Cell Transplantation最新文献

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Salvage nintedanib plus low-dose ruxolitinib therapy for bronchiolitis obliterans syndrome refractory to calcineurin inhibitors and glucocorticoids after allogeneic transplantation. 挽救尼达尼加小剂量鲁索利替尼治疗异基因移植后钙调磷酸酶抑制剂和糖皮质激素难治性闭塞性细支气管炎综合征。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2026-01-01 Epub Date: 2026-04-03 DOI: 10.1177/09636897261438731
Ya Luo, Ying Wu, Qiu-Sha Huang, Xian-Ying Yin, Qian-Nan Shang, Yi-Han Yang, Ao-Ran Zhang, Tong Su, Xiao-Han Su, Su-Xuan Liu, Zheng-Li Xu, Jing Liu, Xiao-Dong Mo, Yu-Qian Sun, Yu Wang, Meng Lv
{"title":"Salvage nintedanib plus low-dose ruxolitinib therapy for bronchiolitis obliterans syndrome refractory to calcineurin inhibitors and glucocorticoids after allogeneic transplantation.","authors":"Ya Luo, Ying Wu, Qiu-Sha Huang, Xian-Ying Yin, Qian-Nan Shang, Yi-Han Yang, Ao-Ran Zhang, Tong Su, Xiao-Han Su, Su-Xuan Liu, Zheng-Li Xu, Jing Liu, Xiao-Dong Mo, Yu-Qian Sun, Yu Wang, Meng Lv","doi":"10.1177/09636897261438731","DOIUrl":"10.1177/09636897261438731","url":null,"abstract":"<p><p>Bronchiolitis obliterans syndrome (BOS) is a severe pulmonary complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with limited therapeutic options once refractory to standard immunosuppression. We conducted a pilot study from January 2018 to December 2024, enrolling consecutive patients with BOS defined by NIH criteria who failed glucocorticoids and calcineurin inhibitors for ≥4 weeks. Sixteen patients received salvage therapy with ruxolitinib 5 mg twice daily and nintedanib 150 mg twice daily (RN cohort) in continuous 28-day cycles for up to six cycles, while 37 contemporary patients served as controls. At baseline, NIH lung scores in the RN cohort were 18.8% NIH 1, 18.8% NIH 2, and 62.5% NIH 3. The median number of treatment cycles was 3.5 (range, 1-6). At 3 months, 11 patients (68.8%) achieved ≥10% improvement in %FEV1 from baseline (median = 26.5%, range = 15.6%-58.2%). By NIH lung response criteria, the overall response rate (ORR) was 62.5% (12.5% complete response, 50.0% partial response) in the RN cohort versus 13.5% (5.4% complete, 8.1% partial) in controls. Notably, hematologic toxicities were less frequent with RN therapy than in controls. These findings suggest that low-dose ruxolitinib combined with nintedanib is an effective and well-tolerated salvage regimen for BOS after allo-HSCT and warrant confirmation in a prospective phase II study.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261438731"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Imaging-based tracking of stem-cell responses for 3D bioprinting optimization. 3D生物打印优化中基于成像的干细胞反应跟踪。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2026-01-01 Epub Date: 2026-05-25 DOI: 10.1177/09636897261445006
Bohdan Karabinskyi, Svitlana Alkhimova, Olena Holembiovska
{"title":"Imaging-based tracking of stem-cell responses for 3D bioprinting optimization.","authors":"Bohdan Karabinskyi, Svitlana Alkhimova, Olena Holembiovska","doi":"10.1177/09636897261445006","DOIUrl":"10.1177/09636897261445006","url":null,"abstract":"<p><p>This review examines how mechanical and chemical stimuli shape stem-cell behavior and how live-cell imaging combined with artificial intelligence can support the evaluation and optimization of 3D bioprinting workflows. Current evidence indicates that substrate stiffness, stretch, shear stress, compression, and soluble factors such as transforming growth factor beta (TGF-β), bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2) influence viability, migration, morphology, and lineage commitment in biopolymeric constructs. Imaging modalities including phase-contrast, fluorescence, confocal, two-photon, and light-sheet microscopy enable dynamic observation of these responses, while computational pipelines for segmentation, tracking, and feature extraction improve scalability and reproducibility of analysis. Across the reviewed studies, image-derived readouts such as cell distribution, motility, adhesion patterns, and early morphological changes emerge as promising indicators of construct quality and maturation potential. At the same time, broader application remains limited by phototoxicity, imaging depth constraints, data-processing demands, incomplete standardization of metrics, and restricted model generalizability. Overall, imaging-based cell tracking integrated with AI-assisted analysis offers a practical framework for post-print evaluation and iterative optimization in 3D bioprinting, with potential to strengthen quality control, reproducibility, and biological interpretation in regenerative engineering.