct 2015After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of... (Review)
Review
After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.
Topics: Animals; Cell Differentiation; Heart; Heart Diseases; Humans; Myocytes, Cardiac; Regeneration; Stem Cells
PubMed: 26269526
DOI: 10.1152/physrev.00021.2014 -
Neuron Aug 2022Injured neurons in the adult mammalian central nervous system often die and seldom regenerate axons. To uncover transcriptional pathways that could ameliorate these...
Injured neurons in the adult mammalian central nervous system often die and seldom regenerate axons. To uncover transcriptional pathways that could ameliorate these disappointing responses, we analyzed three interventions that increase survival and regeneration of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC) injury, albeit not to a clinically useful extent. We assessed gene expression in each of 46 RGC types by single-cell transcriptomics following ONC and treatment. We also compared RGCs that regenerated with those that survived but did not regenerate. Each intervention enhanced survival of most RGC types, but type-independent axon regeneration required manipulation of multiple pathways. Distinct computational methods converged on separate sets of genes selectively expressed by RGCs likely to be dying, surviving, or regenerating. Overexpression of genes associated with the regeneration program enhanced both survival and axon regeneration in vivo, indicating that mechanistic analysis can be used to identify novel therapeutic strategies.
Topics: Animals; Axons; Cell Survival; Mammals; Mice; Nerve Regeneration; Optic Nerve Injuries; Retinal Ganglion Cells
PubMed: 35767994
DOI: 10.1016/j.neuron.2022.06.002 -
Journal of Endodontics Jan 2023The conventional treatment for irreversibly inflamed or necrotic teeth is root canal treatment or apexification. Regenerative endodontics aims to regenerate the damaged... (Review)
Review
INTRODUCTION
The conventional treatment for irreversibly inflamed or necrotic teeth is root canal treatment or apexification. Regenerative endodontics aims to regenerate the damaged "pulp-like" tissue, which can preserve the teeth' vitality and sensitivity while avoiding necrosis. The main clinical benefit is root maturation. The "pulp-like" tissue does not refer to regenerated pulp tissue with an odontoblastic layer or the formation of pulp-dentin complexes. The cell homing technique is built on endogenous stem cells and their capacity to regenerate tissue. Cell homing refers to endogenous cells' migration or infiltration into the cite when stimulated by physiochemical or biological stimuli or by passive flow with a blood clot from the apical tissue. Its Regenerative Endodontic Procedures success criteria are defined by the American Association of Endodontists. The purpose of this article is to provide an overview of vital pulp tissue and various strategies to promote regeneration of damaged pulp tissue. The cell homing technique will be reviewed through clinical trials.
METHODS
We performed a comprehensive literature review on a total of nine clinical trials of regenerative endodontics using the cell-homing technique based on three databases and duplicate manuscripts were removed.
RESULTS
Regenerative endodontics using the cell-homing technique shows promising results that can be translated into clinical practice. However, a favorable result was observed in immature teeth, and the results are contradictory in mature teeth.
CONCLUSION
Regeneration therapy is an attractive new alternative to conventional endodontic treatments. Preservation of vitality and continuation of root development in damaged teeth would be a clear advantage.
Topics: Humans; Regenerative Endodontics; Dental Pulp Necrosis; Tooth Apex; Apexification; Dental Pulp; Root Canal Therapy; Regeneration; Endodontics
PubMed: 36270575
DOI: 10.1016/j.joen.2022.09.008 -
International Journal of Molecular... Oct 2020Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor... (Review)
Review
Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor deficits. Currently, there is no effective therapeutic method to restore neurological function because the adult CNS has limited capacity to regenerate after injury. Many efforts have been made to understand the molecular and cellular mechanisms underlying CNS regeneration and to establish novel therapeutic methods based on these mechanisms, with a variety of strategies including cell transplantation, modulation of cell intrinsic molecular mechanisms, and therapeutic targeting of the pathological nature of the extracellular environment in CNS injury. In this review, we will focus on the mechanisms that regulate CNS regeneration, highlighting the history, recent efforts, and questions left unanswered in this field.
Topics: Animals; Axons; Central Nervous System; Humans; Myelin Sheath; Nerve Regeneration; Remyelination
PubMed: 33143194
DOI: 10.3390/ijms21218116 -
Proceedings of the National Academy of... Mar 2020Aging manifests with architectural alteration and functional decline of multiple organs throughout an organism. In mammals, aged skin is accompanied by a marked...
Aging manifests with architectural alteration and functional decline of multiple organs throughout an organism. In mammals, aged skin is accompanied by a marked reduction in hair cycling and appearance of bald patches, leading researchers to propose that hair follicle stem cells (HFSCs) are either lost, differentiate, or change to an epidermal fate during aging. Here, we employed single-cell RNA-sequencing to interrogate aging-related changes in the HFSCs. Surprisingly, although numbers declined, aging HFSCs were present, maintained their identity, and showed no overt signs of shifting to an epidermal fate. However, they did exhibit prevalent transcriptional changes particularly in extracellular matrix genes, and this was accompanied by profound structural perturbations in the aging SC niche. Moreover, marked age-related changes occurred in many nonepithelial cell types, including resident immune cells, sensory neurons, and arrector pili muscles. Each of these SC niche components has been shown to influence HF regeneration. When we performed skin injuries that are known to mobilize young HFSCs to exit their niche and regenerate HFs, we discovered that aged skin is defective at doing so. Interestingly, however, in transplantation assays in vivo, aged HFSCs regenerated HFs when supported with young dermis, while young HFSCs failed to regenerate HFs when combined with aged dermis. Together, our findings highlight the importance of SC:niche interactions and favor a model where youthfulness of the niche microenvironment plays a dominant role in dictating the properties of its SCs and tissue health and fitness.
Topics: Animals; Dermis; Epidermal Cells; Epidermis; Hair Follicle; Mice; Mice, Inbred C57BL; Muscles; Re-Epithelialization; Regeneration; Sensory Receptor Cells; Skin Aging; Stem Cell Niche; Stem Cell Transplantation; Stem Cells; Transcriptome; Wound Healing
PubMed: 32094197
DOI: 10.1073/pnas.1901720117