The human endometrium is a very dynamic tissue undergoing an extraordinary growth during pregnancy and, in a cyclic manner, during the reproductive life of each woman. Endometrial stem cells (ESCs), undifferentiated auto-renewable cells able to generate daughter cells showing a higher level of differentiation, play a fundamental role in endometrial regeneration and repair. Therefore, they have a great therapeutic potential in many diseases and research fields. However, recent data suggest that an irregular function of ESCs can contribute to the pathogenesis of endometriosis and other disorders. In addition, ESCs have also been found in human leiomyomas and malignant tumours, and could be involved in their development. In this review we analyze the enormous regenerative potential of endometrium, which is, unfortunately, not exempted from its negative effects. This coexists with the good one as two faces of the same coin and constitutes the risk behind the fundamental protective and regenerative mechanisms to defend reproduction, and therefore the miracle of life itself. Keywords: Endometrial cancer, endometrial stem cells, endometriosis, endometrium, leiomyomas, menstrual blood-derived stem cells, regenerative medicine, tissue engineering.
Background: Chondrogenic differentiation of human embryonic stem cells (hESCs) has been investigated by maintenance of 3-dimensional cultures in the presence of various exogenous growth factors added during defined stages of culture, or in cocultures with primary chondrocytes, making the cultivation process rather complex. Thus, there is a need for easier and more handy expansion and differentiation protocols. Objective: The present study is aimed to investigate the potential of hESCs for chondrogenic differentiation in simpler culture conditions. Methods: The hESCs were directly cultured for 3 weeks on feeder-free gelatin-coated plates in chondrocyte culture medium without any growth factor supplements after 6-day culture on feeder-free gelatin- coated plate with conditioned medium. Results: Immunocytochemical and gene expression analyses indicated that these human directly differentiated cells (hDDCs), which derived from the hESCs, abundantly expressed Sox9, aggrecan, and procollagen α1(II) mRNAs. Upon further passaging, the hDDCs behaved similarly to primary chondrocytes, although the aggrecan mRNA expressions were maintained at a relatively constant level throughout passaging. The procollagen α1(II) mRNAs expression was high in the beginning of the hDDC culture, but declined upon further passaging, which is typical for the primary chondrocytes. The hDDCs could be easily expanded in the monolayer culture using chondrocyte culture medium. Differentiation assays showed that the hDDCs could be differentiated towards chondrocytes, but not adipocytes or osteoblasts. Conclusion: Our data suggests that the chondrogenic gene expression could be induced in the directly differentiated hESCs without a need for chondrocyte coculture. In contrast, no osteogenic or adipogenic differentiation was observed. Keywords: Chondrogenically differentiated cells, differentiation, directly chondrogenesis, gene expression, human embryonic stem cell, monolayer culture.
Mesenchymal stem cells (MSCs) are pluripotent stem cells isolated from adipose tissue (AD-MSCs), bone marrow (BM-MSCs) and umbilical cord (UC-MSCs). Due to their ability to differentiate into multiple cell types, homing to injury sites and immunosuppressive properties have been proposed as a promising option in regenerative medicine. Studies have shown that the majority of regenerative effects of MSCs are exerted through their paracrine effects. Moreover, it has been shown that some of the regenerative functions of MSCs are mediated by exosomes, and MSC-derived exosomes play a vital role in the treatment of diseases. Since angiogenesis is a crucial process in the regeneration of damaged tissues, this review discusses the angiogenic capabilities of MSC-derived exosomes (MSC-DEs) and their mechanisms that are responsible for the control of angiogenesis in wound healing, cardiovascular diseases (CVDs) and bone defects. Keywords: Angiogenesis, cardiovascular diseases, exosome, mesenchymal stem cell, regenerative medicine, wound healing.
The analytical review is devoted to the current state of the world problem of restoring the anatomical and functional integrity of the spinal cord after trauma in experimental animal models and humans. The review includes the epidemiology and pathophysiology of spinal cord injury (SCI), the use of stem cells for local transplantation in the central nervous system, including embryonic or induced pluripotent stem cells or the precursors of neuronal and glial cells. An important place in the review is devoted to the use of neuronal trophic factors in the concept of reconstructive therapy of spinal cord injuries. The authors singled out the experimental and clinical directions of the restoration of the conduction pathways and functions of the spinal cord when it is damaged placing emphasis on the combined use of cellular, neuronal trophic ingredients based on the most modern biodegradable implants with the properties of target molecule system delivery. Considering the fact that obtaining reprogrammed neuronal cells from IPSCh take a long time with a small output of specialized cell mass, the authors of the review give examples of modern promising technologies for solving this problem. The analysis of biodegradable matrices for cell transplantation into the area of spinal cord injury focuses on the role of chitosan biopolymer as a promising material for regenerative medicine, in particular for the elimination of spinal cord injury. The authors' own results point to the successful experimental use of cellular collagen-chitosan matrices in the reconstruction of the spinal cord during its full transection. A separate section is devoted to the role of angiogenesis factors in the restoration of spinal cord functions and the contribution of chitosan polymers in the formation of therapeutic angiogenesis in spinal cord injury. The authors of the article draw attention to recommendations for basic and clinical trials of cellular products, biological surveillance, transparency of manipulation and ethics, presented by the International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) and the International Society for Stem Cell Research (ISSCR). Keywords: Biopolymers, cellular reconstruction technologies, collagen-chitosan scaffold, experiment and clinic, neurotrophic support, prospects, recovery strategy, spinal cord injury.
