Characterization of a Chimeric Resilin-Elastin Structural Protein Dedicated to 3D Bioprinting as a Bioink Component.

In this study we propose to use for bioprinting a bioink enriched with a recombinant RE15mR protein with a molecular weight of 26 kDa, containing functional sequences derived from resilin and elastin. The resulting protein also contains RGD sequences in its structure, as well as a metalloproteinase cleavage site, allowing positive interaction with the cells seeded on the construct and remodeling the structure of this protein in situ. The described protein is produced in a prokaryotic expression system using an E. coli bacterial strain and purified by a process using a unique combination of known methods not previously used for recombinant elastin-like proteins. The positive effect of RE15mR on the mechanical, physico-chemical, and biological properties of the print is shown in the attached results. The addition of RE15mR to the bioink resulted in improved mechanical and physicochemical properties and promoted the habitation of the prints by cells of the L-929 line.

Graphene Oxide (GO)-Based Bioink with Enhanced 3D Printability and Mechanical Properties for Tissue Engineering Applications.

Currently, a major challenge in material engineering is to develop a cell-safe biomaterial with significant utility in processing technology such as 3D bioprinting. The main goal of this work was to optimize the composition of a new graphene oxide (GO)-based bioink containing additional extracellular matrix (ECM) with unique properties that may find application in 3D bioprinting of biomimetic scaffolds. The experimental work evaluated functional properties such as viscosity and complex modulus, printability, mechanical strength, elasticity, degradation and absorbability, as well as biological properties such as cytotoxicity and cell response after exposure to a biomaterial. The findings demonstrated that the inclusion of GO had no substantial impact on the rheological properties and printability, but it did enhance the mechanical properties. This enhancement is crucial for the advancement of 3D scaffolds that are resilient to deformation and promote their utilization in tissue engineering investigations. Furthermore, GO-based hydrogels exhibited much greater swelling, absorbability and degradation compared to non-GO-based bioink. Additionally, these biomaterials showed lower cytotoxicity. Due to its properties, it is recommended to use bioink containing GO for bioprinting functional tissue models with the vascular system, e.g., for testing drugs or hard tissue models.

Bioprinting of Perfusable, Biocompatible Vessel-like Channels with dECM-Based Bioinks and Living Cells.

There is a growing interest in the production of bioinks that on the one hand, are biocompatible and, on the other hand, have mechanical properties that allow for the production of stable constructs that can survive for a long time after transplantation. While the selection of the right material is crucial for bioprinting, there is another equally important issue that is currently being extensively researched-the incorporation of the vascular system into the fabricated scaffolds. Therefore, in the following manuscript, we present the results of research on bioink with unique physico-chemical and biological properties. In this article, two methods of seeding cells were tested using bioink B and seeding after bioprinting the whole model. After 2, 5, 8, or 24 h of incubation, the flow medium was used in the tested systems. At the end of the experimental trial, for each time variant, the canals were stored in formaldehyde, and immunohistochemical staining was performed to examine the presence of cells on the canal walls and roof. Cells adhered to both ways of fiber arrangement; however, a parallel bioprint with the 5 h incubation and the intermediate plating of cells resulted in better adhesion efficiency. For this test variant, the percentage of cells that adhered was at least 20% higher than in the other analyzed variants. In addition, it was for this variant that the lowest percentage of viable cells was found that were washed out of the tested model. Importantly, hematoxylin and eosin staining showed that after 8 days of culture, the cells were evenly distributed throughout the canal roof. Our study clearly shows that neovascularization-promoting cells effectively adhere to ECM-based pancreatic bioink. Summarizing the presented results, it was demonstrated that the proposed bioink compositions can be used for bioprinting bionic organs with a vascular system formed by endothelial cells and fibroblasts.

Bioprinted 3D Bionic Scaffolds with Pancreatic Islets as a New Therapy for Type 1 Diabetes-Analysis of the Results of Preclinical Studies on a Mouse Model.

