Cross-talk between wound signalling pathways determines local versus systemic gene expression in Arabidopsis thaliana

Plants react to mechanical damage by activating a set of genes, the products of which are thought to serve defensive functions. In solanaceous plants, cell wall-derived oligosaccharides and the plant hormones jasmonic acid and ethylene participate in the signalling network for wound-induced expression of proteinase inhibitors and other defence-related genes, both in the locally damaged and in the systemic non-damaged leaves. Here we show that in Arabidopsis thaliana, these signalling components interact in novel ways to activate distinct responses. In damaged tissues, oligosaccharides induce the expression of a specific set of wound-responsive genes while repressing jasmonic acid-responsive genes that are activated in the systemic tissues. The oligosaccharide-mediated repression of the jasmonic acid-dependent signalling pathway is exerted through the production and perception of ethylene in the locally damaged tissue. This cross-talk between separate wound signalling pathways thus allows the set up of different responses in the damaged and the systemic tissues of plants reacting to injury.     

Mechanism of the occurrence of postinjection abscesses

The decisive factor in the appearance of postinfection abscesses is the presence of damaged tissues, open to the penetration of microorganisms not only by the exogenic or endogenic route, but also by the so-called exoendogenic route, when they penetrate the body from the air via the upper respiratory ways and further into the blood and damaged tissues.     

Regeneration Around Wounds and the Control of Vascular Differentiation

The question which was the basis of this work was whether (a)vascular regeneration around wounds includes a replacement ofdamaged tissues or (b) only new vascular strands, which arenormally formed from the cambium, are diverted around wounds.It was found that in Coleus and Cucumis no connections are formedto damaged sieve tubes and vessels, so that their continuityaround wounds is not restored. Pisum plants were wounded underconditions in which growth could not be influenced and the areaof the xylem in cross-section was measured 1 month later. Thewounds, which damaged the vascular tissues, significantly increasedvascular differentiation, indicating the replacement of a longnon-functional region of damaged tissues. The results indicatethat in the intact plant vascular differentiation is controllednot only by stimuli from the leaves but also by the capacityof the mature vascular system to transport these stimuli.     

凋亡细胞的清除及组织稳态维持的研究进展

机体在组织器官受到损伤时,细胞凋亡和机体对凋亡细胞的清除在组织再生中有着密不可分的联系,其背后促进受损组织器官再生的机制一直是研究热点所在。近期研究发现,巨噬细胞在清除凋亡细胞,维持机体稳态以及促进组织器官修复再生中起到了重要作用。本文主要从凋亡的信号通路、巨噬细胞的极化特点以及凋亡细胞与巨噬细胞的相互作用这3个方面对近期研究进行综述。     

Stem cells and growth factor delivery systems for cardiovascular disease

Coronary (CAD) and peripheral (PAD) artery diseases are major causes of morbidity and mortality, and millions of CAD and PAD patients are treated by various medications, bypass surgery or angioplasty around the world. Such patients might benefit from novel stem cells and tissue engineering strategies aimed at accelerating natural processes of postnatal collateral vessel formation and repairing damaged tissues. By combining three fundamental “tools”, namely stem cells, biomaterials and growth factors (GFs), such strategies may enhance the efficacy of cell therapy in several ways: (a) by supplying exogenous stem cells or GFs that stimulate resident cardiac stem cell (CSC) migration, engraftment and commitment to cardiomyocytes, and that induce and modulate arterial response to ischemia; (b) by supporting the maintenance of GFs and transplanted stem cells in the damaged tissues through the use of biocompatible and biodegradable polymers for a period of time sufficient to allow histological and anatomical restoration of the damaged tissue. This review will discuss the potential of combining stem cells and new delivery systems for growth factors, such as vehicle-based delivery strategies or cell-based gene therapy, to facilitate regeneration of ischemic tissues. These approaches would promote the ability of resident CSCs or of exogenous multipotent stem cells such as adipose tissue-derived mesenchymal stem cells (AT-MSCs) to induce the healing of damaged tissue, by recruiting and directing these cells into the damage area and by improving angiogenesis and reperfusion of ischemic tissues.     

