Most but not all phyla include examples of species that are able to regenerate large sections of the body plan. The mechanisms underlying regeneration on this scale are currently being studied in a variety of contexts in both vertebrates and invertebrates. Regeneration generally involves the formation of a wound epithelium after transection or injury, followed by the generation of regenerative progenitor cells and morphogenesis to give the regenerate. Common mechanisms may exist in relation to each of these aspects. For example, the initial proliferation of progenitor cells often depends on the nerve supply, whereas morphogenesis reflects the generation of positional disparity between adjacent cells-the principle of intercalation. These mechanisms are reviewed here across a range of contexts. We also consider the evolutionary origins of regeneration and how regeneration may relate to both agametic reproduction and to ontogeny.

Abstract.  Peptide nanostructures containing bioactive signals offer exciting novel therapies of broad potential impact in regenerative medicine. These nanostructures can be designed through self‐assembly strategies and supramolecular chemistry, and have the potential to combine bioactivity for multiple targets with biocompatibility. It is also possible to multiplex their functions by using them to deliver proteins, nucleic acids, drugs and cells. In this review, we illustrate progress made in this new field by our group and others using peptide‐based nanotechnology. Specifically, we highlight the use of self‐assembling peptide amphiphiles towards applications in the regeneration of the central nervous system, vasculature and hard tissue along with the transplant of islets and the controlled release of nitric oxide to prevent neointimal hyperplasia. Also, we discuss other self‐assembling oligopeptide technology and the progress made with these materials towards the development of potential therapies.

Hepatic ischemia reperfusion injury (IRI) remains a major obstacle in liver resection and transplantation surgery, especially in diseased organs. Human mesenchymal stromal cells (MSCs) are reported to acutely alleviate hepatic IRI in mice by releasing bioactive membrane-enclosed extracellular vesicles (EVs), but the long-term effects of MSC-derived EV on hepatic IRI are unknown. Given the considerable differentiation capacity of fibroblasts (FBs) during wound healing and their morphological similarities with MSC, the present study aimed to investigate the potential of these two cell types and their cell-derived EV in attenuating liver damage after IRI. EVs were isolated and purified from the supernatant of MSC and FB cultures and, subsequently, characterized by electron microscopy, nanoparticle tracking analysis, and western blot. Liver injury and organ regeneration in a murine in vivo model of IRI were assessed by serum transaminase levels, histopathology, and immunohistochemistry. Changes in expression of inflammation-associated genes within liver tissue were evaluated by reverse transcriptase quantitative polymerase chain reaction. MSC, MSC-derived EV, FB, and FB-derived EV were systemically administered before hepatic IRI. We found that MSC and MSC-derived EV decreased serum transaminase levels, reduced hepatic necrosis, increased the amount of Ki67-positive hepatocytes, and repressed the transcription of inflammation-associated genes. Although they had no impact on organ damage, FB and FB-derived EV showed some regenerative potential in the late phase of hepatic IRI. Compared to FB, MSC and their derived EV had a stronger potential to attenuate liver damage and improve organ regeneration after hepatic IRI. These results suggest that the key therapeutic factors are located within EV.

The liver centralizes the systemic metabolism and thus controls and modulates the functions of the central and peripheral nervous systems, the immune system, and the endocrine system. In addition, the liver intervenes between the splanchnic and systemic venous circulation, determining an abdominal portal circulatory system. The liver displays a powerful regenerative potential that rebuilds the parenchyma after an injury. This regenerative mission is mainly carried out by resident liver cells. However, in many cases this regenerative capacity is insufficient and organ failure occurs. In normal livers, if the size of the liver is at least 30% of the original volume, hepatectomy can be performed safely. In cirrhotic livers, the threshold is 50% based on current practice and available data. Typically, portal vein embolization of the part of the liver that is going to be resected is employed to allow liver regeneration in two-stage liver resection after portal vein occlusion (PVO). However, hepatic resection often cannot be performed due to advanced disease progression or because it is not indicated in patients with cirrhosis. In such cases, liver transplantation is the only treatment possibility, and the need for transplantation is the common outcome of progressive liver disease. It is the only effective treatment and has high survival rates of 83% after the first year. However, donated organs are becoming less available, and mortality and the waiting lists have increased, leading to the initiation of living donor liver transplantations. This type of transplant has overall complications of 38%. In order to improve the treatment of hepatic injury, much research has been devoted to stem cells, in particular mesenchymal stem cells (MSCs), to promote liver regeneration. In this review, we will focus on the advances made using MSCs in animal models, human patients, ongoing clinical trials, and new strategies using 3D organoids.