Recently, tissue engineering, including 3D bioprinting of the pancreas, has acquired clinical significance and has become an outstanding potential method of customized treatment for type 1 diabetes mellitus. The study aimed to evaluate the function of 3D-bioprinted pancreatic petals with pancreatic islets in the murine model. A total of 60 NOD-SCID (Nonobese diabetic/severe combined immunodeficiency) mice were used in the study and divided into three groups: control group; IsletTx (porcine islets transplanted under the renal capsule); and 3D bioprint (3D-bioprinted pancreatic petals with islets transplanted under the skin, on dorsal muscles). Glucose, C-peptide concentrations, and histological analyses were performed. In the obtained results, significantly lower mean fasting glucose levels (mg/dL) were observed both in a 3D-bioprint group and in a group with islets transplanted under the renal capsule when compared with untreated animals. Differences were observed in all control points: 7th, 14th, and 28th days post-transplantation (129, 119, 118 vs. 140, 139, 140; p < 0.001). Glucose levels were lower on the 14th and 28th days in a group with bioprinted petals compared to the group with islets transplanted under the renal capsule. Immunohistochemical staining indicated the presence of secreted insulin-living pancreatic islets and neovascularization within 3D-bioprinted pancreatic petals after transplantation. In conclusion, bioprinted bionic petals significantly lowered plasma glucose concentration in studied model species.

Single-center experience with perioperative antibiotic prophylaxis and surgical site infections in kidney transplant recipients.

BACKGROUND: Infections in kidney transplant recipients are particularly challenging owing to the immunosuppressive treatment, usually long history of chronic illness, comorbidities and prior exposures to antibiotics. Among the most common complications early after surgery are surgical site infections. The aim of this study was to identify risk factors and evaluate epidemiological data regarding surgical site infections. Moreover, we were able to compare the current results with historical data from our institution when different perioperative antibiotic prophylaxis was practiced. METHODS: We conducted a retrospective case-control study in a group of 254 deceased donor renal graft recipients transplanted in a single Central European institution. We evaluated epidemiological findings and resistance patterns of pathogens causing surgical site infections. We used multivariable logistic regression to determine risk factors for surgical site infections. RESULTS: We revealed no differences in baseline characteristics between patients with and without surgical site infections. Ten surgical site infections (3.9%) were diagnosed (six superficial incisional, two deep incisional, and two organ/space). Eight species (19 strains) were identified, most of which were multi-drug resistant (63%). The most common was extended-spectrum ß-lactamase producing Klebsiella pneumoniae (26%). We showed that statistically significant differences were present between reoperated and non-reoperated patients (adjusted odds ratio: 6.963, 95% confidence interval 1.523-31.842, P = .012). CONCLUSIONS: Reoperation is an individual risk factor for surgical site infection after kidney transplantation. According to our experience, cefazolin-based prophylaxis can be safe and is associated with relatively low prevalence of surgical site infections.

Streptozotocin-Induced Diabetes in a Mouse Model (BALB/c) Is Not an Effective Model for Research on Transplantation Procedures in the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is characterized by the destruction of over 90% of the ß-cells. C-peptide is a parameter for evaluating T1D. Streptozotocin (STZ) is a standard method of inducing diabetes in animals. Eight protocols describe the administration of STZ in mice; C-peptide levels are not taken into account. The aim of the study is to determine whether the STZ protocol for the induction of beta-cell mass destruction allows for the development of a stable in vivo mouse model for research into new transplant procedures in the treatment of type 1 diabetes. Materials and methods: Forty BALB/c mice were used. The animals were divided into nine groups according to the STZ dose and a control group. The STZ doses were between 140 and 400 mg/kg of body weight. C-peptide was taken before and 2, 7, 9, 12, 14, and 21 days after STZ. Immunohistochemistry was performed. The area of the islet and insulin-/glucagon-expressing tissues was calculated. Results: Mice who received 140, 160, 2 × 100, 200, and 250 mg of STZ did not show changes in mean fasting C-peptide in comparison to the control group and to day 0. All animals with doses of 300 and 400 mg of STZ died during the experiment. The area of the islets did not show any differences between the control and STZ-treated mice in groups below 300 mg. The reduction of insulin-positive areas in STZ mice did not exceed 50%. Conclusions: Streptozotocin is not an appropriate method of inducing a diabetes model for further research on transplantation treatments of type 1 diabetes, having caused the destruction of more than 90% of the ß-cell mass in BALB/c mice.

Chitosan as an Underrated Polymer in Modern Tissue Engineering.