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261445006"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of the efficacy and survival of allogeneic hematopoietic stem cell transplantation and nontransplantation treatment in chronic active Epstein-Barr virus infection. 异基因造血干细胞移植与非移植治疗慢性活动性eb病毒感染的疗效及生存率分析。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2026-01-01 Epub Date: 2026-05-30 DOI: 10.1177/09636897261443609
Xi Ming, Xiaoying Zhang, Jiaying Wu, Wanying Liu, Qi Zhang, Delian Zhou, Yicheng Zhang, Xiaojian Zhu, Yi Xiao
{"title":"Analysis of the efficacy and survival of allogeneic hematopoietic stem cell transplantation and nontransplantation treatment in chronic active Epstein-Barr virus infection.","authors":"Xi Ming, Xiaoying Zhang, Jiaying Wu, Wanying Liu, Qi Zhang, Delian Zhou, Yicheng Zhang, Xiaojian Zhu, Yi Xiao","doi":"10.1177/09636897261443609","DOIUrl":"10.1177/09636897261443609","url":null,"abstract":"<p><p>This retrospective study evaluated 75 patients with chronic active Epstein-Barr virus infection (CAEBV) to compare the efficacy and survival outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) and programmed death-1 (PD-1) blockade therapy. Patients were classified into HSCT and non-HSCT groups. The primary endpoints were overall response rate (ORR), overall survival (OS), and event-free survival (EFS). HSCT significantly improved ORR, 3-year OS, and 3-year EFS compared to non-HSCT treatment. Subgroup analysis showed that PD-1 blockade achieved outcomes comparable to HSCT in a subset of patients; however, HSCT remained superior, overall, particularly in patients without hemophagocytic lymphohistiocytosis (HLH). The presence of HLH was identified as an independent risk factor for inferior survival. In conclusion, allogeneic HSCT remains the preferred curative strategy for CAEBV, whereas PD-1 blockade represents a promising alternative for carefully selected patients. Early recognition and management of HLH are crucial for improving prognosis.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261443609"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Donor-specific immunomodulation is mediated by mechanisms beyond CD4+ regulatory T cells. 供体特异性免疫调节是由CD4+调节性T细胞以外的机制介导的。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2026-01-01 Epub Date: 2026-08-03 DOI: 10.1177/09636897261473440
Makiko Kumagai-Braesch, Nils Ågren, Masaaki Watanabe, Bo-Göran Ericzon, Michael Uhlin, Ming Yao
{"title":"Donor-specific immunomodulation is mediated by mechanisms beyond CD4<sup>+</sup> regulatory T cells.","authors":"Makiko Kumagai-Braesch, Nils Ågren, Masaaki Watanabe, Bo-Göran Ericzon, Michael Uhlin, Ming Yao","doi":"10.1177/09636897261473440","DOIUrl":"10.1177/09636897261473440","url":null,"abstract":"<p><p>Donor-specific immunomodulatory cells (DSIMC) have successfully induced donor-specific tolerance in clinical living donor liver transplantation. These cells are generated from recipient peripheral blood mononuclear cells (PBMCs) stimulated with irradiated donor PBMC in the presence of costimulatory blockade, yielding a heterogeneous population of recipient-derived immune cells including T cells, B cells, and NK cells, in which CD4<sup>+</sup> regulatory T cells (Tregs) are thought to play a central role. Here, we examined the cell populations and functions crucial for donor-specific immunomodulation within the DSIMC product. DSIMC were generated from PBMC of healthy volunteers using belatacept to achieve costimulatory blockade. Tregs were enriched by CD4<sup>+</sup>CD25<sup>+</sup> magnetic-cell activated cell sorting (MACS) or CD25<sup>+</sup>CD127<sup>-/low</sup> fluorescence-activated cell sorting (FACS). CD4<sup>+</sup>, CD8<sup>+</sup>, CD19<sup>+</sup>, and CD25<sup>+</sup>CD127<sup>-/low</sup> fractions were also individually depleted from DSIMC. Immunomodulatory function of each resulting population was assessed by tritium-labelled thymidine incorporation in mixed lymphocyte cultures (MLC), and cytokine-producing capacity was