{"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":3.2,"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}
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":3.2,"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}
{"title":"Efficacy and safety of Bio 3D conduits composed of human umbilical cord-derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model.","authors":"Kazuaki Fujita, Ryosuke Ikeguchi, Tomoki Aoyama, Takashi Noguchi, Koichi Yoshimoto, Daichi Sakamoto, Terunobu Iwai, