Transplantation Control Group Research Articles

Acupoint transplantation versus non-acupoint transplantation using autologous peripheral blood mononuclear cells in treating peripheral arterial disease.

Numerous studies have discussed the therapeutic outcomes of using cell therapy or acupuncture to treat peripheral artery disease (PAD). However, there are no long-term studies on the safety and efficacy of transplanting peripheral blood mononuclear cells (PBMNCs) via acupoints to treat PAD. We first reviewed the short-term and long-term clinical results of PAD patients treated with PBMNCs through intramuscular non-acupoint transplantation (control group; n = 45) or intramuscular acupoint transplantation (acupoint group; n = 45) at a single university hospital general medical center between December 2002 and September 2022. Pain intensity (assessed with the verbal rating scale [VRS] score) in the acupoint group was considerably lower than that in the control group at month 1 (mean ± standard deviation [SD]: 1.29 ± 0.96 vs 1.76 ± 0.82; P = 0.016) and month 3 (mean ± SD: 1.27 ± 0.90 vs 1.61 ± 0.86; P = 0.042). We observed significant improvement of VRS score (P < .001 for all) and ankle-brachial index (ABI; P < .001 for all) from baseline in both groups at months 1, 3, 6, 12, 36, and 60. The 10-year cumulative rate of major amputation-free survival (MAFS) was higher in the acupoint group as compared to the control group (81.9%, 95% confidence interval [CI]: 71.3%-94.1% vs 78.5%, 95% CI: 66.7%-92.3%; P = 0.768). Compared with the routine injection method, intramuscular transplantation of PBMNCs via selected acupoints could significantly decrease the short-term pain intensity in patients with PAD, which remains an option for consideration.

Zinc-aspirin preconditioning reduces endothelial damage of arterial grafts in a rodent model of revascularization.

Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ischemia-reperfusion injury (IRI), which occurs during the harvest and implantation of the grafts, is an important determinant of graft patency. Preconditioning with aspirin, a nonsteroidal anti-inflammatory drug has been shown to reduce the functional and molecular damage of arterial grafts in a rodent model. Studies have found that the zinc-aspirin complex may be able to exert an even better protective effect in pathological cardiovascular conditions. Thus, our aim was to characterize the protective effect of zinc-aspirin complex on free arterial grafts in a rodent model of revascularization. Donor Lewis rats were treated with either zinc-aspirin, aspirin, or placebo (n = 8) for 5 days, then the aortic arches were harvested and stored in cold preservation solution and implanted heterotopically in the abdominal cavity of the recipient rats, followed by 2 h of reperfusion. There was also a non-ischemia-reperfusion control group (n = 8). Functional measurements using organ bath and histomorphological changes using immunohistochemistry were analyzed. The endothelium dependent maximal vasorelaxation was improved (non-transplanted control group: 82% ± 3%, transplanted control group: 14% ± 2%, aspirin group: 31% ± 4%, zinc-aspirin group: 52% ± 4%), the nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the groups preconditioned with aspirin or zinc-aspirin. However, zinc-aspirin proved to be more effective in the reduction of IRI, than aspirin alone. Preconditioning with zinc-aspirin could be a promising way to protect the function and structural integrity of free arterial grafts, thus improving the outcomes of CABG.

#2938 DE NOVO DSA IS ASSOCIATED WITH HUMAN PERIPHERAL BLOOD CXCR5+PD-1+CD8+ T CELLS AND PD-1 PD-L1 MRNA EXPRESSION IN KIDNEY TRANSPLANT PATIENTS