evaluated by ELISA/ELISpot assays. Unsorted DSIMC exhibited donor-specific suppression at lower cell numbers than CD4<sup>+</sup>CD25<sup>+</sup> enriched cells, while CD4<sup>+</sup>CD25<sup>-</sup> T cells showed no immunosuppressive effect. Depletion of CD4<sup>+</sup>, CD8<sup>+</sup>, or CD19<sup>+</sup> cells did not substantially impair immunomodulatory function. In contrast, depletion of the CD25<sup>+</sup>CD127<sup>-/low</sup> fraction reduced inhibitory function and abolished donor specificity. Depletion of CD4<sup>+</sup> or CD25<sup>+</sup>CD127<sup>-/low</sup> reduced IFN-γ and IL-10 production in response to donor stimulation compared with unsorted DSIMC, implicating CD4<sup>+</sup> Tregs as important contributors to cytokine production under allogeneic stimulation. Furthermore, Treg expansion following donor antigen restimulation was observed in unsorted DSIMC but not in CD4<sup>+</sup>CD25<sup>+</sup>-enriched cells, suggesting that Tregs can be induced from non-Treg CD4<sup>+</sup> populations within the DSIMC. In conclusion, CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>-/low</sup>FoxP3<sup>+</sup>-associated cells appear to contribute to donor-specific immunomodulation; however, the enrichment of CD4<sup>+</sup>CD25<sup>+</sup> T cell diminished DSIMC efficacy. Since the unsorted DSIMC showed stronger activity, we suggest that multiple cell populations may act together to mediate the DSIMC effect.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261473440"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Image cytometry differentiates CD34+ and CD133+ profiles of very small embryonic-like stem cells. 图像细胞术可区分非常小的胚胎样干细胞的CD34+和CD133+谱。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2026-01-01 Epub Date: 2026-02-19 DOI: 10.1177/09636897261422302
David M Smadja, Anna Chipont, Léa Guyonnet, Alexandre G Lellouch, Audrey Cras, Marion Alcantara, Coralie L Guerin
{"title":"Image cytometry differentiates CD34<sup>+</sup> and CD133<sup>+</sup> profiles of very small embryonic-like stem cells.","authors":"David M Smadja, Anna Chipont, Léa Guyonnet, Alexandre G Lellouch, Audrey Cras, Marion Alcantara, Coralie L Guerin","doi":"10.1177/09636897261422302","DOIUrl":"10.1177/09636897261422302","url":null,"abstract":"<p><p>Very small embryonic-like stem cells (VSELs) have been identified as potential precursors of the endothelial lineage in humans. Traditionally characterized by CD34 and CD133 markers, these populations remain poorly delineated, particularly regarding their morphological traits. Leveraging recent advances in imaging flow cytometry (iFC), this study sought to refine the characterization of VSELs by analyzing CD34<sup>+</sup> and CD133<sup>+</sup> Lin<sup>⁻</sup> CD45<sup>⁻</sup> cells from various sources, including bone marrow (BM), mobilized blood (MB), peripheral blood (PB), and cord blood (CB). Using high-resolution iFC, we assessed cell circularity and size, identifying significant morphological differences within subpopulations smaller than 7 µm. CD133<sup>+</sup> cells predominantly exhibited irregular shapes, whereas CD34<sup>+</sup> cells, regardless of CD133 co-expression, were mostly circular. Quantification across multiple sources revealed an enrichment of small circular CD34<sup>+</sup> cells, especially in BM, MB, and CB. A comparative analysis with conventional flow cytometry (cFC) showed similar counts for CD34<sup>+</sup> cells between methods (<i>P</i> = 0.06) but a significantly higher number of CD133<sup>+</sup> cells with cFC (<i>P</i> < 0.0001), reflecting its inability to assess morphology. These findings highlight iFC as a powerful tool for rare stem cell analysis and propose CD34, rather than CD133, as a more reliable marker for identifying circular VSELs under 7 µm, refining future stem cell-isolation strategies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261422302"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Tacrolimus, Sirolimus, Age, and Body Mass Index on the Occurrence of Skin Cancer and Islet Dysfunction After Transplantation. 他克莫司、西罗莫司、年龄和体重指数对移植后皮肤癌和胰岛功能障碍发生的影响。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2025-01-01 DOI: 10.1177/09636897241309412
Christopher Orr, Jeannette Stratton, Mohamed El-Shahawy, Elena Forouhar, Alice Peng, Gagandeep Singh, Keiko Omori, Meirigeng Qi, Fouad Kandeel