Chitosan is one of the most well-known and characterized materials applied in tissue engineering. Due to its unique chemical, biological and physical properties chitosan is frequently used as the main component in a variety of biomaterials such as membranes, scaffolds, drug carriers, hydrogels and, lastly, as a component of bio-ink dedicated to medical applications. Chitosan's chemical structure and presence of active chemical groups allow for modification for tailoring material to meet specific requirements according to intended use such as adequate endurance, mechanical properties or biodegradability time. Chitosan can be blended with natural (gelatin, hyaluronic acid, collagen, silk, alginate, agarose, starch, cellulose, carbon nanotubes, natural rubber latex, κ-carrageenan) and synthetic (PVA, PEO, PVP, PNIPPAm PCL, PLA, PLLA, PAA) polymers as well as with other promising materials such as aloe vera, silica, MMt and many more. Chitosan has several derivates: carboxymethylated, acylated, quaternary ammonium, thiolated, and grafted chitosan. Its versatility and comprehensiveness are confirming by further chitosan utilization as a leading constituent of innovative bio-inks applied for tissue engineering. This review examines all the aspects described above, as well as is focusing on a novel application of chitosan and its modifications, including the 3D bioprinting technique which shows great potential among other techniques applied to biomaterials fabrication.

Stem Cells as a Source of Pancreatic Cells for Production of 3D Bioprinted Bionic Pancreas in the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Often, intensive insulin therapy is insufficient, and patients require a pancreas or pancreatic islets transplant. However, both solutions are associated with many possible complications, including graft rejection. The best approach seems to be a donor-independent T1D treatment strategy based on human stem cells cultured in vitro and differentiated into insulin and glucagon-producing cells (ß and α cells, respectively). Both types of cells can then be incorporated into the bio-ink used for 3D printing of the bionic pancreas, which can be transplanted into T1D patients to restore glucose homeostasis. The aim of this review is to summarize current knowledge about stem cells sources and their transformation into key pancreatic cells. Last, but not least, we comment on possible solutions of post-transplant immune response triggered stem cell-derived pancreatic cells and their potential control mechanisms.

Impact of Porcine Pancreas Decellularization Conditions on the Quality of Obtained dECM.

Due to the limited number of organ donors, 3D printing of organs is a promising technique. Tissue engineering is increasingly using xenogeneic material for this purpose. This study was aimed at assessing the safety of decellularized porcine pancreas, together with the analysis of the risk of an undesirable immune response. We tested eight variants of the decellularization process. We determined the following impacts: rinsing agents (PBS/NH3·H2O), temperature conditions (4 °C/24 °C), and the grinding method of native material (ground/cut). To assess the quality of the extracellular matrix after the completed decellularization process, analyses of the following were performed: DNA concentration, fat content, microscopic evaluation, proteolysis, material cytotoxicity, and most importantly, the Triton X-100 content. Our analyses showed that we obtained a product with an extremely low detergent content with negligible residual DNA content. The obtained results confirmed the performed histological and immuno-fluorescence staining. Moreover, the TEM microscopic analysis proved that the correct collagen structure was preserved after the decellularization process. Based on the obtained results, we chose the most favorable variant in terms of quality and biology. The method we chose is an effective and safe method that gives a chance for the development of transplant and regenerative medicine.

Bionic Organs: Shear Forces Reduce Pancreatic Islet and Mammalian Cell Viability during the Process of 3D Bioprinting.

BACKGROUND: 3D bioprinting is the future of constructing functional organs. Creating a bioactive scaffold with pancreatic islets presents many challenges. The aim of this paper is to assess how the 3D bioprinting process affects islet viability. METHODS: The BioX 3D printer (Cellink), 600 µm inner diameter nozzles, and 3% (w/v) alginate cell carrier solution were used with rat, porcine, and human pancreatic islets. Islets were divided into a control group (culture medium) and 6 experimental groups (each subjected to specific pressure between 15 and 100 kPa). FDA/PI staining was performed to assess the viability of islets. Analogous studies were carried out on α-cells, ß-cells, fibroblasts, and endothelial cells. RESULTS: Viability of human pancreatic islets was as follows: 92% for alginate-based control and 94%, 90%, 74%, 48%, 61%, and 59% for 15, 25, 30, 50, 75, and 100 kPa, respectively. Statistically significant differences were observed between control and 50, 75, and 100 kPa, respectively. Similar observations were made for porcine and rat islets. CONCLUSIONS: Optimal pressure during 3D bioprinting with pancreatic islets by the extrusion method should be lower than 30 kPa while using 3% (w/v) alginate as a carrier.

Novel Strategies in Artificial Organ Development: What Is the Future of Medicine?