Growth control: p53, the guardian angel of compensatory proliferation

Compensatory growth, or regeneration, is used to replace damaged tissue during animal development. Recent work has revealed a new role for Drosophila p53 in the compensatory proliferation of cells that are needed to repair damaged tissues, a role that requires the non-apoptotic function of the caspase protease Dronc.     

Accumulation of defective mitochondria through delayed degradation of damaged organelles and its possible role in the ageing of post-mitotic and dividing cells

The mitochondrial theory of ageing proposes that an accumulation of defective mitochondria is a major contributor to the cellular deterioration that underlies the ageing process. The plausibility of the mitochondrial theory depends critically upon the population dynamics of intact and mutant mitochondria in different cell types. Earlier work suggested that mutant mitochondria might have a replication advantage but failed to account for the fact that mutants accumulate faster in post-mitotic than in dividing cells. We describe a new mathematical model that allows for damaged mitochondria to replicate more slowly, which accommodates experimental evidence of impaired energy generation and a reduced proton gradient in defective mitochondria. However, this is compensated for by a slower degradation rate of damaged mitochondria than intact ones, as suggested by de Grey (1997), which gives damaged mitochondria a selective advantage and leads to a clonal expansion of damaged mitochondria. This theoretical result is important because it agrees with evidence that, during ageing, single muscle fibres are taken over by one or only a few types of mtDNA mutants. The model also shows that cell division can rejuvenate and stabilize the mitochondrial population, consistent with data that post-mitotic tissues accumulate mitochondrial damage faster than mitotically active tissues.     

Progenitor cells in vascular repair

PURPOSE OF REVIEW: A common characteristic of all types of vascular disease is endothelial dysfunction/damage followed by an inflammatory response. Although mature endothelial cells can proliferate and replace damaged cells in the vessel wall, recent findings indicate an impact of stem and progenitor cells in repair process. This review aims to briefly summarize the recent findings in stem/progenitor cell research relating to vascular diseases, focusing on the role of stem/progenitor cells in vascular repair. RECENT FINDINGS: It has been demonstrated that endothelial progenitor cells present in the blood have an ability to repair damaged arterial-wall endothelium. These cells may be derived from a variety of sources, including bone marrow, spleen, liver, fat tissues and the adventitia of the arterial wall. In response to cytokine released from damaged vessel wall and adhered platelets, circulating progenitor cells home in on the damaged areas. It was also reported that the adhered progenitor cells can engraft into endothelium and may differentiate into mature endothelial cells. SUMMARY: Vascular progenitor cells derived from different tissues have an ability to repair damaged vessel, in which the local microenvironment of the progenitors plays a crucial role in orchestrating cell homing and differentiation.     

Hepatic Damage Influences the Decay of Nitroxide Radicals in Mice—An In Vivo ESR Study

To determine the role of the liver in the elimination of free radicals from the body, the clearance rate (K) of nitroxide radicals (Tempol) at the hepatic domain was compared with that at the pelvic domain of live mice, using L-band ESR spectroscopy. The reduction of Ternpol in biopsy specimens (liver tissue and femoral muscle) and blood obtained from Tempol-treated mice was also monitored using X-band ESR spectroscopy. Results indicated that the reduction of nitroxide radicals was delayed in both the liver and peripheral tissues when the liver was damaged. The decrease in both blood supply and reductants in the damaged liver might be involved in delaying the reduction in the whole body, because the liver can reduce the radicals supplied via the blood from the peripheral tissues, and the reductants such as reduced glutathione in the peripheral tissues are supplied from the liver.     

