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Regenerative medicine has attempted to raise hopes to replace failing solid organs as a part of its wide-spectrum mission over the last couple of decades. To generate and implant an organ, taking the global challenge of organ shortage and histological complexity into consideration, has made this endeavor more taxing and strenuous in comparison with other subjects including cells and tissues. As the most prevalent transplanting organ worldwide, to make a kidney in laboratories using decellularized discarded donated kidney as a scaffold and recullalarize that with recipient's native cells to circumvent another unavoidable obstacle, immunological mismatch, has remained a not yet attainable promise. Diversity of cell types and structural complexity of kidney with a range of functions has slowed down the pace of taking steps to fulfill this outstanding ambition, and, accordingly, it would make sense for the nonce that main attempts in limited-funding settings shall be directed to procure more allogenic grafts to partially meet the daily-expanding demands.

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Solid organ transplant recipients are in high demand for developed immune-modulating agents to control allo-immune responses following transplantation. The immunosuppressive agents offer the recipients improved short-term graft survival; nonetheless, this benefit is tempered by unavoidable long-term adverse events of these medications. Active control of allo-response using therapeutic cell transfer has gained much attraction during the last few years. It is widely established that regulatory T cells (Tregs) control immune responsiveness to allo-antigens and contribute to the induction of tolerance. Here, it is aimed to review recent results regarding Tregs and chimeric antigen receptor (CAR) Tregs therapy in solid organ transplantation and discuss strategies to overcome technical challenges of developing successful Tregs/CAR Tregs therapy.

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Using external fixtures for bone deformity correction takes advantages of less soft tissue injury, better bone alignment and enhances strain development for bone formation on cutting section, which cause shorter healing time. Among these fixtures, Taylor spatial frame is widely used and includes two rings and six adjustable struts developing 6 degrees of freedom, making them very flexible for this type of application. The current study describes a method to optimize Taylor spatial frame pin-sizes currently chosen from the surgeon's experiences. A three-dimensional model of femur was created from computed tomography images; segmentation of the medical images was made based on the Hounsfield unit (gray scale) in order to allocate adequate mechanical properties into cortical and trabecular bone sections. Both the cortical and trabecular sections were assumed to be isotropic and homogeneous. The diameter optimization of Taylor spatial frame's half-pins was carried out by coupling genetic algorithm and finite element analysis. The finite element analysis was based on a static mechanical load corresponding to a standing person's body weight. Finite element analysis results were validated with experimentally measured strains obtained from bone compression tests. A cost function, based on the developed bone stresses, was defined close to the Taylor spatial frame's half-pins. The calculated cost function showed a decrease of over 33% from the initial half-pin selection by the surgeon and the genetic algorithm optimization. Consequently, the maximum stresses experienced by the bone in the connected location of the half-pins decreased from 121.4 MPa in the surgeon's selection to 73.07 MPa as a result of the optimization process.

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Microbiological screening of tissue allografts is crucial to prevent the transmission of bacterial and fungal infections to transplant recipients. Klebsiella was the most prevalent and resistant contaminating microorganism observed in our setting in the Iranian Tissue Bank. This study was conducted to determine the presence of extended-spectrum ß-lactamase (ESBL) genes, antimicrobial resistance patterns of Klebsiella pneumoniae isolates, and their clonal relationships in allograft materials. K. pneumoniae contaminating bone and other tissue allografts recovered from deceased donors were identified and ESBL isolates were detected using a phenotypic confirmatory method. Antimicrobial susceptibility testing was carried out using the disk diffusion method. Distribution of ESBL genes and molecular typing were performed using polymerase chain reaction (PCR) and Repetitive-element (rep-PCR) methods. Of 3828 donated tissues, 51 (1.3%) were found contaminated by K. pneumoniae isolates. Compared to tissue allografts from brain-dead, heart-beating tissue donors, allografts from donors with circulatory cessation were associated with a higher risk of K. pneumoniae contamination [odds ratio (OR), 1.2 (CI 95% 0.9-2.3) (P value < 0.001)]. Half of the isolates produced ESBL, and the rate of susceptibility to cephalosporins was 51%. Among isolates, 22 (43.1%) harbored CTX-M, 31 (60.8%) SHV, and 9 (17.6%) harbored TEM types. The rep-dendrogram indicated that clones having identical or related strains with a similar antibiotype were isolated in the same period. This study provides evidence that a single clone of K. pneumoniae contaminated tissue allografts recovered from many different donors. A single clone found on tissues from several donors suggests contamination of tissues from a single source such as the tissue recovery process and environment. Genomic DNA testing and clonality of contaminating bacteria using molecular methods can focus the epidemiologic investigation on the tissue allograft recovery process including a search for contamination of the tissue recovery room environment, recovery staff, recovery equipment, reagents, solutions and supplies.