The technology of tissue engineering is a rapidly evolving interdisciplinary field of science that elevates cell-based research from 2D cultures through organoids to whole bionic organs. 3D bioprinting and organ-on-a-chip approaches through generation of three-dimensional cultures at different scales, applied separately or combined, are widely used in basic studies, drug screening and regenerative medicine. They enable analyses of tissue-like conditions that yield much more reliable results than monolayer cell cultures. Annually, millions of animals worldwide are used for preclinical research. Therefore, the rapid assessment of drug efficacy and toxicity in the early stages of preclinical testing can significantly reduce the number of animals, bringing great ethical and financial benefits. In this review, we describe 3D bioprinting techniques and first examples of printed bionic organs. We also present the possibilities of microfluidic systems, based on the latest reports. We demonstrate the pros and cons of both technologies and indicate their use in the future of medicine.

The Influence of the Flow of Detergent and Donor Characteristics on the Extracellular Matrix Composition After Human Pancreas Decellularization.

INTRODUCTION: The extracellular matrix (ECM) consists, among others, of polysaccharides, glycosaminoglycans, and proteins. It is being increasingly used in tissue bioengineering. Obtaining ECM of the highest quality through decellularization is a big challenge because of some differences in organ structure. To deprive organs of the cellular part, chemical, enzymatic, or mechanical methods are used. After decellularization, we get a scaffold made of a variety of proteins, and it is the role of these proteins that can significantly affect the maintenance of the spatial structure and be a suitable environment for cells to rebuild a specific organ. AIM: Estimation of the detergent (Triton X-100) flow parameters and anthropometric donors' decellularization process accuracy on the final ECM composition. MATERIALS: Five human pancreata, rejected from transplantation, were used for decellularization. All organs were harvested from brain-dead donors age 13 to 60 years. METHODS: Decellularization was carried out using the flow method with Triton X-100 as an active agent. The experiment compared 5 different flow values. After decellularization, an assessment of the final DNA concentration and the protein composition was performed. Results were compared to anthropometric data of donors. In addition, a microscopic analysis was also carried out. RESULTS: The best results were obtained using a flow of 120 mL/minute. A higher detergent flow was associated with a lower concentration of residual DNA in scaffold. Analysis of the protein profile with anthropometric data has shown that LAM A2 was increasing with age and LAMA5 was decreasing. Being overweight was associated with a higher proportion of COL1 and 4 and a smaller proportion of COL6.

Crosstalk Between Immunity System Cells and Pancreas. Transformation of Stem Cells Used in the 3D Bioprinting Process as a Personalized Treatment Method for Type 1 Diabetes.

Interactions between the immune system and the pancreas are pivotal in understanding how and why ß cells' damage causes problems with pancreas functioning. Pancreatic islets are crucial in maintaining glucose homeostasis in organs, tissue and cells. Autoimmune aggression towards pancreatic islets, mainly ß cells, leads to type 1 diabetes-one of the most prevalent autoimmune disease in the world, being a worldwide risk to health of many people. In this review, we highlight the role of immune cells and its influence in the development of autoimmunity in Langerhans islets. Moreover, we discuss the impact of the immunological factors on future understanding possible recurrence of autoimmunity on 3D-bioprinted bionic pancreas.

Type 1 diabetes: genes associated with disease development.

Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Based on the World Health Organization (WHO) report from 2014 the number of people suffering from all types of diabetes ascended to 422 million, compared to 108 million in 1980. It was calculated that this number will double by the end of 2030. In 2015 American Diabetes Association (ADA) announced that 30.3 million Americans (that is 9.4% of the overall population) had diabetes of which only approximately 1.25 million had T1D. Nowadays, T1D represents roughly 10% of adult diabetes cases total. Multiple genetic abnormalities at different loci have been found to contribute to type 1 diabetes development. The analysis of genome-wide association studies (GWAS) of T1D has identified over 50 susceptible regions (and genes within these regions). Many of these regions are defined by single nucleotide polymorphisms (SNPs) but molecular mechanisms through which they increase or lower the risk of diabetes remain unknown. Genetic factors (in existence since birth) can be detected long before the emergence of immunological or clinical markers. Therefore, a comprehensive understanding of the multiple genetic factors underlying T1D is extremely important for further clinical trials and development of personalized medicine for diabetic patients. We present an overview of current studies and information about regions in the human genome associated with T1D. Moreover, we also put forward information about epigenetic modifications, non-coding RNAs and environmental factors involved in T1D development and onset.

Time of Cold Storage Prior to Start of Hypothermic Machine Perfusion and Its Influence on Graft Survival.