Abstract Background and Aims Donor-specific antibody (DSA) development is mainly responsible for chronic antibody-mediated rejection. The immunological events that cause the development of DSA is not fully elucidated. The relationship between the Follicular Cytotoxic T cell subgroup and the development of DSA is unknown. In this study we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in recipients who de-novo DSA positive or negative after kidney transplantation (KTX). Method In this study, the expression levels of PD-1, PD-L1 genes were determined using the Real-Time Quantitative PCR method from peripheral blood samples of 22 KTX patients with de-novo DSA positive, 20 KTX patients with DSA negative and 21 healthy control (Table 1). Our patient groups were PRA negative before transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data. Results PD-1 expression level was higher in the KTX patients with de-novo DSA positive compared to the KTX patients with DSA negative group (p:0.006 CT: 0,84±0,23). According to the results of flow cytometry, CD8+CXCR5+PD-1+ cell expression (%) levels were found to be significantly higher in patients (3,06±1,98) compared to the transplant control group (0,52±0,40) (p: 0.001) (Figure 1). Conclusion It shows that there may be a direct correlation between DSA and PD-1 / PDL-1 mRNA level and CXCR5+PD1+CD8+ follicular cytotoxic T cell in transplant patients after kidney transplantation.

Clinical Outcomes by Consolidation of Bone Marrow Stem Cell Therapy and Coronary Artery Bypass Graft in Patients With Heart Failure With Reduced Ejection Fraction: A Meta-analysis

Bone marrow stem cell (BMSC) transplantation during coronary artery bypass graft (CABG) is an innovative treatment for ischemic heart disease (IHD). We conduct a meta-analysis to examine whether patients with IHD presenting heart failure with reduced ejection fraction (HFrEF) can be beneficent from CABG with additional BMSC transplantation. Electronic searches were performed on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov from their inception to July 2021. The efficacy was based on left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), and 6-min walk test (6MWT) change after treatment. Eight randomized-controlled trials (RCTs) were included in this meta-analysis, with a total of 350 patients. Results showed BMSC transplantation significantly improved the LVEF [mean difference (MD) = 6.23%, 95% confidence interval (CI): 3.22%–9.24%, P < 0.0001], LVEDVi (MD = −20.15 ml/m2, 95% CI: −30.49 to −9.82 ml/m2, P < 0.00001), and LVESVi (MD = −17.69 ml/m2, 95% CI: −25.24 to −10.14 ml/m2, P < 0.00001). There was no statistically significant difference in the improvement of LVEDD, LVEDV, and 6MWT between the cell transplantation group and control groups. Subgroup analysis revealed that the intervention for control group could affect the efficacy of BMSC transplantation. Sensitivity analysis found the conclusion of LVEDD, LVEDV, and 6MWT changes was not stable. Therefore, among patients with IHD presenting HFrEF, BMSC transplantation during CABG is promising to be beneficial for postoperative left ventricular (LV) function improvement. However, according to the unstable results of the sensitivity analysis, it cannot be concluded whether the extra step has a positive effect on left ventricular remodeling and exercise capacity. RCTs with larger cohorts and more strict protocols are needed to validate these conclusions.

Differential expression of miRNAs from extracellular vesicles in chronic graft-versus-host disease: A preliminary study.

Chronic graft-versus-host disease (cGvHD) is a complex disorder that typically manifests after allogeneic hematopoietic stem cell transplantation (HSCT). It is a major cause of non-relapse mortality, which makes finding biomarkers associated with its occurrence a priority. Recent studies increasingly indicate that microRNAs (miRNAs, short regulatory RNA molecules) can be used as biomarkers of various disorders. They can circulate in patients' bodies encapsulated within extracellular vesicles (EVs). To identify miRNAs associated with the occurrence of cGvHD in EVs isolated from the plasma of patients after allogeneic HSCT. We performed global miRNA expression profiling in a pilot cohort of 3 cGvHD cases and 4 non-cGvHD patients without disease symptoms 90 days after the transplantation (control group). The 2 groups were naturally clustered according to their miRNA profiles using unsupervised hierarchical clustering analysis. We identified 3 miRNAs that were differentially expressed in the cGvHD patients compared to the non-cGvHD patients. The levels of hsa-miR-630 and hsa-miR-374b-5p were lower in the cGvHD patients: 4.1-fold (p = 0.002) and 2.7-fold (p = 0.044), respectively. In contrast, the levels of hsa-miR-29c-3p were 5.8-fold higher (p = 0.004). Our results suggest that miRNA profiles from plasma EVs may act as markers of cGvHD onset.

