Interrelation of immunity and tissue repair or regeneration

Although tremendous progress has been achieved in understanding the molecular basis of tissue repair and regeneration in diverse model organisms, the tendency of mammals for imperfect healing and scarring rather than regeneration remains unexplained. Moreover, conditions of impaired wound healing, e.g. non-healing skin ulcers associated with diabetes mellitus or vascular disease, as well as excessive scarring, represent major clinical and socio-economical problems. The development of innovative strategies to improve tissue repair and regeneration is therefore an important task that requires a more thorough understanding of the underlying molecular and cellular mechanisms.There is substantial evidence in different model organisms that the immune system is of primary importance in determining the quality of the repair response, including the extent of scarring, and the restoration of organ structure and function. Findings in diverse species support a correlation between the loss of regeneration capacity and maturation of immune competence. However, in recent years, there is increasing evidence on conditions where the immune response promotes repair and ensures local tissue protection. Hence, the relationship between repair and the immune response is complex and there is evidence for both negative and positive roles.We present an overview on recent evidence that highlights the immune system to be key to efficient repair or its failure. First, we summarize studies in different model systems that reveal both promoting and impeding roles of the immune system on the regeneration and repair capacity. This part is followed by a delineation of diverse inflammatory cell types, selected peptide growth factors and their receptors as well as signaling pathways controlling inflammation during tissue repair. Finally, we report on new mechanistic insights on how these inflammatory pathways impair healing under pathological conditions and discuss therapeutic implications.     

Histogenesis of skeletogenic tissue in bone regeneration during distraction

Light and electron microscopy were employed to study the histogenesis of the skeletogenous tissue during stable distraction osteosynthesis according to G. A. Ilizarov. Osteosynthesis proceeded on the basis of the invariably existing fibrillar connective tissue growth plate situated in the medium part of the distraction regenerate. Osteogenesis was continuously accompanied by angiogenesis. Preservation of the connective tissue plate is accounted for by the stimulating influence of distraction on fibrillogenesis. The authors suggest the common character of the histogenesis of the vascular and bone tissues in the connective tissue blastema of the interfragmental distraction regenerate.     

Healing of bone defects by guided tissue regeneration

In this study we describe a principle for the accomplishment of bone regeneration based on the hypothesis that different cellular components in the tissue have varying rates of migration into a wound area during healing. By a mechanical hindrance, using a membrane technique, fibroblasts and other soft connective-tissue cells are prevented from entering the bone defect so that the presumably slower-migrating cells with osteogenic potential are allowed to repopulate the defect. Defects of standard size were created bilaterally through the mandibular angles of rats. On one side of the jaw the defect was covered with Teflon membranes, whereas the defect on the other side served as control. Histologic analysis after healing demonstrated that on the test (membrane) side, half the number of animals showed complete bone healing after 3 weeks and all animals showed complete healing after 6 weeks. Little or no sign of healing was evident on the control side even after an observation period of 22 weeks.     

The role of recipient T cells in mesenchymal stem cell-based tissue regeneration

Significant progress has been made in stem cell biology, regenerative medicine, and stem cell-based tissue engineering. Such scientific strides highlight the potential of replacing or repairing damaged tissues in congenital abnormalities, diseases, or injuries, as well as constructing functional tissue or organs in vivo. Since mesenchymal stem cells (MSCs) are capable of differentiating into bone-forming cells, they constitute an appropriate cell source to repair damaged bone tissues. In addition, the immunoregulatory property of MSCs provides a foundation for their use in treating a variety of autoimmune diseases. However, the interaction between MSCs and immune cells in cell-based tissue regeneration is largely unknown. In this review, we will discuss the current understanding of MSC-based tissue regeneration, emphasizing the role of the immune microenvironment in bone regeneration.     

Biodegradable bone regeneration synthetic scaffolds: in tissue engineering

A growing array of synthetic bone regeneration scaffolds has been used or investigated over the last century. These scaffolds aim to provide a three dimensional substrate for bone cells to populate on and function appropriately. To serve this function, these scaffolds should be biocompatible and biodegradable at a rate commensurate with bone remodelling. Their mechanical properties should also be similar to those of the bone regeneration site. In this review, the main families of synthetic bone scaffolds were taxonomised and expounded. The main focus of this paper will be on the basic sciences principles and properties of clinical available as well as experimental synthetic bone scaffolds. Special emphasis was put on scaffolds developed over the last ten years.     