BACKGROUND: Hypothermic machine perfusion (HMP) has become a standard method of preservation for kidneys procured from expanded-criteria donors and donors after cardiac death. There are different systems and approaches to the HMP preservation period, with cold storage prior to HMP sometimes taking several hours. This study evaluated whether the time at which kidneys receive HMP had any influence on the outcomes of kidney transplantation. METHODS: In this analysis, patient and graft survival were evaluated over a 1-year post-transplantation period. Patients who received HMP kidneys (n = 379) were divided into 2 groups: those who received kidneys with a cold ischemia time (CIT) prior to HMP <295 minutes (group G1; n = 254) and those who received kidneys with CIT prior to HMP >295 minutes (group G2; n = 125). RESULTS: Delayed graft function was observed in 31.8% (81/254) of patients in group G1 vs 46.4% (58/125) of patients in group G2 (P = .007). One-year graft survival was statistically higher in the group G1 (93.2%; 233/254) vs group G2 (86.5%; 105/125, P = .029). Mean 1-year estimated glomerular filtration rate was significantly better in the group G1. CONCLUSIONS: In conclusion, introduction of HMP up to 295 minutes from procurement led to better early and 1-year graft results. Kidneys should receive HMP as soon as possible after retrieval, preferably during procurement.

Reoperation in Early Kidney Post-transplant Period as a Strong Risk Factor of Surgical Site Infection Occurrence.

BACKGROUND: One of the most common infective complications after kidney transplant (KTx) is surgical site infection (SSI). Providing indications of improvement of perioperative antibiotic prophylaxis (PAP) and allowing the characterization of risk factors are critical to reduce SSI. The purpose of this study was to evaluate the SSI risk factors and impact of reoperation in the early post-transplant period on SSI occurrence and assess if standard PAP in those cases is a best consideration. METHODS: Between April 2014 and October 2015, a total of 236 KTxs were performed in our center. Deceased donor data, recipient data, and data related to surgical procedures were collected. RESULTS: Surgical site infections were reported in 5.6% (12/214) of patients. Seven patients were diagnosed as having superficial SSI (7/12; 58.3%), 2 with deep SSI (2/12; 16.6%), and 4 with organ-specific SSI (4/12; 33.3%). Extended criteria donor-related transplant, cold ischemia time > 22 hours, dialysis period > 30 months, recipient age older than 45 years, recipient body mass index > 27, induction therapy prior to transplant, diabetes prior to transplant, and ≥ 1 reoperation during 30 days of observation were independent risk factors of SSI occurrence. A total of 19 reoperations were performed in 17 patients. In 8 of all 12 patients with SSI diagnosis, the reoperation was performed (66.7%). In 202 patients of non-SSI patients, only 9 reoperations were performed (4.5%). CONCLUSIONS: Early reoperation after Ktx is a strong risk factor of SSI occurrence. There is a probability that > 4 SSI risk factors and reoperation in the early post-transplant period could require different and more aggressive proceeding, as standard PAP in those cases is insufficient.

Should Immunosuppression After Kidney Transplant Be Adjusted Based on Renal Resistance During Pretransplant Hypothermic Machine Perfusion?

BACKGROUND: The hypothermic machine perfusion reduces delayed graft function after kidney transplant and allows, to some extent, predicting early graft function. However, it is difficult to identify exact perfusion criteria with which to exclude kidneys from transplant or modify post-transplant care. The aim of this study was to analyze whether renal resistance during the fourth hour of hypothermic machine perfusion is useful in the prediction of graft survival and acute rejection. PATIENTS AND METHODS: Data on pretransplant hypothermic machine perfusion parameters of 407 transplanted kidneys were available. Receiver operating characteristic curve analysis was performed to find an optimal cutoff value of ratio for predicting a higher risk class of considered group of patients. According to this, patients were divided into 2 groups: those who received kidneys with renal resistance lower than 0.19 mm Hg/mL/min (R1; n = 187) and those who received kidneys with renal resistance equal to or higher than 0.19 mm Hg/mL/min (R2; n = 220). Within R2, we additionally analyzed 2 subgroups: patients who received induction therapy (R2-Ind+; n = 124) and those who did not received induction therapy (R2-Ind-; n = 96). RESULTS: Acute rejection in R1 within 1 month post transplant was 2-fold lower compared with R2 and was 6.4% vs 13.1% (P = .03), respectively. One-year graft survival was higher in R1 compared with R2 and was 94.6% vs 88.5% (P = .03), respectively. Acute rejection in the R2-Ind+ subgroup within 1 month post transplant was 2.46-fold lower compared with the R2-Ind- subgroup and was 8% vs 19.7% (P = .01), respectively. CONCLUSION: Immunosuppression treatment after transplant should be adjusted to perfusion parameters.

