Current Regenerative Medicine (Discontinued) - Volume 6, Issue 1, 2016

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.

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.

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. Background: Leishmania parasites causative agents of leishmaniasis are aerotolerant or Objective: It is necessary to review tryparedoxin peroxidase as a member in family of peroxiredoxins in kinetoplastida. Method: Regarding the literature review on tryparedoxin peroxidase in kinetoplastida, the role and function of this important protein have been reviewed. Results: This protein with the critical function could be considered as a drug target. Also, it could be highlighted in vaccine development. Conclusion: This group of antioxidants plays an important role in various physiological and pathological processes including metabolism, defense, cell signaling and apoptosis. In this study, the functional tryparedoxin peroxidase of Leishmania spp. is reviewed.

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. Objective: The objective of this review is to extend the current knowledge in the field of biomaterials for TE and RM including human-made novel constructs though using different materials and strategies. Methods: We extensively reviewed, analyzed and compiled salient information from the authentic published literature available in PubMed and other scientific databases. Results: The multi-shape novel constructs have been fabricated for a variety of applications in bio and non-bio sectors of the modern world. As compared to the natural bulk material, engineering of their constructs particularly at the micro and nano-level impart unique characteristics including surface area and surface functionality enhancement, improved thermo-mechanical and electrical conductivity, etc. The materials-based engineered constructs have been exploited in biotechnology at large and biomedical in particular. Conclusion: The most promising applications include their utilization as a vehicle to deliver therapeutic agents, as scaffolds for engineering various tissues and also serve as an integrated part of biomedical implants, etc. Herein, we reviewed bio-nano-technological advancements from a TE and RM perspective in particular and envision directions of future developments.

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.

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. Objective: Characterization of all human miRs for nucleotide parameters and matching with mRNA sectors, and a comparison with fruitfly miRs as the original models. Method: Human and fruitfly miRs from miRBase v21 were examined for contents of GC nucleotides, strings and iterons and for matching with sectors of the respective mRNAs. Results: The > 1000-numbered ( > #1000) miRs represent a considerable majority (64%) of known human miRs and have much higher overall GC content (55% vs. 47%) and GC strings and iterons (61% and 81%, respectively) than the ≤ 1000-numbered (≤ #1000) miRs. The > #1000 miRs match mRNAs generally better than the ≤ #1000 group. Also, 3'utr are much better matched by human compared to fruitfly miRs, and human mRNA matches generally have much higher GC content and expected stability than those of fruitfly. Conclusion: Fruitfly miRs, while historically preferred in general miR modeling, are not a satisfactory model for human miRs. The current constriction of the medical evaluation of human microRNAs to the ≤ #1000 sequences with < 50% GC appears as quite arbitrary and mostly as related to research inertia. The mRNA matches of > #1000 miRs should be much more stable than those of the ≤ #1000 group. The miRs of high GC content have been found active in regulation of growth factors and transcription factors in many physiological as well as pathological paradigms, and seem to have considerable medical potential (including that in regenerative medicine), which should be adequately explored.