Aberrant and Ectopic Cell Populations of the Fibrotic Front of Restrictive Allograft Syndrome after Lung Transplantation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE284081 | GEO | 2026/03/24
REPOSITORIES: GEO
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Project description:Aberrant and Ectopic Cell Populations of the Fibrotic Front of Restrictive Allograft Syndrome after Lung Transplantation
| PRJNA1196966 | ENA
Project description:Single-nuclei RNA-sequencing (snRNA-seq) using the 10x Genomics Flex technology was performed in peripheral lung tissues from PPFE patients undergoing lung re-transplantation, and from healthy control lungs.
2026-03-24 | GSE301982 | GEO
Project description:KL-6 is an antigen produced mainly by damaged type II pneumocytes that is involved in interstitial lung disease. Chronic lung allograft dysfunction (CLAD) after lung transplantation (LT) is a major concern for LT clinicians, especially in patients with restrictive allograft syndrome (RAS). We investigated KL-6 levels in serum and bronchoalveolar lavage fluid (BALF) as a potential biomarker of the RAS phenotype. Levels of KL-6 in serum and BALF were measured in 73 bilateral LT recipients, and patients were categorized into 4 groups: stable (ST), infection (LTI), bronchiolitis obliterans syndrome (BOS), and RAS. We also studied a healthy cohort to determine reference values for serum KL-6. The highest levels of KL-6 were found in the serum of patients with RAS (918 [487.8-1638] U/mL). No differences were found for levels of KL-6 in BALF. Using a cut-off value of 465 U/mL serum KL-6 levels was able to differentiate RAS patients from BOS patients with a sensitivity of 100% and a specificity of 75%. Furthermore, higher serum KL-6 levels were associated with a decline in Forced Vital Capacity (FVC) at 6 months after sample collection. Therefore, KL-6 in serum may well be a potential biomarker for differentiating between the BOS and RAS phenotypes of CLAD in LT recipients.
| S-EPMC6957146 | biostudies-literature
Project description:Surgical strategies for knee joint preservation are numerous, with the procedure(s) of choice for a given patient dependent on the status of the articular cartilage, meniscus, overall alignment, and ligamentous stability. For patients with large, isolated, osteochondral defects of the articular cartilage of the femoral condyle, osteochondral allograft transplantation (OCA) is often performed in an effort to reduce pain and improve function. Similarly, for appropriately indicated patients with symptomatic meniscus deficiency, meniscus allograft transplantation (MAT) is an excellent surgical solution. Often patients require concomitant MAT and OCA as part of a joint preservation strategy. In this Technical Note, we describe the surgical technique for performing arthroscopic-assisted concomitant lateral MAT and lateral femoral condyle OCA as part of a knee joint preservation strategy.
| S-EPMC5710720 | biostudies-literature
Project description:BackgroundLong-term survival after lung transplantation remains limited by chronic lung allograft dysfunction (CLAD). CLAD has 2 histologic phenotypes, namely obliterative bronchiolitis (OB) and restrictive alveolar fibroelastosis (AFE), which have distinct clinical presentations, pathologies, and outcomes. Understanding of OB versus AFE pathogenesis would improve with better animal models.MethodsWe utilized a ferret orthotopic single-lung transplantation model to characterize allograft fibrosis as a histologic measure of CLAD. Native lobes and "No CLAD" allografts lacking aberrant histology were used as controls. We used morphometric analysis to evaluate the size and abundance of B-cell aggregates and tertiary lymphoid organs (TLOs) and their cell composition. Quantitative RNA expression of 47 target genes was performed simultaneously using a custom QuantiGene Plex Assay.ResultsFerret lung allografts develop the full spectrum of human CLAD histology including OB and AFE subtypes. While both OB and AFE allografts developed TLOs, TLO size and number were greater with AFE histology. More activated germinal center cells marked by B-cell lymphoma 6 Transcription Repressor, (B-cell lymphoma 6) expression and fewer cells expressing forkhead box P3 correlated with AFE, congruent with greater diffuse immunoglobulin, plasma cell abundance, and complement 4d staining. Furthermore, forkhead box P3 RNA induction was significant in OB allografts specifically. RNA expression changes were seen in native lobes of animals with AFE but not OB when compared with No CLAD native lobes.ConclusionsThe orthotopic ferret single-lung transplant model provides unique opportunities to better understand factors that dispose allografts to OB versus AFE. This will help develop potential immunomodulatory therapies and antifibrotic approaches for lung transplant patients.
| S-EPMC9529760 | biostudies-literature
Project description:BackgroundChronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described.MethodsLT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis.ResultsAmong patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS.ConclusionAlthough these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.
