Regeneration induced in the forelimbs by treatment with vitamin A in the froglets ofRana breviceps

Summary Young froglets ofRana breviceps do not possess the power to regenerate forelimbs after amputation through metacarpals. However, 5 min immersion of limb stumps in an oily solution of 150,000 IU vitamin A palmitate immediately after amputation, and once on each of the 3 subsequent days, induced definite though hypomorphic regeneration in 100% cases.Acknowledgments. This research was supported by a grant from the Council of Scientific and Industrial Research, India.     

Cellular events in denervated limb stumps ofAmbystoma larvae during re-innervation and subsequent regeneration

Summary Amputated, denervatedAmbystoma forelimbs undergo cellular dedifferentiation and slight resorption through 12 days post-amputation. Subsequently, as limb stumps become re-innervated, there occur mitosis, blastema formation, and regeneration. The initial increase in the mitotic index in once-denervated limb stumps is closely correlated with the presence of ingrowing nerve fibres.This work was supported by grant PCM 76-11807 from the National Science Foundation.     

Development of the auditory tympana in the cricketTeleogryllus commodus (Walker): Experiments on regeneration and transplantation

Summary Grafting and regeneration experiments on prothoracic legs of the cricketTeleogryllus commodus (Walker) demonstrate: a) that the legs retain their identity, as indicated by formation of tympanal cuticle in the adult, when transplanted to the site of a mesothoracic leg in immature animals, and b) that the presence of tympanal cuticle on a regenerate leg depends on the instar of amputation.I thank Mike Bate for the helpful discussion throughout the project and Carmen Vilcins for excellent technical assistance.     

Effect of testosterone and 17-beta estradiol on limb regeneration in the newt, Notophthalmus viridescens

Gonadectomy, or injections of testosterone or 17-beta estradiol, had no apparent effect on the rate of regeneration or histological appearance of limb regenerates in the newt, Notophthalmus viridescens. Neither promotion, nor inhibition of limb regeneration was observed.     

Effect of sublethal concentrations of sumithion on limb regeneration of fresh water field crab Oziotelphusa senex senex

The initiation and progress of regeneration following the removal of the left 4th walking leg were altered in the crab (Oziotelphusa senex senex) by exposure to sumithion. Depending on the concentration used, sumithion caused a complete inhibition of regeneration, a delay of initiation of limb bud development or a reduction of limb bud growth rate. Crustacean limb regeneration can also be used as a sensitive bioassay for studying the effects of environmental pollutants.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

The Xenopus tadpole is a favourable organism for regeneration research because it is suitable for a wide range of micromanipulative procedures and for a wide range of transgenic methods. Combination of these techniques enables genes to be activated or inhibited at specific times and in specific tissue types to a much higher degree than in any other organism capable of regeneration. Regenerating systems include the tail, the limb buds and the lens. The study of tail regeneration has shown that each tissue type supplies the cells for its own replacement: there is no detectable de-differentiation or metaplasia. Signalling systems needed for regeneration include the BMP and Notch signalling pathways, and perhaps also the Wnt and FGF pathways. The limb buds will regenerate completely at early stages, but not once they are fully differentiated. This provides a good opportunity to study the loss of regenerative ability using transgenic methods.     

The regeneration of newt limbs deformed in nature

Summary The regeneration of abnormal limbs from a wild newt population was examined. The abnormalities were: mirror symmetrical reduplications of digit parts, deformed wrists, or limbs with supernumerary digits. Normal regeneration resulted after amputation of the abnormal parts, regardless of the original deformity. The results suggest that the abnormalities are probably the result of local trauma to the limbs.     

The regeneration of newt limbs deformed in nature

The regeneration of abnormal limbs from a wild newt population was examined. The abnormalities were: mirror symmetrical reduplications of digit parts, deformed wrists, or limbs with supernumerary digits. Normal regeneration resulted after amputation of the abnormal parts, regardless of the original deformity. The results suggest that the abnormalities are probably the result of local trauma to the limbs.     

Cutaneous wound healing: recruiting developmental pathways for regeneration

Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/β-catenin, TGF-β, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments.     

The effect of antifibrinolytic agents on wound healing in vitro

Summary The effect of antifibrinolytic agents (antiplasminogen activators) on wound healing was studied in vitro. All these substances caused the proliferating epithelium to change direction and migrate to stratum corneum, resulting in a everted epiboly formation.     

Local action of vitamin A on amphibian limb regeneration

Summary Axolotl forearms isolated from upper arm tissue either surgically or by local irradiation regenerate excessive structures after vitamin A treatment. This demonstration excludes the possibility of regeneration being altered by enhanced cellular migration and thus indicates that vitamin A respecifies cells close to the site of amputation.     

Effect of testosterone and 17-β estradiol on limb regeneration in the newt,Notophthalmus viridescens

Summary Gonadectomy, or injections of testosterone or 17- estradiol, had no apparent effect on the rate of regeneration or histological appearance of limb regenerates in the newt,Notophthalmus viridescens. Neither promotion, nor inhibition of limb regeneration was observed.This work was supported by a grant from the National Research Council of Canada to S.R.S.     

