• Just as plant cells respond to injury by undergoing callus formation via dedifferentiation, some animal models dedifferentiate their cells to form blastema, which are analogous to plant calluses, after limb amputation. (wikipedia.org)
  • In mammals, a limb amputation or spinal cord transection is followed by inflammation and fibrotic scarring that leaves the animal with a permanent disability. (frontiersin.org)
  • Lowered Notch1 expression resulted in no tadpole tail regeneration, and induced Notch1 expression was able to partially rescue tail regeneration in the form of notochord and spinal cord (but very little musculature. (wikipedia.org)
  • But in mammals, including humans, some tissues (e.g., heart muscle) are more resistant to regeneration. (cshlpress.com)
  • The contributors discuss the dramatic molecular and cellular changes that occur when a regeneration program is initiated, the progenitor cells and morphogenic signals involved, the formation of a blastema, the roles of reprogramming and polyploidy, the diversity of cell fates, the integration of new structures with existing body parts, and our current understanding of why some structures are more resistant to regeneration than others. (cshlpress.com)
  • The importance of technologies (e.g., single-cell RNA-seq) that have been instrumental in deciphering various aspects of regeneration in recent years is emphasized throughout. (cshlpress.com)
  • This volume is therefore essential reading for molecular, cell, and developmental biologists studying regeneration in animals, as well as for all interested in the development of regenerative therapies for clinical application. (cshlpress.com)
  • While most studies on limb regeneration have focused on animals such as the axolotle, which demonstrates natural regrowth capabilities, the newly reported study in frogs could help direct future research towards limb regeneration in mammals, including humans. (genengnews.com)
  • Many creatures-including salamanders, starfish, crabs, and lizards-have the capability of full regeneration of at least some limbs. (genengnews.com)
  • However, loss of a large and structurally complex limb-an arm or leg-can not be restored by any natural process of regeneration in humans or other mammals. (genengnews.com)
  • Unidirectional regeneration in the basal chordate Ciona intestinalis involves the proliferation of adult stem cells residing in the branchial sac vasculature and the migration of progenitor cells to the site of distal injury. (biomedcentral.com)
  • However, after the Ciona body is bisected, regeneration occurs in the proximal but not in the distal fragments, even if the latter include a part of the branchial sac with stem cells. (biomedcentral.com)
  • siRNA-mediated gene knockdown showed that hsp70 and dnaJb4, but not bag3, are required for progenitor cell targeting and distal regeneration. (biomedcentral.com)
  • Heat shock treatment of distal body fragments activated hsp70 and dnaJb4 expression indicative of a stress response, induced cell proliferation in branchial sac vasculature cells, and promoted distal regeneration. (biomedcentral.com)
  • The stress response is absent from distal fragments, but can be induced by a heat shock, which activates cell division in the branchial sac vasculature and promotes distal regeneration. (biomedcentral.com)
  • This study demonstrates the importance of a stress response for stem cell activation and regeneration in a basal chordate, which may have implications for understanding the limited regenerative activities in other animals, including vertebrates. (biomedcentral.com)
  • In vertebrates with limited regeneration capacities, such as mammals, wound repair typically terminates in fibrotic scar formation and is not followed by regeneration. (biomedcentral.com)
  • The formation of new cells, tissues, and organs enables animals to recover from day-to-day wear and tear, injury, and disease. (cshlpress.com)
  • Therefore, we propose that damage to and subsequent release of mtDNA elicits a protective signalling response that enhances nDNA repair in cells and tissues, suggesting that mtDNA is a genotoxic stress sentinel. (regenerativemedicine.net)
  • While it can be induced in a laboratory setting through processes like direct reprogramming and the production of induced pluripotent stem cells, endogenous dedifferentiation processes also exist as a component of wound healing mechanisms. (wikipedia.org)
  • We hypothesized that kickstarting a limb-building routine required two components acting at a very early initiating stage of the process: first, an enclosed and permissive microenvironment that enables the wound cells to control the biochemical milieu following injury and, second, an instructive set of signals that specifically trigger a limb-building program. (genengnews.com)
  • In both processes, rapid proliferation gives rise to new tissue, cell fate has to be specified within that tissue, and distinct positional identities have to be established to generate a properly patterned structure. (frontiersin.org)
  • In the 1940s C. H. Waddington created the "Epigenetic Landscape", a diagrammatic representation of cell fate from less differentiated to more differentiated cell types. (wikipedia.org)