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AIM: To bridge the gap in the current knowledge, the present study was conducted to obtain evidences relating to clinical outcomes of the end-stage renal disease (ESRD) population in Iran over the last two decades. METHODS: The records of 84 652 incident ESRD patients from 1995 up to and including 2014 in the national registry of ESRD patients were analyzed retrospectively. Data were collected from dialysis and transplant centres in Iran from 1995 to 2008 via paper forms and from 2009 to 2014 through web-based records. RESULTS: Mean age (SD) in incident cases of ESRD (57.7% male) was 52.5 (16.6) years. The prevalence of ESRD patients grew on average 14.9% and 5.3% annually in the periods of 1995-2004 and 2005-2014, respectively. Adjusted mortality rate among dialysis patients in 1995, 2005, and 2014 was 145, 154, and 177/ 1000 patient-years, respectively. Median graft half-life (IQR) and median expected remaining life-years (IQR) for dialysis patients in the 2003 incident patient cohort were 4.4 (1.9-8.3) and 4.2 (1.8-8.2) years, respectively. CONCLUSIONS: The overall slightly decreasing, and still comparable, survival trend in dialysis patients, despite the accessible and free dialysis treatment, may be the result of the counterbalance of different contributory factors, including increased age and the higher proportion of patients with co-morbidities resulting from diabetes and hypertension. The half-lives of renal allografts were generally shorter compared to thus far shared evidence, which may be due to tissue incompatibility. The decreasing trend, in this context, can be attributable to the increased number of transplantation from deceased donors with expanded criteria.

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Durability and the rate of complications of homograft heart valves, adjusted for patient-related contributors and surgical techniques, rely mainly on the quality of allografts which in turn are mirrored in the donor characteristics and most importantly recovery and processing procedures. Aimed to assess the quality, a study was conducted to figure out the durability and late outcome following homograft replacement with valved conduits procured by the Iranian Tissue Bank. Retrospectively, the pre-implantation, perioperative and follow-up data of 400 non-consecutive recipients of cryopreserved heart valves (222 pulmonary and 178 aortic) from 2006 to 2015 were collected and analyzed in terms of variables reflecting late outcome including adverse events and durability. In the context of durability, the event of interest was defined as the need for homograft replacement and homograft-related death. The mean follow-up time (SD) of study entrants (male/female ratio, 1.4) was 49.8 (36.3) months. Median age at the time of implantation was 11 years. Total 10-years mortality was 21 % (84/400), including 66.7 % early (30-days mortality: 56/84) and 33.3 % late (28/84). Overall late complication rate was 2 %. Median survival time was 120 months (95 % CI 83.3-156.6). The pulmonary valves appeared to be more durable (P value <0.001) and survival probabilities in small sized grafts were lower (P value 0.008). One-, five-, and ten-year graft survival was 82, 76 and 73 %, respectively. The evidences suggest that the homografts function satisfactory with low rate of late complications; nevertheless, more emphasis should be given to make long-term durability comparable.

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Organ transplantation as an undeniable life-saving therapeutic modality fundamentally requires infrastructure, devoted and trained professionals, and positive public attitude to be set up in a well-organized manner at the national level. In addition to sharing achievements and reviewing the increasing trend of transplanted organs in the past 12 years following legislations in Iran, this report raises some concerns from the point of transplantation outcome view.

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INTRODUCTION: The rapid increase in the prevalence of end-stage renal disease (ESRD) necessitates putting into practice some strategies to prevent its development and progression, especially in the developing world. Detailed chronological changes in the incidence of ESRD may sharpen the focus on its prevention. We, therefore, determined the detailed epidemiological features of ESRD in Iran. MATERIALS AND METHODS: Data of the national registry of Iran's ESRD provided by the Ministry of Health were used to retrieve the ESRD figures between 1997 and 2006. RESULTS: A total of 35 859 patients who initiated renal replacement therapy (20 633 men and 15 226 women) were registered during the study period from 1997 to 2006. The annual number of patients with ESRD beginning maintenance treatment in Iran increased 130% between 2000 and 2006. During 1997 to 2006, the proportion of new cases of ESRD attributed to diabetes mellitus increased 2-fold from 16% in 1997 to 31% in 2006. The mean age of newly registered men and women increased from 47.0 years and 49.0 years to 52.5 years and 53.0 years, respectively. As for all and major causes of ESRD, age-adjusted incidence rates for men generally were higher than those for women. Male-female ratio was 1.3:1, with no significant changes during this period. CONCLUSIONS: We strongly recommend considering chronic kidney disease prevention with initial focusing on strategies and treatment modalities that slow ESRD progression in order to postpone the need for renal replacement therapy.