Survival Benefit of First Single-Organ Deceased Donor Kidney Transplantation Compared With Long-term Dialysis Across Ages in Transplant-Eligible Patients With Kidney Failure

Kidney transplant is considered beneficial in terms of survival compared with continued dialysis for patients with kidney failure. However, randomized clinical trials are infeasible, and available evidence from cohort studies is at high risk of bias. To compare restricted mean survival times (RMSTs) between patients who underwent transplant and patients continuing dialysis across transplant candidate ages and depending on waiting time, applying target trial emulation methods. In this retrospective cohort study, patients aged 18 years or older appearing on the wait list for their first single-organ deceased donor kidney transplant between January 1, 2000, and December 31, 2018, in Austria were evaluated. Available data were obtained from the Austrian Dialysis and Transplant Registry and Eurotransplant and included repeated updates on wait-listing status and relevant covariates. Data were analyzed between August 1, 2019, and December 23, 2021. A target trial was emulated in which patients were randomized to either receive the transplant immediately (treatment group) or to continue dialysis and never receive a transplant (control group) at each time an organ became available. The primary outcome was time from transplant allocation to death. Effect sizes in terms of RMSTs were obtained using a sequential Cox approach. Among the 4445 included patients (2974 men [66.9%]; mean [SD] age, 52.2 [13.2] years), transplant was associated with increased survival time across all considered ages compared with continuing dialysis and remaining on the wait list within a 10-year follow-up. The estimated RMST differences were 0.57 years (95% CI, -0.14 to 1.84 years) at age 20 years, 3.01 years (95% CI, 2.50 to 3.54 years) at age 60 years, and 2.48 years (95% CI, 1.88 to 3.04 years) at age 70 years. The survival benefit for patients who underwent transplant across ages was independent of waiting time. The findings of this study suggest that kidney transplant prolongs the survival time of persons with kidney failure across all candidate ages and waiting times.

Aspirin Reduces Ischemia-Reperfusion Injury Induced Endothelial Cell Damage of Arterial Grafts in a Rodent Model.

Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a nonsteroidal anti-inflammatory drug improves the long-term patency of vein grafts. Whether aspirin has the same effect on arterial grafts is questionable. We aimed to characterize the beneficial effects of aspirin on arterial bypass grafts in a rodent revascularization model. We gave Lewis rats oral pretreatment of either aspirin (n = 8) or saline (n = 8) for 5 days, then aortic arches were explanted and stored in cold preservation solution. The third group (n = 8) was a non-ischemia-reperfusion control. Afterwards the aortic arches were implanted into the abdominal aorta of recipient rats followed by 2 h of reperfusion. Endothelium-dependent vasorelaxation was examined with organ bath experiments. Immunohistochemical staining were carried out. Endothelium-dependent maximal vasorelaxation improved, nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the aspirin preconditioned group, compared to the transplanted control group. Significantly improved endothelial function and reduced I/R injury induced structural damage were observed in free arterial grafts after oral administration of aspirin. Aspirin preconditioning before elective CABG might be beneficial on free arterial graft patency.

The Effect of γ-secretase Inhibitor Combined with BMSC on the aGVHD in Mice Model