Predictors of Acute Kidney Injury in Deceased Kidney Donors After Brain Death.

BACKGROUND: Donors with acute kidney injury (AKI) are generally accepted as a valuable source of kidneys for transplant. The aim of this study was to assess the risk of developing AKI based on deceased kidney donor parameters. MATERIALS AND METHODS: The data of 162 kidneys procured from deceased donors after brain death were collected. These included clinical characteristics of donors and histologic assessment in organ biopsy specimens. The donors' kidney terminal function was classified according to the Acute Kidney Injury Network criteria. All biopsies were performed with the use of a 16G automatic needle, and the 20-mm tissue specimen was available in all cases. Biopsy specimens were secured and prepared in a routine way with hematoxylin and eosin. The presence of chronic changes was analyzed according to the Banff 2009 classification by 1 experienced nephropathologist. The logistic regression model was used to assess the risk of AKI regarding donor characteristics and histologic findings. RESULTS: There were 50 kidneys (30.9%) with AKI identified. The risk of AKI increased with donor age (P = .002; odds ratio [OR], 1.02; 95% CI, 1.01-1.03), body mass index (P = .003; OR, 1.05; 95% CI, 1.01-1.09), and male sex (P = .001; OR, 1.79; 95% CI, 1.31-2.27). Regarding the histologic findings, the interstitial fibrosis presence was a risk factor of AKI (P = .004; OR, 1.04; 95% CI, 1.01-1.06). CONCLUSIONS: Older donor age, male sex, higher body mass index, and presence of interstitial fibrosis in kidney graft biopsy specimen are risk factors of AKI.

Do We Need Insulin Independence After Islet Transplantation?

INTRODUCTION: Most life-threatening diabetes-related complications involve the kidneys, eyes, cardiovascular system, and autonomic nervous system. Clinical islet transplantation (CITx) may be a therapeutic option for some patients. In this study, we analyzed the progression of diabetic complications after CITx and in patients waiting for islet transplantation. METHODS: From 2008 to 2015, 67 patients were listed for pancreatic or islet transplantation. We compared beta scores, islet scores, and secondary complications between patients who underwent islet allotransplantation (CITx group, n = 6) and the patients awaiting islet transplantation (wait group, n = 19) at baseline and during the 1-year follow-up. RESULTS: In the CITx group, good islet function was observed in 80% of patients 1 month post-transplantation and 40% of patients 1 year post-transplantation; however, no patient achieved insulin independence. One patient who underwent simultaneous islet-kidney transplantation died on day 8 because of severe bleeding in the retroperitoneal space. In 1 case, islet primary nonfunction was observed. Mean islet score in the CITx group 1 year post-transplantation was significantly higher than the pretransplant score and wait group scores at enrollment and 1 year later (P < .01). Increased albuminuria was observed in 3 of 11 (27%) patients in the wait group and 0 patients in the CITx group (P = .08). One patient (9%) in the wait group developed chronic renal failure requiring hemodialysis. Ophthalmologic procedures were required by 47% of patients in the wait group and 0 patients in the CITx group in the first year after transplantation (P < .01). CONCLUSION: Successful islet transplantation slows the progression of diabetic complications.

Islet Autotransplantation in Diabetic Patients.

INTRODUCTION: Painful chronic pancreatitis (CP) is the main indication for analgesic pancreatectomy with simultaneous islet autotransplantation to prevent postoperative diabetes mellitus (DM). However, advanced CP may lead to insulin secretion disorders and DM. There are doubts as to whether islet autotransplantation in such cases is an appropriate procedure. The aim of this study was to analyze the results of islet autotransplantation in patients with CP with already diagnosed with DM. METHOD: Between 2008 and 2015, at the Department of General and Transplantation Surgery, patients with CP and unsatisfying pain treatment with positive fasting C-peptide ( > 0.3 ng/mL) level were qualified for simultaneous pancreatectomy and islet autotransplantation. Eight procedures were performed. In 5 cases patients had DM diagnosed prior to the procedure (DM group n = 5). Three patients without DM diagnosed prior to surgery were the control group (n = 3). RESULT: There were no cases of procedure-related deaths in either group. Pain relief without analgesics was reported by all patients. Good islet function was observed in 80% (4/5) of the DM group vs 100% (3/3) in the control group (P = ns). Brittle diabetes was diagnosed in 1 patient in the DM group as a result of islet primary non-function. CONCLUSION: Patients with CP-related severe pain and DM patients with positive C-peptides should be considered for pancreatectomy and islet autotransplantation.