{"title":"Impact of Tacrolimus, Sirolimus, Age, and Body Mass Index on the Occurrence of Skin Cancer and Islet Dysfunction After Transplantation.","authors":"Christopher Orr, Jeannette Stratton, Mohamed El-Shahawy, Elena Forouhar, Alice Peng, Gagandeep Singh, Keiko Omori, Meirigeng Qi, Fouad Kandeel","doi":"10.1177/09636897241309412","DOIUrl":"10.1177/09636897241309412","url":null,"abstract":"<p><p>Herein, we characterized the percentage of tacrolimus to the combined sirolimus and tacrolimus trough levels (tacrolimus %) observed during islet transplant-associated immune suppression therapy with post-transplant skin cancer. Although trough levels of tacrolimus and sirolimus were not different (<i>P</i> = 0.79, 0.73, respectively), high tacrolimus % resulted in a 1.32-fold increase in skin cancer odds when adjusting for age, sex, body mass index (BMI), and use of mycopheonlate mofetil (MMF; <i>p</i> = 0.039). Skin cancer patients were likely to have been older but not differ significantly (mean difference 12 years, <i>P</i> = 0.056), but age was significantly associated with a 1.22-fold increase in adjusted skin cancer odds (<i>P</i> = 0.046). BMI was inversely associated with skin cancer, with an adjusted odds ratio (OR) of 0.40 (<i>P</i> = 0.022). High tacrolimus % (>35) resulted in a 4.6-fold increase in skin cancer frequency, whereas sirolimus above 75% of the combined therapy led to a 5.2-fold increase in islet graft dysfunction (IGD) events/year. By calculating the maximum safe exposure (MSE) to tacrolimus % according to patient age and BMI, we found that cumulative months spent above MSE was predictive of skin cancer (1.20-fold increase, <i>P</i> = 0.003). Individuals exceeding the MSE for 1 year were 9.2 times more likely to develop skin cancer (<i>P</i> = 0.008). Results suggest that strategies targeting immunosuppression ratios based on age and BMI may minimize cancer risk while improving graft survival and function.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241309412"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Shorter Digestion Times of Donor Islets Is Associated With Better Islet Graft Function After Islet Transplantation. 胰岛移植后供体胰岛消化时间越短,胰岛移植功能越好。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2025-01-01 DOI: 10.1177/09636897241310989
Chia-Hao Wang, Christopher Orr, Jeannette Hacker-Stratton, Mohamed El-Shahawy, Keiko Omori, Meirigeng Qi, Fouad Kandeel
{"title":"Shorter Digestion Times of Donor Islets Is Associated With Better Islet Graft Function After Islet Transplantation.","authors":"Chia-Hao Wang, Christopher Orr, Jeannette Hacker-Stratton, Mohamed El-Shahawy, Keiko Omori, Meirigeng Qi, Fouad Kandeel","doi":"10.1177/09636897241310989","DOIUrl":"10.1177/09636897241310989","url":null,"abstract":"<p><p>Although islet transplantation is effective in reducing severe hypoglycemia events and controlling blood glucose in patients with type 1 diabetes, maintaining islet graft function long-term is a significant challenge. Islets from multiple donors are often needed to achieve insulin independence, and even then, islet function can decline over time when metabolic demand exceeds islet mass/insulin secretory capacity. We previously developed a method that calculated the islet graft function index (GFI) and a patient's predicted insulin requirement (PIR) using mathematical nonlinear regression. Both PIR and GFI could be used by physicians as tools to monitor islet graft function and to guide supplementing the patient with exogenous insulin to prevent beta-cell exhaustion. This study investigates the factors relating to the islet preparation process, as well as donor and recipient characteristics, and assessed their associations with PIR and GFI after transplantation. The goal is to determine the most relevant factors that influence islet graft function after transplantation. We examined the effects of donor and recipient characteristics, and islet processing factors on posttransplanted PIR and GFI. The PIR and GFI at 3 months were calculated using patients' baseline insulin intake, posttransplant 2-h postprandial blood glucose, and glucagon-stimulated C-peptide. Thirteen transplants that resulted in progressive decline in patients' weekly averaged insulin intake over the initial weeks after transplant (assuming constant glucose level) with available 