To establish the aGVHD mouse model，and investigate the regulatory effect and its mechanism of low-dose GSI combined with BMSC on aGVHD mice. C57BL/6 (H-2b) and BALB/c (H-2d) were selected as donor and recipient of allogeneic transplantation to establish the aGVHD mouse model. BALB/c mice were randomly divided into 6 groups, which were the bone marrow cell infusion after irradiation (BM) group; the bone marrow cells + spleen cells after irradiation (BM+SC) group; the bone marrow cells + spleen cells + DMSO (BM+SC+DMSO) (transplant control) group; bone marrow cells + splenocytes +GSI after irradiation (BM+SC+GSI) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal infusion after irradiation cell (BM+SC+BMSC) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal cells +GSI infused after irradiation (BM+SC+BMSC+GSI) group. The mice in the two groups containing GSI were intraperitoneally injected with GSI at 5 μmol/kg on day 1, 2, and 3 after transplantation with DMSO as a control. The general conditions, survival time and hematopoietic recovery of mice were observed, cytokines were detected by ELISA, and histopathological changes were detected by immunohistochemistry. The effects of low-dose GSI combined with BMSC on hematopoietic reconstruction and aGVHD development after allo-BMT were investigated. The survival rate of the mice in BM+SC+BMSC+GSI combination group was 80% during the observation period, which was significantly higher than that in the other groups; the incidence of aGVHD was reduced in the BMSC GSI or their combination groups after 21 days of transplantation. GSI could partly promote the recovery of leukocytes, and show no significant delayed effect on the recovery platelets. Moreover, the level of Th1 cytokines (IFN-γ) in BM+SC+BMSC+GSI combined group was lower than that in BM+SC+GSI group (P<0.01), the level of Th2 cytokines (IL-4) in the combination group was higher than that in BM+SC+GSI group (P<0.01), also the level of IL-17 was significantly lower than that in the corresponding control group (P<0.001). Low dose GSI combined with BMSC can promote hematopoietic reconstruction and regulate cytokines secretion including IFN-γ, IL-4 and IL-17. GSI combined with BMSC achieve the goal of synergistically inhibiting the occurrence and progression of aGVHD.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60mL/min/1.73m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p=.06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p=.027).

Pre-emptive immunosuppression using tacrolimus monotherapy does not reduce the rate of early acute rejection in renal transplantation from live donors: a comparative cohort study.

The planned nature of live donor kidney transplantation allows for immunosuppression to be initiated in the pretransplant period. The aim of this study was to determine the effect of pre-emptive immunosuppression on acute rejection rates after live donor kidney transplantation. In two consecutive cohorts of live donor kidneys transplants, 99 patients received pre-emptive immunosuppression with tacrolimus monotherapy for 2weeks prior to transplantation (PET group - first era) and 100 patients received tacrolimus-based immunosuppression commencing on the day of transplantation (control group - second era). The main outcome measure was the incidence of biopsy-proven acute rejection (BPAR) in the first 3months post-transplantation. Tacrolimus levels were significantly higher in the PET group at day 4 post-transplant (PET 9.08±4.57 vs. control 5.92±3.64ng/ml; P<0.0001), but there were no significant differences in tacrolimus levels at day 7 (PET 8.22±3.58 vs. control 7.63±3.56ng/ml; P=0.2452). BPAR was numerically higher in the PET group, but this difference did not reach statistical significance (PET 13/99 vs. control 6/100; P=0.097). There were no differences in allograft function measured by serum creatinine at 1year (PET 130±36 vs. control 142±69μmol/l; P=0.6829). Graft survival at 1year was equivalent in both groups (PET 96.9 vs. control 97.0%; P=0.9915). This study suggests that there is little role for the use of pre-emptive tacrolimus monotherapy in ABO blood group and HLA-compatible live donor kidney transplantation in patients on triple maintenance immunosuppression.

Role of T cell immune response cDNA 7 on the pathology of acute graft-versus-host disease.

Activation of T lymphocytes is the initiating factor of the occurrence of acute graft-versus-host disease (aGVHD), and cytotoxic T lymphocyte antigen-4 (CTLA-4) is the inhibitory receptor for activating T cells. T cell immune response cDNA 7 (TIRC7) is considered an upstream regulator of CTLA-4; however, little is understood regarding the effects of TIRC7 on the regulation of CTLA-4 in aGVHD. The purpose of the present study was to evaluate the regulatory effects of TIRC7 on aGVHD, mainly in the pathology. Recipient mice were exposed to a preconditioning dose of 7.5 Gy irradiation on the day of the transplantation and were divided into the following groups: Blank control group, bone marrow transplantation control group, total body irradiation group, mild-moderate aGVHD group and severe aGVHD group. According to the different administration of CTLA-4 and TIRC7 monoclonal antibodies, the mild-moderate and severe aGVHD groups were randomly divided into the hematopoietic stem cell transplantation (HSCT) and HSCT + CTLA-4/TIRC7 groups. Recipient mice were sacrificed at different time points post-HSCT for histopathological analysis by hematoxylin and eosin staining. Compared with the control and other experimental groups, the mice in the combined CTLA-4 and TIRC7 group exhibited ameliorated pathological injury, and lower pathology scores of the liver, lung and intestine. These data revealed that intraperitoneal injection of anti-TIRC7 and/or anti-CTLA-4 monoclonal antibody into mice could effectively alleviate the severity of aGVHD.

