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 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 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 Comparative Aspects of Annelid Regeneration: Towards Understanding the Mechanisms of Regeneration

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1148
Author(s):  
Roman P. Kostyuchenko ◽  
Vitaly V. Kozin
Keyword(s):  
Tissue Regeneration ◽  
Molecular Basis ◽  
The Other ◽  
Whole Body ◽  
Descriptive Data ◽  
Transcriptomic Data ◽  
Levels Of Organization ◽  
Ability To Regenerate ◽  
Different Levels

The question of why animals vary in their ability to regenerate remains one of the most intriguing questions in biology. Annelids are a large and diverse phylum, many members of which are capable of extensive regeneration such as regrowth of a complete head or tail and whole-body regeneration, even from few segments. On the other hand, some representatives of both of the two major annelid clades show very limited tissue regeneration and are completely incapable of segmental regeneration. Here we review experimental and descriptive data on annelid regeneration, obtained at different levels of organization, from data on organs and tissues to intracellular and transcriptomic data. Understanding the variety of the cellular and molecular basis of regeneration in annelids can help one to address important questions about the role of stem/dedifferentiated cells and “molecular morphallaxis” in annelid regeneration as well as the evolution of regeneration in general.

scholarly journals Tissue Regeneration: The Dark Side of Opioids

2021 ◽  
Vol 22 (14) ◽  
pp. 7336
Author(s):  
Cécile Dromard Berthézène ◽  
Lise Rabiller ◽  
Géraldine Jourdan ◽  
Béatrice Cousin ◽  
Luc Pénicaud ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Standard Of Care ◽  
Regenerative Process ◽  
Dark Side ◽  
Nerve Activity ◽  
And Function ◽  
Scar Healing ◽  
Inflammatory Effect

Opioids are regarded as among the most effective analgesic drugs and their use for the management of pain is considered standard of care. Despite their systematic administration in the peri-operative period, their impact on tissue repair has been studied mainly in the context of scar healing and is only beginning to be documented in the context of true tissue regeneration. Indeed, in mammals, growing evidence shows that opioids direct tissue repair towards scar healing, with a loss of tissue function, instead of the regenerative process that allows for recovery of both the morphology and function of tissue. Here, we review recent studies that highlight how opioids may prevent a regenerative process by silencing nociceptive nerve activity and a powerful anti-inflammatory effect. These data open up new perspectives for inducing tissue regeneration and argue for opioid-restricted strategies for managing pain associated with tissue injury.

scholarly journals Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia

2020 ◽  
Author(s):  
Lauritz H. Kennedy ◽  
Emilie R. Glesaaen ◽  
Vuk Palibrk ◽  
Marco Pannone ◽  
Wei Wang ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Subventricular Zone ◽  
Tissue Repair ◽  
Microglial Activation ◽  
Neural Progenitor Cells ◽  
Transcriptional Response ◽  
Current Treatment ◽  
Promising Therapeutic Target ◽  
Hypoxia Ischemia

AbstractNeonatal cerebral hypoxia-ischemia (HI) is the leading cause of death and disability in newborns with the only current treatment option being hypothermia. An increased understanding of the pathways that facilitate tissue repair after HI can aid the development of better treatments. Here we have studied the role of lactate receptor HCAR1 (Hydroxycarboxylic acid receptor 1) in tissue repair after HI in mice. We show that HCAR1 knockout (KO) mice have reduced tissue regeneration compared with wildtype (WT) mice. Further, proliferation of neural progenitor cells and microglial activation were impaired after HI. Transcriptome analysis showed a strong transcriptional response to HI in the subventricular zone of WT mice involving about 7300 genes. In contrast, the HCAR1 KO mice showed a very modest response to HI, involving about 750 genes. Notably, fundamental processes involved in tissue repair such as cell cycle and innate immunity were dysregulated in HCAR1 KO. Taken together, our data suggest that HCAR1 is a key transcriptional regulator of the pathways that promote tissue regeneration after HI. Thus, HCAR1 could be a promising therapeutic target in the treatment of neonatal HI and other forms of brain ischemia.