  • Our recent work in adult Xenopus showed a significant degree of outgrowth induced by progesterone," they wrote. (genengnews.com)
  • Regrowth of legs and arms remains the province of animals such as salamanders, or perhaps superheroes. (genengnews.com)
  • This is in contrast to differentiation, where differences in gene expression, morphology, or physiology arise in a cell, making its function increasingly specialized. (wikipedia.org)
  • The upregulation of HSP70 chaperone genes was verified and their expression confirmed in BS vasculature cells previously identified as stem and progenitor cells. (biomedcentral.com)
  • This suggests an increase in cell potency, meaning that, following dedifferentiation, a cell may possess the ability to re-differentiate into more cell types than it did prior to dedifferentiation. (wikipedia.org)
  • Thousands of copies of the circular mtDNA are present in most cell types that are packaged by TFAM into higher-order structures called nucleoids1. (regenerativemedicine.net)
  • Dedifferentiation (pronounced dē-ˌdi-fə-ˌren-chē-ˈā-shən) is a transient process by which cells become less specialized and return to an earlier cell state within the same lineage. (wikipedia.org)
  • This repressor would be able to keep cells undifferentiated during development. (wikipedia.org)
  • In addition, mtDNA stress in TFAM-deficient mouse melanoma cells produces tumours that are more resistant to doxorubicin in vivo. (regenerativemedicine.net)
  • While it can be induced in a laboratory setting through processes like direct reprogramming and the production of induced pluripotent stem cells, endogenous dedifferentiation processes also exist as a component of wound healing mechanisms. (wikipedia.org)
  • The absence of this single gene, called p21, confers a healing potential in mice long thought to have been lost through evolution and reserved for creatures like flatworms, sponges, and some species of salamander. (eurekalert.org)
  • Lizards cannot naturally regenerate limbs but are the closest known relatives of mammals capable of epimorphic tail regrowth. (bvsalud.org)
  • Pseudotime trajectory analyses suggest spp1+-activated fibroblasts as blastema cell sources, with subsets exhibiting sulf1 expression and chondrogenic potential. (bvsalud.org)
  • However, the markers selected to represent dedifferentiation can differ according to tissue and cell types that are being studied. (wikipedia.org)
  • Green anole lizard (Anolis carolinensis) blastemas contain fibroblastic connective tissue cells (FCTCs), which respond to hedgehog signaling to create cartilage in vivo. (bvsalud.org)
  • 2) Methods: By testing two adapted tissue dissociation protocols and two optimized media formulations, lizard tail FCTCs were pelleted in vitro and grown in a micromass blastema organoid culture. (bvsalud.org)
  • Pathologies, as atherosclerosis, cardiac fibrosis, and cardiomyopathy, are often linked to the failure of cardiovascular tissue cells to reenter the cell cycle, namely, senescence, due to endogenous or exogenous causes. (hindawi.com)
  • This is in contrast to differentiation, where differences in gene expression, morphology, or physiology arise in a cell, making its function increasingly specialized. (wikipedia.org)
  • Here, the concept of a marble moving downhill through various paths is used to represent cell decision-making and cell potency, thus visualizing how cells can take different paths of differentiation to reach a final state. (wikipedia.org)
  • Unlike typical mammals, which heal wounds by forming a scar, these mice begin by forming a blastema, a structure associated with rapid cell growth and de-differentiation as seen in amphibians. (eurekalert.org)
  • Regenerated lizard tails form ependymal tubes (ETs) that, like embryonic tail neural tubes (NTs), induce cartilage differentiation in surrounding cells via sonic hedgehog (Shh) signaling. (bvsalud.org)
  • In vivo delivery of TK-NTR and administration of prodrugs led to the effective killing of both targeted cells and surrounding tumor cells via TK-NTR-mediated conversion of co-delivered prodrugs into active cytotoxic agents. (regenerativemedicine.net)
  • In vivo evaluation of the bystander effect in mouse models demonstrated that for effective therapy, at least 1% of tumor cells need to be delivered with TK-NTR-encoding MCs. (regenerativemedicine.net)
  • The results indicate a hierarchy of phagocyte-induced fibroblast gene activations during lizard blastema formation, culminating in sulf1+ pro-chondrogenic populations singularly responsive to Hedgehog signaling. (bvsalud.org)
  • These results suggest that MC delivery via microvesicles can mediate gene transfer to an extent that enables effective prodrug conversion and tumor cell death such that it comprises a promising approach to cancer therapy. (regenerativemedicine.net)
  • Both NTs and ETs contain neural stem cells (NSCs), but only embryonic NSC populations differentiate into roof plate identities when protected from endogenous Hedgehog signaling. (bvsalud.org)
  • Additionally, we dissect the effects of aging on the cardiac endogenous and exogenous reservoirs of stem cells. (hindawi.com)