Study on Application of Bone Marrow Mesenchymal Stem Cells Transplantation in Restorative Treatment of Spinal Cord Injury in Mice

The spinal cord injury (SCI) refers to different degrees of injuries in the structure or function of spinal cord caused by different factors. The prevalence rate of SCI in the population under 40 years reaches 80%. SCI causes certain injury to both physiology and psychology of patients. An important factor leading to SCI is the rupture of nerve fibers. Bone marrow mesenchymal stem cells (BMMSCs) have the functions of inducing and supporting hematopoietic stem cells in bone marrow. In this study, SCI mouse model was established to assess the effect of BM-MSCs on SCI. A total of 30 SCI mouse model were established and assigned into transplantation group (15 mice) and control group (15 mice) according to random number table method. The mice in transplantation group were treated with BM-MSCs transplantation at SCI site, while mice in control group were treated with normal saline at SCI site. The bone marrow pathological changes were measured by HE staining and neural cells were assessed by Pischingert's methylene blue staining along with measuring SRY level by immunohistochemistry. The motor abilities of mice in transplantation group at the 2nd, 4th, 6th and 8th weeks were significantly higher than mice in control group (P &lt; 0 05). A few vacuoles appeared in mice in transplantation group. The number of cells in mouse spinal cord tissues in transplantation group was increased significantly over time, but a large number of vacuoles appeared in mouse spinal cord tissues in control group with necrosis of a vast amount of nerve fibers (P &lt; 0 05). The number and volume of Nissl bodies in mice in transplantation group was increased significantly at 2 weeks after treatment and degeneration status of nerve cells in transplantation group was significantly better than control group (P &lt; 0 05). The SRY genes were expressed in transplantation group for a long term but not in control group (P &lt; 0 05). The number of adherent cells increased significantly in transplantation group at 48 hours after treatment. BMMSCs transplantation can effectively promotes the recovery of SCI mice, indicating that it is worthy of clinical promotion and application.

Oncological and Postoperative Outcomes of Robot-Assisted Laparoscopic Radical Prostatectomy in Renal Transplant Recipients: A Multicenter and Comparative Study

BackgroundRobot-assisted laparoscopic radical prostatectomy (RARP) has been poorly studied in men with renal graft. ObjectiveTo determine the predictive factors for oncologic outcomes and complications after RARP in renal transplants recipients (RTRs). Design and ParticipantsA retrospective multicenter controlled study identified all RTRs who had undergone RARP between 2008 and 2016 in 2 experts departments. All RTRs were matched 1:1 with patients who had also undergone RARP but with no history of renal transplant (control group). InterventionRobot-assisted laparoscopic radical prostatectomy. Outcome MeasurementsIncontinence, oncologic outcomes, and complications according to the Clavien-Dindo classification. Statistical analysisComparisons of the quantitative variables using Student’s t tests, and comparisons of the qualitative variables using χ2 tests. Statistical analyses were performed using SAS (version 9.3). Independent risk factors of biochemical recurrence (BCR), postoperative complications, or incontinence were searched by using a multivariate linear regression. ResultsTwenty-seven RTRs were included in the transplant group and compared with 27 men in the control group with similar preoperative characteristics. Univariate analysis showed a shorter BCR-free survival in RTRs, with 26.9 months vs 49.3 months in the control group (P = .018). BCR rate was similar in each group (7.4% vs 11.1%, P = .639). No difference between groups was showed for immediate postoperative complications (29.6% vs 22.2%, P = .279). Multivariate analysis showed that a renal graft history was an independent risk factor of shorter BCR-free survival (hazard ratio = 4.291; 95% confidence interval, 2.102-8.761 and P < .001). Even if it is the first comparative study on this topic, the low number of men included is the main limitation of our study. ConclusionsThese findings show the reliability of RARP in RTRs. The rate of BCR does not appear more frequently but BCR-free survival seems shorter in these patients. A prospective comparative study remains necessary with more patients to confirm our results.

