Donor-containing cortical and intraventricular glioneuronal nodules in Huntington's disease brain decades after fetal cell transplantation.
Ontology highlight
ABSTRACT:
SUBMITTER: Pinarbasi ES
PROVIDER: S-EPMC8119370 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
Donor-containing cortical and intraventricular glioneuronal nodules in Huntington's disease brain decades after fetal cell transplantation.
Pinarbasi Emile S ES Liu Elaine A EA Yu Zhigang Z Kopyov Oleg O Brown Noah A NA Dayalu Praveen P Lieberman Andrew P AP
Acta neuropathologica 20210308 6
Similar Datasets
Project description:Four decades ago, Broxmeyer et al. demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al. reported the first successful matched sibling cord blood transplant (CBT) in a child with Fanconi Anemia. In 1991, Rubinstein et al. established an unrelated donor CB bank, and in 1993, the first unrelated CBT used a unit from this bank. Since that time, >40 000 CBTs have been performed worldwide. Early outcomes of CBT were mixed and demonstrated the importance of cell dose from the CB donor. We hypothesized that improvements in CB banking and transplantation favorably impacted outcomes of CBT today and performed a retrospective study combining data from Eurocord and Duke University in 4834 children transplanted with a single unrelated CB unit (CBU) from 1993 to 2019. Changes in standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic graft-versus-host disease [GvHD], treatment related mortality [TRM], and relapse) over 3 time periods (1: <2005; 2: 2005 to <2010; and 3: >2010 to 2019) were studied. Increased cell dose and degree of HLA matching were observed over time. OS, times to engraftment, and DFS improved over time. The incidence of TRM and GvHD decreased while the incidence of relapse remained unchanged. Relative contributions of cell dose and HLA matching to transplant outcomes were also assessed and showed that HLA matching was more important than cell dose in this pediatric cohort.
| S-EPMC9887081 | biostudies-literature
Project description:After allogeneic hematopoietic cell transplantation (HCT), a very small number of donor stem cells reconstitute the recipient hematopoietic system, whereas the donor is left with a near-normal pool of stem cells. We hypothesized that the increased replicative stress on transplanted donor cells in the recipient could lead to the disproportionate proliferation of clonal hematopoiesis (CH) variants. We obtained blood samples from 16 related donor-recipient pairs at a median of 33.8 years (range: 6.6 to 45.7) after HCT, including the longest surviving HCT recipients in the world. For 11 of 16 pairs, a donor sample from the time of HCT was available for comparison. We performed ultrasensitive duplex sequencing of genes recurrently mutated in myeloid malignancies and CH, as well as a set of functionally neutral genomic regions representative of human genomic content at large. CH variants were observed in all donors, even those as young as 12 years old. Where donor pre-HCT sample was available, the average mutation rate in donors compared to recipients post-HCT was similar (2.0% versus 2.6% per year, respectively) within genes recurrently mutated in myeloid malignancies. Twenty-two (5.6%) of the 393 variants shared between paired donors and recipients post-HCT showed ≥10-fold higher variant allele frequency (VAF) in the recipient. A longer time since HCT was positively associated with the expansion of shared variant VAFs in the recipient. In conclusion, even decades after HCT, there does not appear to be widespread accelerated clonal expansion in the transplanted cells, highlighting the immense regenerative capacity of the human hematopoietic system.
| S-EPMC11813252 | biostudies-literature
Project description:Huntington's disease (HD) is a devastating neurogenetic disorder whose familial nature and progressive course were first described in the 19th century but for which no disease-modifying treatment is yet available. Through the active participation of HD families, this disorder has acted as a flagship for the application of human molecular genetic strategies to identify disease genes, understand pathogenesis and identify rational targets for development of therapies.
| S-EPMC8490011 | biostudies-literature
Project description:Background and aimsLiver organ shortage remains a major health burden in the US, with more patients being waitlisted than the number of liver transplants (LTs) performed. This study investigated US national and regional trends in living donor LT (LDLT) and identified factors associated with recipient survival.MethodsWe retrospectively analyzed LDLT recipients and donors from the United Network Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics, demographic differences, and survival rate. National and regional trends in LDLT, recipient outcomes, and predictors of survival were analyzed.ResultsOf the 223,571 candidates listed for an LT, 57.5% received an organ, of which only 4.2% were LDLTs. Annual adult LDLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by 2009. LDLTs then gradually increased to 445 in 2019. Region 2 had the highest LDLT numbers (n=919), while region 1 had the highest proportion (11.1%). Overall, post-LT mortality was 21.4% among LDLT recipients. Post-LDLT survival rates after 1-, 5-, and 10-years were 92%, 87%, and 70%, respectively. Interval analysis (2004-2019) showed that patients undergoing LDLT in recent years had lower mortality than in earlier years (hazard ratio=0.81, 95% confidence interval=0.75-0.88).ConclusionsFollowing a substantial decline after a peak in 2001, the number of adult LDLTs steadily increased from 2011 to 2019. However, LDLTs still constitute the minority of the transplant pool in the US. Life-saving policies to increase the use of LDLTs, particularly in regions of high organ demand, should be implemented.
| S-EPMC9547266 | biostudies-literature
Project description:The introduction of living donor liver transplantation (LDLT) has been one of the most remarkable steps in the field of liver transplantation (LT). First introduced for children in 1989, its adoption for adults has followed only 10 years later. As the demand for LT continues to increase, LDLT provides life-saving therapy for many patients who would otherwise die awaiting a cadaveric organ. In recent years, LDLT has been shown to be a clinically safe addition to deceased donor liver transplantation (DDLT) and has been able to significantly extend the scarce donor pool. As long as the donor shortage continues to increase, LDLT will play an important role in the future of LT.