Interplay of cell proliferation and cell death in Drosophila tissue regeneration

Regeneration is a fascinating process that allows some organisms to reconstruct damaged tissues. In addition to the classical regeneration model of the Drosophila larval imaginal discs, the genetically induced tissue ablation model has promoted the understanding of molecular mechanisms underlying cell death, proliferation, and remodeling for tissue regeneration. Recent studies have also revealed that tissue injury responses occur not only locally but also systemically, even in the uninjured region. Genetic studies in Drosophila have demonstrated the dynamic role of the cell death‐induced tissue response in the reconstruction of damaged tissues.     

Regenerative biology and medicine

The replacement of damaged tissues and organs with tissue and organ transplants or bionic implants has serious drawbacks. There is now emerging a new approach to tissue and organ replacement, regenerative biology and medicine. Regenerative biology seeks to understand the cellular and molecular differences between regenerating and non-regenerating tissues. Regenerative medicine seeks to apply this understanding to restore tissue structure and function in damaged, non-regenerating tissues. Regeneration is accomplished by three mechanisms, each of which uses or produces a different kind of regeneration-competent cell. Compensatory hyperplasia is regeneration by the proliferation of cells which maintain all or most of their differentiated functions (e.g., liver). The urodele amphibians regenerate a variety of tissues by the dedifferentiation of mature cells to produce progenitor cells capable of division. Many tissues contain reserve stem or progenitor cells that are activated by injury to restore the tissue while simultaneously renewing themselves. All regeneration-competent cells have two features in common. First, they are not terminally differentiated and can re-enter the cell cycle in response to signals in the injury environment. Second, their activation is invariably accompanied by the dissolution of the extracellular matrix (ECM) surrounding the cells, suggesting that the ECM is an important regulator of their state of differentiation. Regenerative medicine uses three approaches. First is the transplantation of cells into the damaged area. Second is the construction of bioartificial tissues by seeding cells into a biodegradable scaffold where they produce a normal matrix. Third is the use of a biomaterial scaffold or drug delivery system to stimulate regeneration in vivo from regeneration-competent cells. There is substantial evidence that non-regenerating mammalian tissues harbor regeneration-competent cells that are forced into a pathway of scar tissue formation. Regeneration can be induced if the factors leading to scar formation are inhibited and the appropriate signaling environment is supplied. An overview of regenerative mechanisms, approaches of regenerative medicine, research directions, and research issues will be given.     

Current and novel polymeric biomaterials for neural tissue engineering

The nervous system is a crucial component of the body and damages to this system, either by of injury or disease, can result in serious or potentially lethal consequences. Restoring the damaged nervous system is a great challenge due to the complex physiology system and limited regenerative capacity.Polymers, either synthetic or natural in origin, have been extensively evaluated as a solution for restoring functions in damaged neural tissues. Polymers offer a wide range of versatility, in particular regarding shape and mechanical characteristics, and their biocompatibility is unmatched by other biomaterials, such as metals and ceramics. Several studies have shown that polymers can be shaped into suitable support structures, including nerve conduits, scaffolds, and electrospun matrices, capable of improving the regeneration of damaged neural tissues. In general, natural polymers offer the advantage of better biocompatibility and bioactivity, while synthetic or non-natural polymers have better mechanical properties and structural stability. Often, combinations of the two allow for the development of polymeric conduits able to mimic the native physiological environment of healthy neural tissues and, consequently, regulate cell behaviour and support the regeneration of injured nervous tissues.Currently, most of neural tissue engineering applications are in pre-clinical study, in particular for use in the central nervous system, however collagen polymer conduits aimed at regeneration of peripheral nerves have already been successfully tested in clinical trials.This review highlights different types of natural and synthetic polymers used in neural tissue engineering and their advantages and disadvantages for neural regeneration.     

Differentiation Potential of Mesenchymal Stem Cells and Stimulation of Nerve Regeneration

Mesenchymal stem cells (MSCs) are widely used in experimental research on cell therapy intended for the stimulation of repair processes in damaged tissues and organs. The present review summarizes the results of studies devoted to the possible directions of MSC differentiation after the transplantation of these cells into damaged nerves or special engineered structures of biological and artificial biodegradable materials that join the ends of a damaged nerve (nerve conduits). Data on exogenous MSC differentiation into Schwann cells, pericytes, smooth muscle cells, endotheliocytes, and other cell types are presented. Methods for preliminary MSC differentiation in vitro and examples of beneficial effects of these cells transplanted into damaged conductive nerves on nerve regeneration are given. The fate of exogenous MSCs placed into an unnatural biological niche remains poorly characterized and requires further studies, as emphasized in the review.     