Serum iFGF-23, sKlotho, and 1,25 (OH)&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; D&amp;lt;sub&amp;gt;3&amp;lt;/sub&amp;gt; Vitamin Levels in Kidney Transplant

Aim of the study: Chronic kidney disease is characterized by elevated iFGF-23 level, which is known to regulate phosphate, little is known about the relationship between iFGF-23 and phosphate homeostasis in posttransplant patients, however. We will look at the iFGF-23 level and correlate it with sKlotho, and 1,25 (OH)₂ D₃ Vitamin in posttransplant patients. Material and methods: This study was conducted using 60 kidney transplant patients. 34 healthy subjects enrolled as a control group. Blood samples were withdrawn for measuring the levels of serum iFGF-23, sKlotho, 1,25 (OH)₂ D₃ Vitamin, Calcium, Phosphorus, iPTH, 25 (OH) D vitamin. CKD-EPI is used to calculate GFR. Results: iFGF-23 levels were elevated in the posttransplant period compared with healthy subjects. iFGF-23 levels were measured as 263.64±153.08 pg/ml in transplant patients and 155.05±73.40 pg/ml within the control group. sKlotho levels were measured as 2.82±1.76 ng/ml and 3.72±3.59 ng/ml in transplant patients and control groups respectively. 1,25 (OH)₂ D₃ Vitamin levels were measured as 49.56±13.73 pg/ml and 48.42±12.13 pg/ml in transplant patients and control group respectively. The results of this study revealed a significant correlation between iFGF-23 and sKlotho both in transplant patients and in the control group. Conclusions: Significantly elevated iFGF-23 and iPTH level accompanied by decreased GFR activity suggests a progressive deficiency in phosphate homeostasis.

Repair effect of bFGF combined with bone marrow mesenchymal stem cells on spinal cord injury in rats

To observe the repair effect of bone marrow mesenchymal stem cells (BMSCs) combined with basic fibroblast growth factor (bFGF) on spinal cord injury in rats and explore its mechanism. SD rat BMSCs were obtained by serum culture technique. Eighty healthy 6-week-old male SD rats(weight about 240 g) were randomly divided into 4 groups with 20 each. The sham operation group underwent simple laminectomy without damaging spinal cord and was kept in the same condition as the other 3 groups. The other 3 groups underwent left T9 spinal cord hemisection to establish spinal cord injury model. After 9 days of modeling the local transplantation was performed. The Control group was implanted with gelatin sponge containing normal saline. The BMSCs transplantation group was implanted with gelatin sponge containing BMSCs. The bFGF+BMSCs transplantation group was implanted with gelatin sponge containing bFGF+BMSCs. After 4 and 8 weeks, the expression of NF-200 and GFAP in injured spinal cord tissue was analyzed by Western blotting and the recovery of hind limb function was evaluated by Basso Beattie Bresnahan(BBB) motor function score scale. The BBB scores of BMSCs transplantation group and bFGF+BMSCs transplantation group were better than control group at 4 and 8 weeks after operation (P<0.05) and there was significant difference between bFGF+BMSCs transplantation group and BMSCs transplantation group (P<0.05). After 4 and 8 weeks postoperatively, NF-200 expression was minimal in control group and only a small amount was expressed in BMSCs transplantation group while in bFGF+BMSCs transplantation group NF-200 was highly expressed(P<0.05). GFAP expression was high in control group, middle in BMSCs transplantation group and low in bFGF BMSCs transplantation group(P<0.05). There was significant difference between bFGF+BMSCs transplantation group, BMSCs transplantation group and control group(P<0.05). The combined transplantation of BMSCs and bFGF can repair the spinal cord injury in rats. The mechanism may be related to the decrease of GFAP expression and the increase of NF-200 expression.

