scholarly journals Pain sensing neurons promote tissue regeneration in adult mice

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lise Rabiller ◽  
Elodie Labit ◽  
Christophe Guissard ◽  
Silveric Gilardi ◽  
Bruno P. Guiard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tissue Regeneration ◽  
Tissue Repair ◽  
Animal Species ◽  
Loss Of Function ◽  
Nociceptive Neurons ◽  
Regulatory Processes ◽  
Adult Mice ◽  
Calcitonin Gene ◽  
Lower Vertebrates

AbstractTissue repair after injury in adult mammals, usually results in scarring and loss of function in contrast to lower vertebrates such as the newt and zebrafish that regenerate. Understanding the regulatory processes that guide the outcome of tissue repair is therefore a concerning challenge for regenerative medicine. In multiple regenerative animal species, the nerve dependence of regeneration is well established, but the nature of the innervation required for tissue regeneration remains largely undefined. Using our model of induced adipose tissue regeneration in adult mice, we demonstrate here that nociceptive nerves promote regeneration and their removal impairs tissue regeneration. We also show that blocking the receptor for the nociceptive neuropeptide calcitonin gene-related peptide (CGRP) inhibits regeneration, whereas CGRP administration induces regeneration. These findings reveal that peptidergic nociceptive neurons are required for adult mice tissue regeneration.

scholarly journals Driving regeneration, instead of healing, in adult mammals: the decisive role of resident macrophages through efferocytosis

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lise Rabiller ◽  
Virginie Robert ◽  
Adèle Arlat ◽  
Elodie Labit ◽  
Marielle Ousset ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Tissue Repair ◽  
Decisive Role ◽  
Specific Cell ◽  
Loss Of Function ◽  
Adult Mice ◽  
Ability To Regenerate ◽  
Cellular Pathways ◽  
Scar Healing

AbstractTissue repair after lesion usually leads to scar healing and thus loss of function in adult mammals. In contrast, other adult vertebrates such as amphibians have the ability to regenerate and restore tissue homeostasis after lesion. Understanding the control of the repair outcome is thus a concerning challenge for regenerative medicine. We recently developed a model of induced tissue regeneration in adult mice allowing the comparison of the early steps of regenerative and scar healing processes. By using studies of gain and loss of function, specific cell depletion approaches, and hematopoietic chimeras we demonstrate here that tissue regeneration in adult mammals depends on an early and transient peak of granulocyte producing reactive oxygen species and an efficient efferocytosis specifically by tissue-resident macrophages. These findings highlight key and early cellular pathways able to drive tissue repair towards regeneration in adult mammals.

scholarly journals Inhibition of granulocyte ROS production by opioids prevents regeneration

2017 ◽  
Author(s):  
Elodie Labit ◽  
Lise Rabiller ◽  
Christophe Guissard ◽  
Mireille Andre ◽  
Christine Rampon ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Gold Standard ◽  
Tissue Repair ◽  
Opioid Antagonist ◽  
Ros Production ◽  
Oxygen Species ◽  
Loss Of Function ◽  
Adult Zebrafish ◽  
Mu Receptors

SUMMARYInhibition of regeneration and induction of healing are classic outcomes of tissue repair in adult mammals. Here, by using gain and loss of function experiments, we demonstrate that both endogenous and exogenous opioids prevent tissue regeneration in adults, by inhibiting the early reactive oxygen species (ROS) production occurring after lesion and required for regeneration. These effects can be overcome and regeneration induced by the use of an opioid antagonist. These results, obtained in both gold-standard adult zebrafish and a newly-developed model of regeneration in adult mammals, demonstrate that this mechanism can be considered as a general paradigm in vertebrates. In addition, we show that opioids act via signaling through peripheral mu-receptors expressed on granulocytes. This work clearly demonstrates the deleterious role of opioids on tissue regeneration through the control of ROS production in vertebrates and thus questions about opioid-based analgesia in perioperative care.

scholarly journals Microvesicles from Human Immortalized Cell Lines of Endothelial Progenitor Cells and Mesenchymal Stem/Stromal Cells of Adipose Tissue Origin as Carriers of Bioactive Factors Facilitating Angiogenesis

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Agnieszka Krawczenko ◽  
Aleksandra Bielawska-Pohl ◽  
Maria Paprocka ◽  
Honorata Kraskiewicz ◽  
Agnieszka Szyposzynska ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Immortalized Cell ◽  
Dose Dependent ◽  
Tissue Origin