| S-EPMC2131378 | biostudies-other
Project description:Purpose: We are aiming to build a supervised machine learning-based classifier, in order to preoperatively distinguish focal cortical dysplasia (FCD) from glioneuronal tumors (GNTs) in patients with epilepsy. Methods: This retrospective study was comprised of 96 patients who underwent epilepsy surgery, with the final neuropathologic diagnosis of either an FCD or GNTs. Seven classical machine learning algorithms (i.e., Random Forest, SVM, Decision Tree, Logistic Regression, XGBoost, LightGBM, and CatBoost) were employed and trained by our dataset to get the classification model. Ten features [i.e., Gender, Past history, Age at seizure onset, Course of disease, Seizure type, Seizure frequency, Scalp EEG biomarkers, MRI features, Lesion location, Number of antiepileptic drug (AEDs)] were analyzed in our study. Results: We enrolled 56 patients with FCD and 40 patients with GNTs, which included 29 with gangliogliomas (GGs) and 11 with dysembryoplasic neuroepithelial tumors (DNTs). Our study demonstrated that the Random Forest-based machine learning model offered the best predictive performance on distinguishing the diagnosis of FCD from GNTs, with an F1-score of 0.9180 and AUC value of 0.9340. Furthermore, the most discriminative factor between FCD and GNTs was the feature "age at seizure onset" with the Chi-square value of 1,213.0, suggesting that patients who had a younger age at seizure onset were more likely to be diagnosed as FCD. Conclusion: The Random Forest-based machine learning classifier can accurately differentiate FCD from GNTs in patients with epilepsy before surgery. This might lead to improved clinician confidence in appropriate surgical planning and treatment outcomes.
| S-EPMC7732488 | biostudies-literature
Project description:BACKGROUND:The expression of the HTT CAG repeat expansion mutation causes neurodegeneration in Huntington's disease (HD). OBJECTIVES:In light of the - mainly in-vitro - evidence suggesting an additional role of huntingtin in neurodevelopment we used 3T MRI to test the hypothesis that in CAG-expanded individuals without clinical signs of HD (preHD) there is evidence for neurodevelopmental abnormalities. METHODS:We specifically investigated the complexity of cortical folding, a measure of cortical neurodevelopment, employing a novel method to quantify local fractal dimension (FD) measures that uses spherical harmonic reconstructions. RESULTS:The complexity of cortical folding differed at a group level between preHD (n = 57) and healthy volunteers (n = 57) in areas of the motor and visual system as well as temporal cortical areas. However, there was no association between the complexity of cortical folding and the loss in putamen volume that was clearly evident in preHD. CONCLUSIONS:Our results suggest that HTT CAG repeat length may have an influence on cortical folding without evidence that this leads to developmental pathology or was clinically meaningful. This suggests that the HTT CAG-repeat expansion mutation may influence the processes governing cortical neurodevelopment; however, that influence seems independent of the events that lead to neurodegeneration.
| S-EPMC6627026 | biostudies-literature
Project description:Potter sequence consists of various symptoms associated with renal dysplasia. For bilateral renal agenesis, there is no hope of survival. As a novel therapeutic approach for Potter sequence, we develop a unique approach of "transplantation of fetal kidneys from a different species during the fetal stage." In this study, we first validate the approach using allogeneic transplantation. Fetal kidneys with bladders from green fluorescent protein-expressing rats (embryonic day 14.0-16.5) are subcutaneously transplanted into allogeneic rat fetuses in utero (embryonic day 18.0-18.5). After birth, the transplanted fetal kidneys are confirmed to have urine production capability. Furthermore, long-term (up to 150 days) urine production is sustained. Next, we perform xenotransplantation. The transplantation of mouse fetal kidneys into rat fetuses in utero leads to the maturation of renal tissue structures. We demonstrate organ transplantation into in utero fetuses using fetal kidneys as donor organs for fetal therapy.
| S-EPMC11876676 | biostudies-literature
Project description:There are now more than 25 million volunteer donors registered worldwide for patients in need of a life-saving hematopoietic cell transplant to cure blood disorders. Although a human leukocyte antigen (HLA)-matched donor remains the preferred stem cell source for transplantation, the use of a donor with limited HLA mismatching may be considered. Significant advances in clinical and basic research have been instrumental in furthering the understanding of donor-recipient HLA mismatches that are better tolerated than other mismatches. An increased appreciation of the role of regulatory region variation that affects the level of HLA expression provides new approaches for the selection of HLA-mismatched donors.
| S-EPMC5101019 | biostudies-literature
Project description:Human fetal gonads acquire endocrine steroidogenic capabilities early during their differentiation. Genetic studies show that this endocrine function plays a central role in the sexually dimorphic development of the external genitalia during fetal development. When this endocrine function is dysregulated, congenital malformations and pathologies are the result. In this review, we explain how the current knowledge of steroidogenesis in human fetal gonads has benefited from both the technological advances in steroid measurements and the assembly of detailed knowledge of steroidogenesis machinery and its expression in human fetal gonads. We summarise how the conversion of radiolabelled steroid precursors, antibody-based assays, mass spectrometry, ultrastructural studies, and the in situ labelling of proteins and mRNA have all provided complementary information. In this review, our discussion goes beyond the debate on recommendations concerning the best choice between the different available technologies, and their degrees of reproducibility and sensitivity. The available technologies and techniques can be used for different purposes and, as long as all quality controls are rigorously employed, the question is how to maximise the generation of robust, reproducible data on steroid hormones and their crucial roles in human fetal development and subsequent functions.
| S-EPMC8268622 | biostudies-literature