Stem cells purified from human induced pluripotent stem cell-derived neural crest-like cells promote peripheral nerve regeneration

Strategies for therapeutic cell transplantation have been assessed for use in the treatment of massive peripheral nerve defects. To support safe and efficient cell transplantation, we have focused on the purification of cells using cell surface markers. Our group previously reported low-affinity nerve growth factor receptor (LNGFR)- and thymocyte antigen-1 (THY-1)-positive neural crest-like cells (LT-NCLCs), generated from human induced pluripotent stem cells (hiPSCs). In the present study, we investigated the efficacy of transplantation of hiPSC-derived LT-NCLCs in a murine massive peripheral nerve defect model. Animals with a sciatic nerve defect were treated with a bridging silicone tube prefilled with LT-NCLCs or medium in the transplantation (TP) and negative control (NC) groups, respectively. The grafted LT-NCLCs survived and enhanced myelination and angiogenesis, as compared to the NC group. Behavioral analysis indicated that motor functional recovery in the TP group was superior to that in the NC group, and similar to that in the autograft (Auto) group. LT-NCLCs promoted axonal regrowth and remyelination by Schwann cells. Transplantation of LT-NCLCs is a promising approach for nerve regeneration treatment of massive peripheral nerve defects.

Shear Wave Elastography Findings of Achilles Tendons in Patients on Chronic Hemodialysis and Patients with renal Transplantation

Introduction Achilles tendon which was comprised of tendinous parts of gastrocnemius and soleus muscles is the strongest and the largest tendon in the human body. Chronic renal disease is related to reduced physical activity, exercise capacity. Spontaneous rupture of achilles tendon have been reported in patients with chronic renal disease and degeneratif changes, recurrent microtraumas, hypoxia, chronic acidosis are predisposing factors. The aim of the study is to assess the degeneration of achilles tendon by shear wave elastography to compare the elastographic findings of Achilles tendons in patients on chronic hemodialysis, patients with renal transplantation and healthy adults. Materials and Methods Twenty-five patients who were on chronic hemodialysis at least 5 years, twenty-five renal transplant patients and twenty-five healthy controls were included in this study. The thickness and shear wave velocity (SWV) of the middle thirds of the achilles tendons were measured bilaterally. Results The mean SWV of right achilles was 3,67 cm/sn left achilles was 3,64 cm/sn in hemodialysis group. The mean SWV of right achilles was 4,29 cm/sn left achilles was 4,25 cm/sn in renal transplant group. The mean SWV of right achilles was 6,68 cm/sn left achilles was 6,59 cm/sn in control group. There was a statistically significant difference between the SWVs of hemodialysis group, renal transplant group and control group (p<0,005). Conclusion The achilles tendons in patients with chronic renal failure were softer than in patients with renal transplantation and control group. Chronic tendinopathy cause softening and weakening of the tendon. In the renal transplant group stiffness of the achilles tendon was increased with respect to hemodialysis group but still softer than the control group which could be explained by the positive clinical effect of renal transplantation. In conclusion shear wave elastography is an objective, easy, noninvasive, method that can asssess tendinopathy.