Ultrastructure and energy-dispersive x-ray microanalysis of cartilage after rapid freezing, low temperature freeze drying, and embedding in Spurr's resin

In order to undertake meaningful high-resolution x-ray microanalysis of tissues, methods should be used that minimize the introduction of artefacts produced by loss or translocation of ions. The most ideal method is rapid freezing but the subsequent sectioning of frozen tissues is technically difficult. An alternative method is to freeze dry the tissues at a low temperature, and then embed them in resin. This facilitates the rapid production of reproducible thin sections. With freeze-dried, embedded hypertrophic cartilage, the morphology was similar to that seen using aqueous fixatives even when no additional electron density is introduced by the use of osmium vapor. Energy-dispersive analysis of specific areas show that little or no loss or migration of ions occurs from structures such as mitochondria. Mitochondrial granules consisting of calcium and phosphorus precipitates were not observed except where the cells were damaged as a result of the freezing process. This may suggest that these granules only appear when tissue is damaged because of inadequate preservation.     

One-dimensional viscoelastic behavior of fibroblast populated collagen matrices

Bio-artificial tissues are being developed as replacements for damaged biologic tissues. Their mechanical properties are critical for load bearing applications. Current testing protocols for bio-artificial tissues vary widely and often do not consider viscoelasticity. Uniaxial stretch tests were performed on fibroblast populated collagen matrices (FPCMs) to determine the influence of specific test protocols on the mechanical behavior. The peak force, hysteresis and shape of the force-stretch curve are affected by the stretch rate, rest period, stretch amplitude and the number and magnitude of preconditioning cycles.     

Alginate Hydrogels as Scaffolds and Delivery Systems to Repair the Damaged Spinal Cord

Alginate (ALG) is a lineal hydrophilic polysaccharide present in brown algae cell walls, which turns into a gel state when hydrated. Gelation readily produces a series of three dimensional (3D) architectures like fibers, capillaries, and microspheres, used as biosensors and bio‐actuators in a plethora of biomedical applications like drug delivery and wound healing. Hydrogels have made a great impact on regenerative medicine and tissue engineering because they are able to mimic the mechanical properties of natural tissues due to their high water content. Recent advances in neurosciences have led to promising strategies for repairing and/or regenerating the damaged nervous system. Spinal cord injury (SCI) is particularly challenging, owing to its devastating medical, human, and social consequences. Although effective therapies to repair the damaged spinal cord (SC) are still lacking, multiple pharmacological, genetic, and cell‐based therapies are currently under study. In this framework, ALG hydrogels constitute a source of potential tools for the development of implants capable of promoting axonal growth and/or delivering cells or drugs at specific damaged sites, which may result in therapeutic strategies for SCI. In this mini‐review, the current state of the art of ALG applications in neural tissues for repairing the damaged spinal cord is discussed.     

Induction of ethylene synthesis and lipid peroxidation in damaged or TMV-infected tobacco leaf tissues by light