The role of the myoblasts and connective tissue in the regeneration of the limbs in amphibians

A possibility of tissue metaplasia (transformation of one cell type into another) during limb regeneration in lower vertebrates has been a matter of vivid arguments over the last decades. These discussions are rather irreconcilable in character mainly due to the lack of reliable cell markers which permit to follow all the stages of cell transformation during metaplasia. The final conclusions can be made only if any artifacts of cell labelling are excluded. Latest findings obtained using nuclear and cytoplasmic markers are presented which suggest that many data interpreted previously as a convincing proof of metaplasia may be a consequence of the involvement of nondifferentiated cells in regeneration. Molecular biological approaches are believed to be most promising for the solution of disputable problems of tissue metaplasia. However, recent findings about actin gene hypomethylation are insufficient for any final conclusions about the possibility of metaplasia during limb regeneration. The answer to many unsolved questions of developmental biology can be made only when combined use is made of modern methods of cell and molecular biology.     

Delivery of bone morphogenetic proteins for orthopedic tissue regeneration

Carriers for bone morphogenetic proteins (BMPs) are used to increase retention of these factors at orthopedic treatment sites for a sufficient period of time to allow regenerative tissue forming cells to migrate to the area of injury and to proliferate and differentiate. Carriers can also serve as a matrix for cell infiltration while maintaining the volume in which repair tissue can form. Carriers have to be biocompatible and are often required to be bioresorbable. Carriers also have to be easily, and cost-effectively, manufactured for large-scale production, conveniently sterilized and have appropriate storage requirements and stability. All of these processes have to be approvable by regulatory agencies. The four major categories of BMP carrier materials include natural polymers, inorganic materials, synthetic polymers, composites of these materials. Autograft or allograft carriers have also used. Carrier configurations range from simple depot delivery systems to more complex systems mimicking the extracellular matrix structure and function. Bone regenerative carriers include depot delivery systems for fracture repair, three-dimensional polymer or ceramic composites for segmental repairs and spine fusion and metal or metal/ceramic composites for augmenting implant integration. Tendon/ligament regenerative carriers range from depot delivery systems to three-dimensional carriers that are either randomly oriented or linearly oriented to improve regenerative tissue alignment. Cartilage regenerative systems generally require three-dimensional matrices and often incorporate cells in addition to factors to augment the repair. Alternative BMP delivery systems include viral vectors, genetically altered cells, conjugated factors and small molecules.     

The role of multipotent marrow stromal cells (MSCs) in tissue regeneration

An extensive body of preclinical and clinical data has shown that administration of adult multipotent marrow stromal cells (MSCs) effectively ameliorates experimental and clinical conditions of many different organ systems. Differentiation into organ parenchymal cells, however, is very rare, and the main mechanism for organ protection and regeneration from different types of injury is the exertion of paracrine effects and stimulation of tissue repair. A large number of clinical trials have been conducted and are ongoing to investigate the safety and efficacy of MSCs in different organs after various types of organ injury. This article intends to give a brief overview about current applications of MSCs and mechanisms involved in organ protection and regeneration.     

The role of multipotent marrow stromal cells (MSCs) in tissue regeneration

An extensive body of preclinical and clinical data has shown that administration of adult multipotent marrow stromal cells (MSCs) effectively ameliorates experimental and clinical conditions of many different organ systems. Differentiation into organ parenchymal cells, however, is very rare, and the main mechanism for organ protection and regeneration from different types of injury is the exertion of paracrine effects and stimulation of tissue repair. A large number of clinical trials have been conducted and are ongoing to investigate the safety and efficacy of MSCs in different organs after various types of organ injury. This article intends to give a brief overview about current applications of MSCs and mechanisms involved in organ protection and regeneration.     

The role of HIF in immunity

Oxygen is an essential nutrient for eukaryotic life and in complex organisms a finely tuned system, based on Hypoxia Inducible Factor (HIF), has evolved to control the cellular, local and organism-wide responses to its availability. Cells of the immune system must function in a variety of local environments and it is now clear that oxygen availability is an important signal for the cells involved in immune defence. This review summarises the mechanisms by which activation of the HIF pathway influences, and is influenced by, both immune activation state and oxygen tension. It is likely that understanding how oxygen tension modulates immune function will provide insights into disease pathogenesis, and may offer new opportunities for treatment.     