The prevalence of HLA alleles in a lupus nephritis population

BackgroundSystemic lupus erythematosus (SLE) is a severe autoimmune disease that involves multiple organ systems. Lupus nephritis (LN) is a complication of SLE and is associated with poor survival and high morbidity. Many genomic studies have been performed worldwide, and several histocompatibility leukocyte antigen (HLA) loci are linked to lupus susceptibility. ObjectiveThe present study evaluated the association of HLA alleles in a lupus patient population, LN group and control group. The second objective evaluated whether HLA allele match or mismatch influenced kidney graft survival in a kidney transplanted lupus population. MethodsThis study was a retrospective study of 2 major groups: general lupus patients (GSLE - n = 108) and a control group (GControl - n = 216). Both groups were also divided into subgroups. ResultsThe control group was divided into two subgroups: a healthy control group (HeCTRL) and transplant control group (TxCTRL). The GSLE group was composed of transplanted lupus patients (TxSLE) and non-transplanted lupus patients (nTxSLE). Comparison of the demographics between groups did not reveal differences between ethnicity and gender. A difference in the prevalence of three alleles, B*08, DRB1*08 and DRB1*15, was observed. These alleles were more prevalent in the lupus subgroups compared to the control groups. Five-year survival was not different between patients carrying the allele DRB1*15 in either group (overall p = 0.075; TxSLE p = 0.419; TxCTRL = 0.309). The presence of the match with this allele in the receptor was evaluated and did not demonstrate any difference in graft survival in both groups (p = 0.146) or when analyzed separately in each group (TxCTRL p = 0.739; TxSLE = 0.297). ConclusionThis study demonstrated that the presence of HLA-DRB1*15 was a strong factor that predisposed patients to the development of SLE and LN, but did not influence kidney graft survival.

Does Renal Tubular Injury–Induced Local Tissue Hypoxia Involve Post-Transplantation Erythrocytosis?

BackgroundThe pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE. MethodsThis cross-sectional study included 15 renal transplant recipients, in whom polycythemia developed after kidney transplantation, with elevated hematocrit level to >51%. Forty-eight age- and gender-matched renal transplant recipients with normal hematocrit level were included as the renal transplant control group. In addition, 13 age- and gender-matched healthy subjects were also included as the healthy control group. We used urine hypoxia-inducible factor-2 alpha (HIF-2α) levels to evaluate whether there is local tissue hypoxia in renal allograft. HIF-2α levels were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). Serum EPO and insulin-like growth factor-1 (IGF-1) levels were also measured. ResultsHIF-2α levels were significantly lower in the polycythemia group than the other two groups, but there was no significant difference between the healthy control group and the renal transplant control group with regard to HIF-2α levels. There was no significant difference among the 3 study groups in terms of levels of serum EPO and IGF-1. ConclusionLocal tissue hypoxia in renal allograft does not seem to play an important role in the development of PTE.

Transplantation of Human Dental Pulp-Derived Stem Cells or Differentiated Neuronal Cells from Human Dental Pulp-Derived Stem Cells Identically Enhances Regeneration of the Injured Peripheral Nerve.

Human dental mesenchymal stem cells isolated from the dental follicle, pulp, and root apical papilla of extracted wisdom teeth have been known to exhibit successful and potent neurogenic differentiation capacity. In particular, human dental pulp-derived stem cells (hDPSCs) stand out as the most prominent source for in vitro neuronal differentiation. In this study, to evaluate the in vivo peripheral nerve regeneration potential of hDPSCs and differentiated neuronal cells from DPSCs (DF-DPSCs), a total of 1 × 106 hDPSCs or DF-hDPSCs labeled with PKH26 tracking dye and supplemented with fibrin glue scaffold and collagen tubulization were transplanted into the sciatic nerve resection (5-mm gap) of rat models. At 12 weeks after cell transplantation, both hDPSC and DF-hDPSC groups showed notably increased behavioral activities and higher muscle contraction forces compared with those in the non-cell transplanted control group. In immunohistochemical analysis of regenerated nerve specimens, specific markers for angiogenesis, axonal fiber, and myelin sheath increased in both the cell transplantation groups. Pretransplanted labeled PKH26 were also distinctly detected in the regenerated nerve tissues, indicating that transplanted cells were well-preserved and differentiated into nerve cells. Furthermore, no difference was observed in the nerve regeneration potential between the hDPSC and DF-hDPSC transplanted groups. These results demonstrate that dental pulp tissue is an excellent stem cell source for nerve regeneration, and in vivo transplantation of the undifferentiated hDPSCs could exhibit sufficient and excellent peripheral nerve regeneration potential.