The effect of light on ethylene and ethane production in damaged leaf tissues was investigated. When whole leaves of tobacco cv. Samsun NN were damaged with liquid nitrogen, the ethylene formation was the highest, if 100?% of leaves were injured and were kept in the light, the lowest when leaves after 100?% injury were kept in darkness. Ethane production (lipid peroxidation) could be detected only in damaged, but not in control leaves, and was much higher in light than in darkness. In addition, there was a strong degradation of chlorophyll of damaged leaves kept in light. In light aminoethoxy-vinylglycine (AVG) inhibited ethylene formation in control, non-damaged whole leaves effectively, but in leaves with 100?% damage the inhibitory effect was much weaker and similar to the effect of propyl gallate (PG), a free radical scavenger. Both AVG and PG treatments decreased ethylene formation by control leaf discs and discs with 100?% damage. Ethane production was significantly inhibited by PG and slightly by AVG in the case of 100?% damage. Tiron, another free radical scavenger gave similar results on leaf discs as PG did. Paraquat (methylviologen, Pq), as a photosynthesis inhibiting and reactive oxygen species (ROS) producing herbicide produced a large amount of ethylene and ethane in light but very small amount in darkness. In accordance, tobacco mosaic virus (TMV) infection on the necrotic host resulted in significantly larger amount of ethylene and ethane formation in light than in darkness. We conclude that ethylene and ethane production of damaged plant tissues is strongly induced by light and ROS that are involved in this induction.     

Nuclear reprogramming: a key to stem cell function in regenerative medicine

The goal of regenerative medicine is to restore form and function to damaged tissues. One potential therapeutic approach involves the use of autologous cells derived from the bone marrow (bone marrow-derived cells, BMDCs). Advances in nuclear transplantation, experimental heterokaryon formation and the observed plasticity of gene expression and phenotype reported in multiple phyla provide evidence for nuclear plasticity. Recent observations have extended these findings to show that endogenous cells within the bone marrow have the capacity to incorporate into defective tissues and be reprogrammed. Irrespective of the mechanism, the potential for new gene expression patterns by BMDCs in recipient tissues holds promise for developing cellular therapies for both proliferative and post-mitotic tissues.     

Regulation of myofibroblast activities: Calcium pulls some strings behind the scene

Myofibroblast-induced remodeling of collagenous extracellular matrix is a key component of our body's strategy to rapidly and efficiently repair damaged tissues; thus myofibroblast activity is considered crucial in assuring the mechanical integrity of vital organs and tissues after injury. Typical examples of beneficial myofibroblast activities are scarring after myocardial infarct and repair of damaged connective tissues including dermis, tendon, bone, and cartilage. However, deregulation of myofibroblast contraction causes the tissue deformities that characterize hypertrophic scars as well as organ fibrosis that ultimately leads to heart, lung, liver and kidney failure. The phenotypic features of the myofibroblast, within a spectrum going from the fibroblast to the smooth muscle cell, raise the question as to whether it regulates contraction in a fibroblast- or muscle-like fashion. In this review, we attempt to elucidate this point with a particular focus on the role of calcium signaling. We suggest that calcium plays a central role in myofibroblast biological activity not only in regulating contraction but also in mediating intracellular and extracellular mechanical signals, structurally organizing the contractile actin-myosin cytoskeleton, and establishing lines of intercellular communication.     

Multiple growth factor delivery for skin tissue engineering applications

Administration of exogenous growth factors (GFs) to a damaged site has been investigated for skin tissue regeneration. Among the many types of GFs and cytokines, epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and hepatocyte growth factor could be specifically used for stimulating molecules in wound healing as well as for recovery of damaged skin tissues. It is speculated that delivered GFs could stimulate various cellular functions, including proliferation, migration, deposition of extracellular matrix molecules, and remodeling of collagen synthesis. Although the physiological wound healing process is complex, engineering strategies for proper delivery of multiple therapeutic GFs could enhance the quality and quantity of regenerated skin tissues. As compared to single delivery of a GF, recent studies have proven that any combination of multiple GFs and/or therapeutic chemical factors synergistically facilitates the regeneration of damaged skin tissues. In order to maximize the stability, bioactivity, intrinsic therapeutic functionality, and efficiency of internal delivery of cargo GFs, it is essential to utilize tissueengineered biomaterials and related composites as implantable platforms. Successful fabrication and development of skin tissue engineering applications as well as subsequent surgical implantation of these platforms might provide clinical treatment for superior skin regeneration. Therefore, the present review summarizes the biological functions, related signaling mechanisms, and recent developments of tissue engineering applications for multiple GF delivery.