Endothelial progenitor cells (EPCs) and mesenchymal stem/stromal cells (MSCs) are associated with maintaining tissue homeostasis and tissue repair. Both types of cells contribute to tissue regeneration through the secretion of trophic factors (alone or in the form of microvesicles). This study investigated the isolation and biological properties of microvesicles (MVs) derived from human immortalized MSC line HATMSC1 of adipose tissue origin and EPC line. The human immortalized cell line derived from the adipose tissue of a patient with venous stasis was established in our laboratory using the hTERT and pSV402 plasmids. The human EPC line originating from cord blood (HEPC-CB.1) was established in our previous studies. Microvesicles were isolated through a sequence of centrifugations. Analysis of the protein content of both populations of microvesicles, using the Membrane-Based Antibody Array and Milliplex ELISA showed that isolated microvesicles transported growth factors and pro- and antiangiogenic factors. Analysis of the miRNA content of isolated microvesicles revealed the presence of proangiogenic miRNA (miR-126, miR-296, miR-378, and miR-210) and low expression of antiangiogenic miRNA (miR-221, miR-222, and miR-92a) using real-time RT-PCR with the TaqMan technique. The isolated microvesicles were assessed for their effect on the proliferation and proangiogenic properties of cells involved in tissue repair. It was shown that both HEPC-CB.1- and HATMSC1-derived microvesicles increased the proliferation of human endothelial cells of dermal origin and that this effect was dose-dependent. In contrast, microvesicles had a limited impact on the proliferation of fibroblasts and keratinocytes. Both types of microvesicles improved the proangiogenic properties of human dermal endothelial cells, and this effect was also dose-dependent, as shown in the Matrigel assay. These results confirm the hypothesis that microvesicles of HEPC-CB.1 and HATMSC1 origin carry proteins and miRNAs that support and facilitate angiogenic processes that are important for cutaneous tissue regeneration.

Amniotic Stem Cell-Conditioned Media for the Treatment of Nerve and Muscle Pathology: A Systematic Review

2021 ◽  
Author(s):  
Chukwuweike Gwam ◽  
Ahmed Emara ◽  
Nequesha Mohamed ◽  
Noor Chughtai ◽  
Johannes Plate ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Damage ◽  
Conditioned Media ◽  
Nerve Tissue ◽  
Muscle Pathology ◽  
Loss Of Function ◽  
Cell Based Therapy

Muscle and nerve tissue damage can elicit a significant loss of function and poses as a burden for patients and healthcare providers. Even for tissues, such as the peripheral nerve and skeletal muscle, that harbor significant regenerative capacity, innate regenerative processes often lead to less than optimal recovery and residual loss of function. The reasons for poor regeneration include significant cell damage secondary to oxidative stress, poor recruitment of resident stem cells, and an unfavorable microenvironment for tissue regeneration. Stem cell-based therapy was once thought as a potential therapy in tissue regeneration, due to its self-renewal and multipotent capabilities. Early advocates for cellular-based therapy pointed to the pluripotent nature of stem cells, thus eluding to its ability to differentiate into resident cells as the source of its regenerative capability. However, increasing evidence has revealed a lack of engraftment and differentiation of stem cells, thereby pointing to stem cell paracrine activity as being responsible for its regenerative potential. Stem cell-conditioned media houses biomolecular factors that portray significant regenerative potential. Amniotic-derived stem cell-conditioned media (AFS-CM) has been of particular interest because of its ease of allocation and in vitro culture. The purpose of this review is to report the results of studies that assess the role of AFS-CM for nerve and muscle conditions. In this review, we will cover the effects of AFS-CM on cellular pathways, genes, and protein expression for different nerve and muscle cell types.

Overview: Autologous Peripheral Blood Mononuclear Cells

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Petrungaro A ◽  
◽  
Scudo F ◽  
Quartarone E ◽  
◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Tissue Repair ◽  
Mononuclear Cells ◽  
Mononuclear Phagocyte ◽  
Tendon Tissue ◽  
Central Importance ◽  
Peripheral Blood Mononuclear ◽  
Avant Garde ◽  
Blood Mononuclear Cells ◽  
A Cell

The implant of autologous mononuclear cells is an avant-garde method based on the use of a cell population within our body to regenerate tissues that have been damaged by various pathological events. The biological assumption is the richness and complexity of biochemical and cellular phenomena inherent in both organism response to damage and tissue regeneration. The key role is played by the mononuclear phagocyte system which regulates and modulates the activity of mesenchymal stem cells capable of differentiating and providing tissue repair. This system does not only have a traditional “scavenger” function within the immune system, but it is also of central importance in the modulation and activation of the response to tissue damage, be it traumatic, surgical, or degenerative. In this review we summarize the main features of this method and the most common uses in clinical practice where the interest is growing considering both the powerful, rapid and documented regenerative response of the various “target” tissues: vascular, cartilage, bone, muscle and tendon tissue.

Abstract P477: A Novel SMYD1 Variant (c.302A>G) Leads To Dilated Cardiomyopathy And Biventricular Heart Failure.