Background: Leishmania parasites causative agents of leishmaniasis are aerotolerant or microaerophilic and consume oxygen to some extent. Leishmania parasites produce hydrogen peroxide as a metabolism product in certain circumstances and are naturally exposed to the toxin metabolites such as Reactive Oxygen Species generated by macrophages. To stand oxidative stress, trypanosomatids evolved a unique dithiol trypanothione pathway which consists of a cascade of low molecular weight thiol specific oxidoreductases acting in the order of trypanothione reductase, trypanothione, tryparedoxin, and tryparedoxin peroxidase to detoxify peroxides. Tryparedoxin peroxidases belong to a widespread family of peroxiredoxins. Keywords: Hydrogen peroxide, kinetoplastida, Leishmania, peroxiredoxin, ROS, tryparedoxin peroxidase.
Acute and chronic kidney diseases represent an emerging problem in management and costs of healthcare. Understanding the mechanisms responsible for injury and repair is the mainstay to a more precise classification and staging thus envisioning potential strategies of intervention. Experimental models of acute kidney disease and chronic kidney disease are important even if necessarily artefactual to having a deep insight into the mechanisms of acute lesions and functional deterioration. The evidence that even a single episode of acute kidney disease predisposes the kidney to initiate a complex series of events leading to scarring and reduction of functional parenchyma emphasizes the need to prevent acute kidney disease or to reduce its impact in the later development of chronic kidney disease. In the past years, innovative cell therapies with stem cells have been proposed and tested in pre-clinical development and in pilot clinical studies, leading to the strong hope that these novel approaches might be of relevance. However, not all these studies have led to a unanimous agreement mainly due to lack of standardization, batch-to-batch variability, lack of potency tests, and difficulty in patient stratification. More recently, extracellular vesicles, nanoparticles released physiologically from all cells, and capable of transferring genetic information to target cells, have attracted major interest in regenerative medicine. In this review, we intend to describe the main mechanisms of acute kidney disease and chronic kidney disease, the experimental models that may allow insight into the mechanisms and the potential therapeutic targets using stem cells and their derived extracellular vesicles. A compilation of the main patents relative to stem cells and extracellular vesicles in acute kidney disease and chronic kidney disease will follow. Keywords: Exosomes, experimental models, extracellular vesiscles, microvesicles, renal injury, stem cells.
Background: In recent years, tissue engineering (TE) and regenerative medicine (RM) are rapidly evolving fields. TE and RM are part of the biomedical field, and both are emergent research areas with a high impact on medical issues. The development of new types of novel, effective and highly reliable engineering constructs is essential to tackle many human health-related diseases. To this end, materials science technology offers an excellent engineering exploitability. Keywords: Biomaterials, bone tissue engineering, heart tissue engineering, novel constructs, organs, regeneration, skin tissue engineering, tissue engineering.
Induction of donor-specific immunological tolerance in order to eliminate the lifelong systemic immunosuppressive therapy and their deleterious side effects as well as to prevent graft loss due to acute or chronic rejection or drug toxicity has been considered the "Holy Grail" of transplantation. The only effective approach of inducing tolerance is combined organ (e.g. kidney) and donor bone marrow transplantation. The hallmark of this protocol is establishment of chimerism and preferentially mixed chimerism using non-meyloablative condition which reduces the risk of GVHD, as well as its feasibility and safety for tolerance induction even in HLA-mismatched kidney graft recipients. The focus of this review is to discuss the last findings of clinical trials mainly from three medical centers as pioneers for designing and implementing tolerance protocols using chimerism-based approaches. Finally, the merits and drawbacks of these protocols are discussed with regard to the feasibility of such protocols for deceased donor grafts and more widespread application in clinical transplantation. Keywords: Allograft, chimerism, kidney, stem cells, tolerance, transplantation.
Background: Platelet rich plasma is one of the simplest regenerative medicine method used to deliver growth factors and other substances at the desired areas in higher concentrations. PRP is proved to help in tissue regeneration and augments tissue healing. It is being used in variety of conditions in many surgical and medical conditions. There are multiple commercially available preparation kits which vary in terms of different aspects. However, the vast variations in the clinical settings lack any standardization in preparation, composition and delivery methods. The presence of different cells also influences the outcome of the clinical studies. Keywords: Alopaecia, growth factors, hair restoration, platelet rich plasma, regenerative medicine, wound healing.
Background: Human microRNAs (miRs) that have been evaluated toward medical application are largely the early-introduced sequences numbered below 1000, with GC content close to Drosophila melanogaster fruitfly, but rather below current averages for human miRs. The research bias toward low database numbers and low GC content is found for all sectors of human miRs. Keywords: AU content, GC content, microRNA categories, nucleotide iterons, polynucleotide mRNA interaction, RNA hydrogen bonding.