Lifting the veil on macrophage diversity in tissue regeneration and fibrosis

2019 ◽  
Vol 4 (40) ◽  
pp. eaaz0749 ◽  
Author(s):  
Catia T. Perciani ◽  
Sonya A. MacParland
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Tissue Regeneration ◽  
Tissue Repair ◽  
Single Cell Rna Sequencing ◽  
The Veil

Sommerfeld et al. have used single-cell RNA sequencing to unravel the role of macrophages in driving tissue repair and fibrosis.

scholarly journals Role of CD4 in thymocyte selection and maturation.

1989 ◽  
Vol 169 (6) ◽  
pp. 2085-2096 ◽  
Author(s):  
J C Zuñiga-Pflücker ◽  
S A McCarthy ◽  
M Weston ◽  
D L Longo ◽  
A Singer ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Decisive Role ◽  
Class Ii ◽  
Double Positive ◽  
Adult Mice

We examined the possible role of CD4 molecules during in vivo and in vitro fetal thymic development. Our results show that fetal thymi treated with intact anti-CD4 mAbs fail to generate CD4 single-positive T cells, while the generation of the other phenotypes remains unchanged. Most importantly, the use of F(ab')2 and Fab anti-CD4 mAb gave identical results, i.e., failure to generate CD4+/CD8- T cells, with no effect on the generation of CD4+/CD8+ T cells. Since F(ab')2 and Fab anti-CD4 fail to deplete CD4+/CD8- in adult mice, these results strongly argue that the absence of CD4+/CD8- T cells is not due to depletion, but rather, is caused by a lack of positive selection, attributable to an obstructed CD4-MHC class II interaction. Furthermore, we also observed an increase in TCR/CD3 expression after anti-CD4 (divalent or monovalent) mAb treatment. The TCR/CD3 upregulation occurs in the double-positive population, and may result from CD4 signaling after mAb engagement, or may be a consequence of the blocked CD4-class II interactions. One proposed model argues that the CD3 upregulation occurs in an effort to compensate for the reduction in avidity or signaling that is normally provided by the interaction of the CD4 accessory molecule and its ligand. As a whole, our findings advocate that CD4 molecules play a decisive role in the differentiation of thymocytes.

scholarly journals Mimicking growth factors: role of small molecule scaffold additives in promoting tissue regeneration and repair

RSC Advances ◽  
2019 ◽  
Vol 9 (32) ◽  
pp. 18124-18146 ◽  
Author(s):  
Nowsheen Goonoo ◽  
Archana Bhaw-Luximon
Keyword(s):  
Growth Factors ◽  
Small Molecules ◽  
Small Molecule ◽  
Tissue Regeneration ◽  
Tissue Repair

Scaffold loaded with small molecules mimicking the action of growth factors for tissue repair.

Loss of Runx1 Perturbs Adult Hematopoiesis and Is Associated with a Myeloproliferative Phenotype.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 227-227
Author(s):  
Joseph D. Growney ◽  
Hirokazu Shigematsu ◽  
Zhe Li ◽  
Benjamin H. Lee ◽  
Jennifer Adelsperger ◽  
...  
Keyword(s):  
Critical Role ◽  
Extramedullary Hematopoiesis ◽  
Loss Of Function ◽  
Hematopoietic Malignancies ◽  
Adult Mice ◽  
Specific Effects ◽  
Myeloid Progenitor ◽  
Blood Neutrophils ◽  
T Cell Maturation

Abstract Homozygous loss of function of Runx1 during murine development results in an embryonic lethal phenotype characterized by a complete lack of definitive hematopoiesis. In light of recent reports of disparate requirements for hematopoietic transcription factors during development as opposed to adult hematopoiesis, we employed a conditional gene targeting strategy to effect loss of Runx1 function in adult mice. In contrast with the critical role of Runx1 during development, Runx1 was not essential for hematopoiesis in the adult hematopoietic compartment, although there were a number of significant hematopoietic abnormalities observed. Runx1 excision had significant lineage specific effects on B- and T-cell maturation, as well as pronounced inhibition of common lymphocyte progenitor production. Runx1 excision also resulted in inefficient platelet production. Of note, Runx1 deficient mice developed a mild myeloproliferative phenotype characterized by an increase in peripheral blood neutrophils, an increase in myeloid progenitor populations, and extramedullary hematopoiesis comprised of maturing myeloid and erythroid elements. These findings indicate that Runx1 deficiency has markedly different consequences during development compared with adult hematopoiesis, and provides insights into the phenotypic manifestations of Runx1 deficiency in hematopoietic malignancies.

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