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Marta Szulik ◽  
Miguel Reyes-Mugica ◽  
Daniel F Marker ◽  
Lina Ghaloul-Gonzalez ◽  
Sarah Franklin
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Cardiac Tissue ◽  
De Novo ◽  
Cardiac Development ◽  
Left Ventricular ◽  
Histopathological Analysis ◽  
Loss Of Function ◽  
Adult Mice ◽  
Heterozygous Variant

The lysine methyltransferase SMYD1 was first identified in mice and shown to be important for embryonic cardiac development. Subsequently, we reported the first analysis of SMYD1 in adult myocardium and demonstrated that cardiomyocyte-specific loss of SMYD1 lead to progressive cardiac hypertrophy and heart failure, and showed that this enzyme is necessary to maintain metabolic homeostasis through transcriptional regulation of mitochondrial energetics in adult mice. While SMYD1 has been the subject of several additional studies in zebrafish and mice, since it was first identified, only in the last few years have human patients been identified with variants in the SMYD1 gene thought to be responsible for their cardiomyopathies. Specifically, two patients have been identified to date, the first patient displaying hypertrophic cardiomyopathy had a de novo heterozygous variant (c.814T>C) and the second patient with left ventricular non-compaction cardiomyopathy and arrhythmias had a truncating heterozygous variant (c.675delA). Here we report a third patient with biventricular heart failure containing a homozygous variant (c.302A>G; p.Asn101S) in the SMYD1 gene which was identified by a whole exome sequencing. Our histopathological analysis of cardiac tissue and skeletal muscle from the proband showed abnormalities in myofibrillar organization in both cardiac and skeletal muscle suggesting that SMYD1 is necessary for sarcomere assembly and organization. In addition, we observe markedly abnormal myocardium with extensive fibrosis and multifocal calcification, and our ultrastructural (EM) analysis revealed presence of abnormal mitochondria with reduced and irregular or lost cristae. Lastly, we have performed structural modeling of SMYD1 containing the p.Asn101Ser variant (N101S) and report how this variant may affect the enzymatic activity of SMYD1 due to its proximity to the substrate binding site. The identification of this novel variant constitutes the third patient with a SMYD1 variant displaying cardiomyopathy and provides insights into the molecular functionality of this protein. In addition, this is the first analysis of tissue from a patient expressing a SMYD1 variant which provides critical insights into the role of SMYD1 in the heart and how loss of function mutations can effect cardiac physiology.

scholarly journals Neuro–Immune Cell Units: A New Paradigm in Physiology

2019 ◽  
Vol 37 (1) ◽  
pp. 19-46 ◽  
Author(s):  
Cristina Godinho-Silva ◽  
Filipa Cardoso ◽  
Henrique Veiga-Fernandes
Keyword(s):  
Adipose Tissue ◽  
Paradigm Shift ◽  
Tissue Repair ◽  
Immune Cell ◽  
The Body ◽  
New Paradigm ◽  
Environmental Signals ◽  
The Past ◽  
Physiological Processes ◽  
The Impact

The interplay between the immune and nervous systems has been acknowledged in the past, but only more recent studies have started to unravel the cellular and molecular players of such interactions. Mounting evidence indicates that environmental signals are sensed by discrete neuro–immune cell units (NICUs), which represent defined anatomical locations in which immune and neuronal cells colocalize and functionally interact to steer tissue physiology and protection. These units have now been described in multiple tissues throughout the body, including lymphoid organs, adipose tissue, and mucosal barriers. As such, NICUs are emerging as important orchestrators of multiple physiological processes, including hematopoiesis, organogenesis, inflammation, tissue repair, and thermogenesis. In this review we focus on the impact of NICUs in tissue physiology and how this fast-evolving field is driving a paradigm shift in our understanding of immunoregulation and organismal physiology.

scholarly journals Fndc5 loss‐of‐function attenuates exercise‐induced browning of white adipose tissue in mice

2019 ◽  
Vol 33 (5) ◽  
pp. 5876-5886 ◽  
Author(s):  
Yan Xiong ◽  
Zihuan Wu ◽  
Bin Zhang ◽  
Chao Wang ◽  
Fengyi Mao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Loss Of Function ◽  
Exercise Induced

scholarly journals Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Tobias Weinberger ◽  
Dena Esfandyari ◽  
Denise Messerer ◽  
Gulce Percin ◽  
Christian Schleifer ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Immune Cells ◽  
Transcriptional Response ◽  
Developmental Origins ◽  
Adult Mice ◽  
Single Cell Rna Sequencing ◽  
Mapping Analysis ◽  
Health And Disease ◽  
Arterial Inflammation ◽  
Cellular Identity

Abstract Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.

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