| S-EPMC5511826 | biostudies-literature
Project description:Meniscal tears treated with partial meniscectomies have been shown to significantly increase contract pressures within the tibiofemoral joint, and a complete focal meniscal deficiency may render the entirety of the meniscus functionally incompetent. Although various techniques of meniscal transplantation have been described, these techniques may require the excision of a considerable amount of healthy meniscal tissue. Furthermore, failures continue to frequently occur. Therefore, attempts to restoring normal knee kinematics and biomechanical forces are essential. Segmental meniscus allograft transplantations may offer the advantage of a robust repair by both maintaining knee biomechanics and biology while maximizing preservation of native meniscal tissue. Also, most meniscal deficiency involves only a portion of the meniscus, and thus we developed this technique to segmentally transplant only the deficient portion. The purpose of this Technical Note is to describe a technique of segmental medial meniscus allograft transplantation in a patient with focal medial meniscus deficiency.
| S-EPMC7953169 | biostudies-literature
Project description:Chondral defects of the patellofemoral joint remain a difficult-to-treat pathology with limited long-term results. Currently available techniques to treat large or unipolar chondral defects of the patella include autologous chondrocyte implantation and osteochondral allograft transplantation. Despite the recent advances in orthobiologic adjuncts, there is no single gold-standard surgical approach to this difficult-to-treat pathology in patients who are frequently young, active, and demanding on their bodies. We describe a technique for osteochondral allograft transplantation to the patella for an isolated patellar chondral lesion (unipolar).
| S-EPMC6823814 | biostudies-literature
Project description:IntroductionWe performed a survivorship analysis of patients treated with patellofemoral osteochondral allograft transplantation (OCA) using either a shell or plug technique and identified variables associated with graft failure.MethodsConsecutive patients at two institutions who underwent OCA of the patellofemoral compartment between March 1, 2001 to March 1, 2015, were retrospectively identified at minimum 2 years' follow-up. Demographic information, intraoperative findings, and postoperative data were collected. Patients were divided into two groups on the basis of surgical technique (plug group and shell group). Failure was defined as revision OCA, conversion to arthroplasty, or gross appearance of graft degeneration on second-look arthroscopy. Logistic regression analysis was performed to identify patient- and surgery-specific variables associated with survivorship.ResultsFifty patients were identified (36 women and 14 men; mean age 37.43 ± 8.87 years). Sixteen patients received plug allografts, whereas 34 received shell allografts. Forty percent of patients underwent a concomitant meniscal, ligamentous, malalignment, or chondral procedure. Five patients in the Plug Group (31.3%) underwent reoperation at a mean 1.37 ± 1.34 years, and 28 patients (82.4%) who received Shell OCA underwent reoperation at a mean 1.94 ± 1.92 years. Two patients in the plug group had graft failure at a mean 9.17 ± 0.93 years, whereas 13 patients in the shell group had graft failure at a mean 3.81 ± 2.78 years. Patients with plug allografts demonstrated 100% and 66% survival at 5 and 9.8 years, respectively. For the shell group, survivorship was 65.8% and 37% at 5 and 10.6 years, respectively. Increasing body mass index was associated with failure for the case series overall (odds ratio 1.33, P = .020). Traumatic cause was found to be protective of failure (odds ratio = 0.02, P = .035).ConclusionsPlug OCA of the patellofemoral compartment can be an efficacious procedure with quality mid-term outcomes. Shell OCA led to high failure rates at midterm outcomes. Increasing body mass index may predispose patients to failure, whereas traumatic cause of their lesion was associated with improved outcomes.Level of evidenceLevel IV, Therapeutic case series.
| S-EPMC7120803 | biostudies-literature
Project description:Osteochondral allograft transplantation is a useful technique to manage larger articular cartilage injuries. One factor that may compromise the effectiveness of this procedure is chondrocyte cell death that occurs during the storage, preparation, and implantation of the osteochondral grafts. Loss of viable chondrocytes may negatively affect osteochondral edge integration and long-term function. A better understanding of the mechanisms responsible for chondrocyte loss could lead to interventions designed to decrease cell death and improve results. Recent studies indicate that apoptosis, or programmed cell death, is responsible for much of the chondrocyte death associated with osteochondral allograft transplantation. Theoretically, some of these cells can be rescued by blocking important apoptotic mediators. We review the role of apoptosis in cartilage degeneration, focusing on apoptosis associated with osteochondral transplantation. We also review the pathways thought to be responsible for regulating chondrocyte apoptosis, as well as experiments testing inhibitors of the apoptotic pathway. These data suggest that key contributors to the apoptotic process can be manipulated to enhance chondrocyte survival. This knowledge may lead to better surgical outcomes for osteochondral transplantation.
| S-EPMC2584268 | biostudies-other