Effect of amputation and limb regeneration on the pars distalis of the newt,Notophthalmus viridescens

Summary A study of the pituitary of the newt,Notophthalmus viridescens, during limb regeneration indicated no observable changes in histology or ultrastructure of any of the cells of the pars distalis when compared with the pars distalis of unamputated control newts.This investigation supported by a grant from the National Research Council of Canada to S.R. Scadding.     

Fibronectin in tissue regeneration: timely disassembly of the scaffold is necessary to complete the build

Tissue injury initiates extracellular matrix molecule expression, including fibronectin production by local cells and fibronectin leakage from plasma. To benefit tissue regeneration, fibronectin promotes opsonization of tissue debris, migration, proliferation, and contraction of cells involved in the healing process, as well as angiogenesis. When regeneration proceeds, the fibronectin matrix is fully degraded. However, in a diseased environment, fibronectin clearance is often disturbed, allowing structural variants to persist and contribute to disease progression and failure of regeneration. Here, we discuss first how fibronectin helps tissue regeneration, with a focus on normal cutaneous wound healing as an example of complete tissue recovery. Then, we continue to argue that, although the fibronectin matrix generated following cartilage and central nervous system white matter (myelin) injury initially benefits regeneration, fibronectin clearance is incomplete in chronic wounds (skin), osteoarthritis (cartilage), and multiple sclerosis (myelin). Fibronectin fragments or aggregates persist, which impair tissue regeneration. The similarities in fibronectin-mediated mechanisms of frustrated regeneration indicate that complete fibronectin clearance is a prerequisite for recovery in any tissue. Also, they provide common targets for developing therapeutic strategies in regenerative medicine.     

Mammalian toll-like receptors: from endogenous ligands to tissue regeneration

Following injury a complex but well-orchestrated cellular response stimulating wound healing and tissue regeneration is induced. The balance of different cytokines, growth factors and cells is important in regulating tissue reorganisation. The immune system is critically involved in this process. Toll-like receptors (TLRs) are essential to the innate immune system, recognising microbial pathogens. The recent identification of endogenous ligands of TLRs suggests that they function not only to induce defensive antimicrobial immune responses but also as a sensitive detection system to initiate tissue regeneration after injury. Here we present an overview of TLRs and their endogenous ligands, and also review the roles of TLRs in inducing tissue regeneration after injury and in maintaining homeostasis. The identification of endogenous TLR ligands and their involvement in inducing tissue regeneration will provide new options to improve tissue reorganization after injury. Received 26 April 2006; received after revision 16 June 2006; accepted 24 August 2006     

Quantitative Untersuchungen über die Proteinsyntheseaktivität von Epidermiszellen während der Extremitätenregeneration der Urodelen

Summary In the regenerating urodele limb the epidermal cells increase their volume significantly. The nucleocytoplasmic volume ratio and the protein synthesis rate obviously change in a similar manner. But in this scheme the incorporation pattern of the cells in the wound epithelium and the apical cap differs from that of all other epidermal cells by an approximately constant rate.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Fibrin stabilizing factor (F XIII) and collagen polymerization

Summary Factor XIII induces a decrease and a modification in the collagen polymerization, probably due to the formation of transamidation bonds. This property has some importance in wound healing.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Cell plasticity and mesenchymal-epithelial interactions are regarded as a hallmark of embryonic development and are not believed to occur extensively in the adult. Recently, adult mesenchymal stem cells were reported to differentiate in culture into a variety of mature cell types, including epithelial cells. Progress in stem and progenitor cell biology and recognition of the unique properties of such cells may enable intelligent bioengineering design of replacement skin which allows regeneration to occur in vivo. Ideally, a scaffold-free environment which stimulates skin stem cells in situ to initiate cell signals that result in regeneration rather than scar formation is required. Various skin progenitor cell types are considered along with the signalling cascades that they affect. We also discuss a mammalian model of scar-free regeneration. Many of these mechanisms, if fully understood, could be harnessed after injury to perfectly restore the skin.     

Proteinases in cutaneous wound healing

Cutaneous wound healing is a complex and highly coordinated process where a number of different cell types participate to renew the damaged tissue under the strict regulation of soluble and insoluble factors. One of the most versatile processes involved in wound repair is proteolysis. During cell migration, proteins of extracellular matrix are cleaved, often creating biologically active cleavage products, and proteolysis of cellular contacts leads to increased cell motility and division. Moreover, proteases activate various growth factors and other proteases in wound and regulate growth factor signaling by shedding growth factor receptors on cell surface. Normally, proteolysis is strictly controlled, and changes in protease activity are associated with alterations in wound closure and scar formation. Here, we present the current view on the role of metalloproteinases and the plasmin-plasminogen system in normal and aberrant cutaneous wound repair and discuss their role as potential therapeutic targets for chronic ulcers or fibrotic scars. Received 07 July 2008; received after revision 11 August 2008; accepted 13 August 2008     

Mise en évidence d'un système de corrélations intervenant dans la régénération des Planaires d'eau douce

Summary We show that there are correlations in regenerative fresh water planarians between all the parts of the body. When planarians are wounded in any part of the body, this mutilation will set regenerative cells in movement, which are able to travel a very long way in their migration. The extent and the speed of migration haves been shown by the method of localized X-ray irradiations.When the regenerative cells that are nearest to the wound have been killed with X-rays, regeneration occurs through the access of cells from the farther parts of the body. The nature of the stimulus is not yet known.