3-month PIR and GFI data were chosen for the investigation. Univariate analyses were performed to assess the effects of donor and recipient characteristics and islet processing factors on islet graft function as reflected by PIR and GFI. The PIR and GFI were treated as continuous response variables in separate linear regression models. Shorter digestion time of isolated donor islets were associated with lower PIR (<i>P</i> = 0.014) and a higher GFI (<i>P</i> = 0.027) after transplantation. Islet injury related to digestion enzyme exposure influenced islet function as estimated using PIR and GFI post-transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241310989"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Standardized dynamic glucose testing reveals donor-dependent heterogeneity in human islet function. 标准化动态葡萄糖测试揭示了人类胰岛功能的供体依赖性异质性。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2025-01-01 Epub Date: 2025-10-14 DOI: 10.1177/09636897251350654
Priyadarshini Gnanasekar, Chiara Saponaro, Markus Mühlemann, Chimene Amayene Amassogo, Anais Coddeville, Julien Thevenet, Nathalie Delalleau, Pauline Petit, Arnaud Hanssen, Gianni Pasquetti, Valentin Lericque, Mikael Chetboun, Violeta Raverdy, Isabel Gonzalez-Mariscal, Marie-Christine Vantyghem, Caroline Bonner, François Pattou, Julie Kerr-Conte, Valery Gmyr
{"title":"Standardized dynamic glucose testing reveals donor-dependent heterogeneity in human islet function.","authors":"Priyadarshini Gnanasekar, Chiara Saponaro, Markus Mühlemann, Chimene Amayene Amassogo, Anais Coddeville, Julien Thevenet, Nathalie Delalleau, Pauline Petit, Arnaud Hanssen, Gianni Pasquetti, Valentin Lericque, Mikael Chetboun, Violeta Raverdy, Isabel Gonzalez-Mariscal, Marie-Christine Vantyghem, Caroline Bonner, François Pattou, Julie Kerr-Conte, Valery Gmyr","doi":"10.1177/09636897251350654","DOIUrl":"10.1177/09636897251350654","url":null,"abstract":"<p><p>Glucose-stimulated insulin secretion (GSIS) testing of isolated islets of Langerhans is crucial for assessing β-cell function, yet protocol variability complicates result interpretation. This study investigated insulin secretion heterogeneity across 576 donors and examined the influence of donor characteristics on secretory responses. We compared static incubation (<i>n =</i> 408) and dynamic perifusion (<i>n =</i> 168) techniques using standardized glucose stimulation protocols (3 vs 15 mM). While both methods showed comparable stimulation indices (<i>r</i><sup>2</sup> = 0.652), dynamic perifusion uniquely captured temporal secretion patterns and revealed greater dynamic range in insulin responses. Notably, dynamic perifusion, with insulin content normalization, revealed a 22-fold variation in stimulation index across donors. Body mass index (BMI) and HbA1c significantly influenced basal insulin secretion, particularly in donors with glucose intolerance and type 2 diabetes (T2D) (HbA1c ≥ 6.5%). Cluster analysis identified two distinct groups based on age, BMI/body surface area (BSA), and HbA1c, which strongly predicted insulin secretion patterns, whereas donor sex had no measurable impact. This large-scale study demonstrates the superiority of standardized perifusion over static incubation for resolving islet glucose responses. By capturing dynamic secretion profiles, perifusion reveals substantial donor heterogeneity, primarily driven by BMI and HbA1c through their effects on basal insulin secretion.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251350654"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145539408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The impact of tacrolimus levels on acute GVHD and transplant outcomes in haploidentical hematopoietic stem cell transplantation: A retrospective analysis. 他克莫司水平对单倍同型造血干细胞移植急性GVHD和移植结果的影响:回顾性分析。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2025-01-01 Epub Date: 2025-08-14 DOI: 10.1177/09636897251366368
Alexander Nikoloudis, Veronika Buxhofer-Ausch, Ameya Kunte, Christina Groiss, Lorenz Mair, Christoph Aichinger, Michaela Binder, Petra Hasengruber, Emine Kaynak, Dagmar Wipplinger, Robert Milanov, Irene Strassl, Olga Stiefel, Sigrid Machherndl-Spandl, Holger Rumpold, Ansgar Weltermann, Andreas Petzer, Johannes Clausen