  • This review will focus on the cardiovascular pathologies correlated to senescence, the effect of aging on the cardiac endogenous resources of stem cells, and the potential strategies of regenerative medicine to be applied to maintain the heart younger and healthier. (hindawi.com)
  • The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. (mdpi.com)
  • However, the mechanisms regulating lizard blastema formation and chondrogenesis remain unclear. (bvsalud.org)
  • The combined effects of an increase in highly regenerative cells and apoptosis may allow the cells of these organisms to divide rapidly without going out of control and becoming cancerous," Heber-Katz said. (eurekalert.org)
  • Tail blastema, but not limb, fibroblasts express sulf1 and form cartilage under Hedgehog signaling regulation. (bvsalud.org)
  • Senescence in adult tissues can be classified in two main subcategories, based on the underlying molecular mechanism: replicative (or intrinsic), caused by telomere shortening, and stress-induced, in response to reactive oxygen species (ROS) and/or oncogenes [ 7 - 9 ]. (hindawi.com)
  • MMP degrades proteins in the extracellular matrix [1] of a cell, resulting in the destabilization of the differentiated cell identity. (wikipedia.org)
  • Activation of the cellular senescence genetic program prompts a series of molecular changes, mostly affecting cell cycle, extracellular matrix (ECM), secretion of growth factors, and inflammatory mediators. (hindawi.com)
  • The distal region of the dental lamina interacts with mesenchymal cells and forms a cup that is composed of the outer dental epithelium and the inner dental epithelium. (nature.com)
  • The mesenchymal cells facing the inner dental epithelium differentiate into a dental papilla. (nature.com)
  • In fact, the researchers saw an increase in apoptosis in MRL mice - also known as programmed cell death - the cell's self-destruct mechanism that is often switched on when DNA has been damaged. (eurekalert.org)
  • Just as plant cells respond to injury by undergoing callus formation via dedifferentiation, some animal models dedifferentiate their cells to form blastema, which are analogous to plant calluses, after limb amputation. (wikipedia.org)
  • The formation of new cells, tissues, and organs enables animals to recover from day-to-day wear and tear, injury, and disease. (cshlpress.com)
  • Here, single-cell RNA sequencing analysis of regenerating lizard tails identifies fibroblast and phagocyte populations linked to cartilage formation. (bvsalud.org)
  • Depletion of phagocytes inhibits blastema formation, but treatment with pericytic phagocyte-conditioned media rescues blastema chondrogenesis and cartilage formation in amputated limbs. (bvsalud.org)
  • While it is commonly accepted as an aging-related phenomenon, senescence might happen also during the embryonic development with the biological meaning of replacing transient structures or specific cell types with other ones [ 3 - 5 ]. (hindawi.com)
  • At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. (hindawi.com)
  • Dedifferentiation (pronounced dē-ˌdi-fə-ˌren-chē-ˈā-shən) is a transient process by which cells become less specialized and return to an earlier cell state within the same lineage. (wikipedia.org)
  • The dental papilla cells then further differentiate into odontoblasts. (nature.com)
  • This suggests an increase in cell potency, meaning that, following dedifferentiation, a cell may possess the ability to re-differentiate into more cell types than it did prior to dedifferentiation. (wikipedia.org)
  • Notch proteins are part of an intercellular signaling pathway responsible for regulating interactions between cells that are physically next to one another by binding to other notch proteins. (wikipedia.org)
  • Meanwhile, cellular studies ongoing at Wistar revealed that MRL cells behaved very differently than cells from "non-healer" mouse strains in culture. (eurekalert.org)
  • However, an in vitro model of the blastema has not previously been achieved in culture. (bvsalud.org)
  • 3) Results: Using an optimized serum-free media and a trypsin- and collagenase II-based dissociation protocol, micromass blastema organoids were formed. (bvsalud.org)
  • Khamilia Bedebaeva, M.D., Ph.D., having studied genetic effects following the Chernobyl reactor radiation accident, noticed immediately that these cells were atypical, showing profound differences in cell cycle characteristics and DNA damage. (eurekalert.org)
  • This led Andrew Snyder, Ph.D., to explore the DNA damage pathway and its effects on cell cycle control. (eurekalert.org)
  • Snyder found that p21, a cell cycle regulator, was consistently inactive in cells from the MRL mouse ear. (eurekalert.org)
  • In normal cells, p21 acts like a brake to block cell cycle progression in the event of DNA damage, preventing the cells from dividing and potentially becoming cancerous," Heber-Katz said. (eurekalert.org)
  • Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. (hindawi.com)
  • Additionally, an estimated 1.6 million people (2005 data) are living with limb injury or disease induced amputations and the number is expected to double by 2050. (nih.gov)
  • However, others say that it can be used to describe a general increase in cell potency. (wikipedia.org)