Microcomputed tomography-based structural analysis of various bone tissue regeneration models

Microcomputed tomography (microCT) analysis is a powerful tool for the evaluation of bone tissue because it provides access to the 3D microarchitecture of the bone. It is invaluable for regenerative medicine as it provides the researcher with the opportunity to explore the skeletal system both in vivo and ex vivo. The quantitative assessment of macrostructural characteristics and microstructural features may improve our ability to estimate the quality of newly formed bone. We have developed a unique procedure for analyzing data from microCT scans to evaluate bone structure and repair. This protocol describes the procedures for microCT analysis of three main types of mouse bone regeneration models (ectopic administration of bone-forming mesenchymal stem cells, and administration of cells after both long bone defects and cranial segmental bone defects) that can be easily adapted for a variety of other models. Precise protocols are crucial because the system is extremely user sensitive and results can be easily biased if standardized methods are not applied. The suggested protocol takes 1.5-3.5 h per sample, depending on bone tissue sample size, the type of equipment used, variables of the scanning protocol and the operator's experience.     

The role of animals in the epidemiology of the mycoses

The role that animals play in the epidemiology of human mycoses is discussed here. It can be divided as follows:Animals as vectors of mycoses — This role is especially important as far as dermatophytozoonoses are concerned, these being of both the urban type, mainly due to Microsporum canis, and of the rural type, mainly due to Trichophyton verrucosum. These dermatophytozoonoses are emerging problems in present, modern pathology, especially in urban areas. These conditions may also be responsible for important occupational diseases for livestock, rabbit and laboratory attendants. Both domestic animals and wildlife are often asymptomatic carriers.Animal substrates as growths factor for pathogenic fungi — The fact that bird or bat feces may contain factors that favour the growth of some fungous organisms in the environment has long been recognized. It is established fact that soil animalization (i.e., the addition of such debris as hair, skin scales, droppings and other organic matters) create an environmental medium suitable for the growth of geophilic fungi such as Histoplasma capsulatum, Cryptococcus neoformans and M. gypseum.Possible role of animals in the recycling of fungi from foodstuffs and environment — The possible role of animals in determining human pathology has become an emerging problem for which new data are accumulating both on pathogenic fungi and mycotoxins.The use of animals in monitoring mycoses — Animals may reveal the presence of a pathogen in a given area. This phenomenon has been exploited to monitor the natural occurrence of various mycoses (e.g., coccidioidomycosis, histoplasmosis, dermatomycoses) in different regions. The use of sentinel animals (i.e., the introduction of susceptible animals in certain environments to detect the presence of a pathogen) has not been duly exploited.     

T-system in muscles of microdriles

Ribbon-like longitudinal fibers of the body wall of enchytraeids and lumbriculids are grouped in fuctional units. The organization of subsarcolemmal cisternae, membrane foldings and extracellular spaces between fibers is described. The data seem to indicate that the spaces between fibers within each functional unit are interpretable as T-tubules of a cross-striated fiber.     

The role of G-CSF in adaptive immunity

Granulocyte colony-stimulating factor (G-CSF) is a pleiotropic cytokine playing a major role as regulator of hematopoiesis and innate immune responses. There is growing evidence that G-CSF also exerts profound immunoregulatory effects in adaptive immunity. G-CSF mediates anti-inflammatory reactions accompanied by TH2 cell differentiation and promotes tolerogeneic cell populations at both poles of APC/T cell interaction. These recent findings have highlighted the novel impact of G-CSF in transplantation tolerance and autoimmunity. G-CSF represents a powerful and promising cytokine to promote T cell tolerance in pathological conditions associated with a TH1/TH2 imbalance.     

The role of IgM in paratyphoid immunity

The authors analyze the results of studies on the effect produced by the immunization of calves with paratyphoid vaccine on the production of agglutinins, changes in the blood serum immunoglobulin levels, and the specificity of IgM to Salmonella dublin and Salmonella typhimurium antigens. The highest level of agglutinins to paratyphoid antigens in the blood sera of the immunized calves was registered on days 14-21 after immunization, changes in the levels of different immunoglobulin classes being insignificant. The agglutination test and the enzyme immunoassay have revealed that antibodies to S. dublin anb S. typhimurium antigens belong to IgM.     

The role of G-proteins in plant immunity

Heterotrimeric G-proteins play an important regulatory role in multiple physiological processes, including the plant immune response, and substantial progress has been made in elucidating the G-protein-mediated defense-signaling network. This mini-review discusses the importance of G-proteins in plant immunity. We also provide an overview of how G-proteins affect plant cell death and stomatal movement. Our recent studies demonstrated that G-proteins are involved in signal transduction and induction of stomatal closure and defense responses. We also discuss future directions for G-protein signaling studies involving plant immunity.