{"title":"The impact of tacrolimus levels on acute GVHD and transplant outcomes in haploidentical hematopoietic stem cell transplantation: A retrospective analysis.","authors":"Alexander Nikoloudis, Veronika Buxhofer-Ausch, Ameya Kunte, Christina Groiss, Lorenz Mair, Christoph Aichinger, Michaela Binder, Petra Hasengruber, Emine Kaynak, Dagmar Wipplinger, Robert Milanov, Irene Strassl, Olga Stiefel, Sigrid Machherndl-Spandl, Holger Rumpold, Ansgar Weltermann, Andreas Petzer, Johannes Clausen","doi":"10.1177/09636897251366368","DOIUrl":"10.1177/09636897251366368","url":null,"abstract":"<p><p>The impact of early tacrolimus (TAC) blood levels on acute graft-versus-host disease (aGVHD) and transplant outcomes in adults undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with posttransplant cyclophosphamide (PTCy) is incompletely investigated. We retrospectively analyzed 161 T-cell-replete haplo-HSCT with PTCy, TAC, and mycophenolate-mofetil. TAC trough levels from weeks 1-2 (w1/2) and weeks 3-4 (w3/4) posttransplant were categorized as \"Low\" or \"High\" using a threshold of 10 ng/ml. Outcomes assessed included grade III-IV acute graft-versus-host-disease (aGVHD), nonrelapse mortality (NRM), relapse, and overall survival (OS). Multivariate analyses controlled for relevant patient and transplant factors. Higher w1/2 TAC (≥10 ng/ml) in weeks 1-2 had no association with aGVHD III/IV (35% vs. 35%, <i>P</i> = 0.71). Higher TAC levels during w3/4 were associated with a trend toward decreased aGVHD III-IV incidence (8% vs. 20%; <i>P</i> = 0.09). Multivariate analysis confirmed w3/4 TAC levels as protective against aGVHD III/IV (sub-Hazard Ratio [sHR] = 0.83, 95% CI: 0.70-0.98, <i>P</i> = 0.03) and NRM (sHR = 0.82, 95% CI: 0.71-0.95, <i>P</i> = 0.01), while w1/2 TAC levels had no significant impact on the above outcomes. TAC levels did not significantly impact OS or relapse. We conclude that following PTCy-based haplo-HSCT, higher TAC levels during weeks 3-4 may decrease aGVHD and NRM.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251366368"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Applicability of regenerative oligodendrocyte precursor cell optic nerve transplantation in rat model of demyelinating disease. 再生少突胶质前体细胞视神经移植在脱髓鞘病大鼠模型中的适用性。
IF 3.7 4区 医学
Cell Transplantation Pub Date : 2025-01-01 Epub Date: 2025-10-15 DOI: 10.1177/09636897251378231
Itay Lotan, Benjamin R Johnston, Shuhei Nishiyama, Jin Myoung Seok, Amy Wright, Stanley Bazarek, Michael Levy
{"title":"Applicability of regenerative oligodendrocyte precursor cell optic nerve transplantation in rat model of demyelinating disease.","authors":"Itay Lotan, Benjamin R Johnston, Shuhei Nishiyama, Jin Myoung Seok, Amy Wright, Stanley Bazarek, Michael Levy","doi":"10.1177/09636897251378231","DOIUrl":"10.1177/09636897251378231","url":null,"abstract":"<p><p>Cell-based therapies, particularly transplanted human oligodendrocyte progenitor cells (OPCs), are being explored for neuroprotection and remyelination in demyelinating diseases of the central nervous system (CNS). In this study, we investigated the potential of OPC transplantation into the optic nerve of dark agouti (DA) rats with experimental autoimmune encephalomyelitis (EAE). Human OPCs were transplanted 30 days after EAE induction in one optic nerve, while the contralateral nerve was injected with a vehicle. FTY720 (fingolimod) was administered starting from day 25 post-EAE to prevent graft rejection. Rats were monitored clinically and electrophysiologically using visually evoked potentials (VEPs) for up to 90 days post-transplant. Histological analysis of OPC viability, myelin, and axonal integrity was performed on days 30, 60, and 90 post-transplant. At days 30 and 60, sparse OPCs were detected in the injected optic nerve. However, no live cells were detected on day 90. There were no significant differences in myelin or axonal integrity between the OPC- and vehicle-injected nerves. The VEP traces were severely distorted throughout the 90-day follow-up. This approach did not show long-term viability following direct injection of OPCs in the optic nerve of EAE rats. Challenges related to graft rejection and cell transplantation are discussed, with implications for future research in cell-based therapies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251378231"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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