While many vertebrates can regenerate both damaged neurons and severed axons in the central nervous system (CNS) following injury, others, including all birds and mammals, have lost this ability for reasons that are still unclear. The repeated evolutionary loss of regenerative competence seems counterintuitive, and any explanation must account for the fact that regenerative competence is lost in both cold-blooded and all warm-blooded clades, that both injury-induced neurogenesis and axonal regeneration tend to be lost in tandem, and that mammals have evolved dedicated gene regulatory networks to inhibit injury-induced glia-to-neuron reprogramming. Here, different hypotheses that have been proposed to account for evolutionary loss of regenerative competence are discussed in the light of new insights obtained into molecular mechanisms that control regeneration in the central nervous system. These include pleiotropic effects of continuous growth, enhanced thyroid hormone signaling, prevention of neoplasia, and improved memory consolidation. Recent evidence suggests that the most compelling hypothesis, however, may be selection for greater resistance to the spread of intra-CNS infections, which has led to both enhanced reactive gliosis and a loss of injury-induced neurogenesis and axonal regeneration. Means of testing these hypotheses, and additional data that are urgently needed to better understand the evolutionary pressures and mechanisms driving loss of regenerative competence, are also discussed.

Elucidating the molecular circuitry that regulates regenerative responses in mammals has recently attracted considerable attention because of its emerging impact on modern bioengineering, tissue replacement technologies, and organ transplantation. The liver is one of the few organs of the adult body that exhibits a prominent regenerative capacity in response to toxic injury, viral infection, or surgical resection. Over the years, mechanistic insights into the liver's regenerative potential have been provided by rodent models of chemical liver injury or surgical resection that faithfully recapitulate hallmarks of human pathophysiology and trigger robust hepatocyte proliferation leading to organ restoration. The advent of mouse transgenics has undeniably catalyzed the wider application of such models for researching liver pathobiology. This article provides a comprehensive overview of the most reliable and widely applied murine models of liver regeneration and also discusses helpful hints, considerations, and limitations related to the use of these models in liver regeneration studies. Curr. Protoc. Mouse Biol. 3:141‐170 © 2013 by John Wiley & Sons, Inc.

regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete after which Regeneration in biology is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete after which the n Regeneration in biology is the process of renewal, restoration, and tissue…

research because of their unusual ability to regenerate body parts, including limbs, gills and parts of their eyes and brains. The species is also used as a model The axolotl ( ; from Classical Nahuatl: āxōlōtl [aːˈʃoːloːtɬ] ; Ambystoma mexicanum) is a species of mole salamander. It is neotenic, reaching sexual maturity without undergoing metamorphosis, and the adults remain fully aquatic with obvious external gills. Axolotls may be difficult to distinguish from the larval stage of other neotenic adult mole salamanders, in particular the tiger salamander, o The characteristic of the axolotl that attracts the most attention is its unusual healing ability; axolotls do not heal by scarring but are instead capable of tissue regeneration. Entire lost appendages, such as the limbs and tail, can regrow over a period of months. In certain cases, more vital structures can be regrown, such as tissues of the eye and heart. Axolotls can even restore parts of their central nervous system, including non-vital parts of their brains. They can readily accept transplants from other individuals—including eyes and parts of the brain—restoring these "alien organs" to full functionality. In special cases, axolotls have been able to repair a damaged limb while also generating an additional limb, resulting in an extra appendage that makes them attractive to pet owners as a novelty. The three basic requirements for limb regeneration in an axolotl are: (1) the formation of a wound epithelium, (2) the presence of nerve signaling, and (3) the presence of cells from the different axes (lines of orientation) of the affected limb. An epidermis quickly forms to seal the site of the wound. Over the next few days, the cells of the wound epidermis divide and grow, forming a blastema, at which point the wound is ready to heal and undergo patterning to form the new limb. It is believed that during limb generation, axolotls have a special system to regulate their internal macrophage level and suppress inflammation, as scarring would prevent proper healing and regeneration. However, this belief has been questioned by other studies. A fundamental growth structure credited for the axolotl's ability to regenerate whole limbs in early development is the apical ectodermal ridge (AER), with the apical ectodermal cap (AEC). The AER initiates the growth of appendages in embryos by signaling how they are shaped and extended. Ectodermal cells are needed to form limbs in most tetrapods, amphibians and humans, but unlike most other animals the AEC in the axolotl can send signals through growth hormones to activate blastema cells, which can rebuild whole amputated or damaged limbs or organs.

arranged in series according to their ability to respond to electric currents of short … mechanical stimuli is regained sooner than the ability to reply to changes as rapid as those … degen- eration. As nerves have the power to regenerate, they may recover from even such an