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INTRODUCTION: Living unrelated kidney donation has a high rate in Iran, where a unique organ procurement model is running. We evaluated feelings and attitude of these donors after kidney donation. MATERIALS AND METHODS: A questionnaire was sent to 25 kidney transplantation centers in Iran. It was designed to assess kidney allograft donors in terms of their reason for donation, their feeling after donation, and their attitude on keeping in touch with the recipients. Of 721 donors recorded in the national registry during the study period, we collected data of 600 living donors and their answers to the questionnaire. RESULTS: Of 600 donors, 495 (82.5%) were men and 568 (94.8%) were unrelated to the recipients. Motivation for donation was stated to be purely financial by 224 respondents (37.3%) and purely altruistic by 11 (1.9%). Their feelings before discharge were complete satisfaction in 519 (86.5%), relative satisfaction in 69 (11.5%), regret in 9 (1.5%), and indifference in 3 (0.5%). Willingness to get informed of the transplant outcome and make connection with the recipient following transplantation was chosen by 457 (76.2%) and 400 (66.7%) donors, respectively. CONCLUSIONS: We found that satisfaction of donors shortly after donation, on the one hand, and no reportedly serious complications in long-term follow-up of donors, on the other hand, may give the impression that the Iranian model may solve the problem of increasing demand for kidney allograft. Nevertheless, every country should build its own standards for living unrelated kidney donation consistent with its capacities and resources.

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The purpose of this study was to assess the health service cost of hemodialysis (HD) delivered at hospitals in Iran as a developing country with a well-defined program of renal replacement therapy. A cost analysis was performed from the viewpoint of the 2 hospitals, with 3 shifts and full chairs, on current practice for dialysis maintenance. Cost and patient data were collected in 2006 and from April 1 to May 31, 2007, respectively. A total of 22,464 HD sessions were performed and 247 patients were studied during the study period. The reference year for the value of USD for different mentioned costs was 2006. Health care sector costs associated with each HD session were estimated at US$78.87. Most of the total maintenance expenditure was made up of medical supplies (36.19%), with dialyzers as the major cost driver. Staff salaries represented 17% of the cost and fixed direct capital costs accounted for 21.4%. Of the family members, 32.4% accompanied their patients. The mean cost for transportation of patients and accompanied person was US$3.15 +/- 2.83 and US$1.5 +/- 0.29, respectively. These findings are important in the light of limited available resources coupled with the increasing prevalence of kidney failure. A major attempt should also be made to increase peritoneal dialysis coverage as in some centers we cannot keep all chairs full, especially in some vast areas. It is highly recommended to place initial focus on strategies and treatments that slow disease progression, to postpone renal replacement therapy to save resources.

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INTRODUCTION: Our aim was to evaluate the degree of achievement of the recommended values in National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) guidelines for the laboratory indicators of bone metabolism in patients undergoing hemodialysis (HD) in Tehran province. MATERIALS AND METHODS: We evaluated the laboratory information of 2630 HD patients in Tehran province. Demographic data of the patients and the clinical information including the duration of dialysis session, dialysate calcium concentration, Kt/V, and serum values of calcium, phosphorus, and intact parathyroid hormone (PTH) were recorded. The laboratory values were compared to the recommended ranges by the K/DOQI work group in patients with end-stage renal disease. RESULTS: Only 1.8% of the patients could enjoy a successful management according to the K/DOQI recommendations for the 4 target laboratory tests of serum calcium, phosphorus, intact parathyroid hormone, and calcium-phosphorus product. Hypocalcemia was diagnosed in 33.2% of the patients, whereas 13.6% were diagnosed with hypercalcemia. Hypophosphatemia and secondary hyperparathyroidism were diagnosed in 6.8% and 24.2% of the patients, respectively. CONCLUSIONS: Our findings proved that complying with the recommendations established by the K/DOQI work group in the clinical management of mineral metabolism is very demanding. Phosphate binders frequently lead to untoward toxicities and imbalance in bone metabolism of patients on HD, warranting new cost-effective therapies with fewer side effects. It would be of great interest to analyze, in the future, the benefits derived from the effect of new therapies such as calcimimetics or new phosphate binders regarding the achievement of the K/DOQI guidelines.

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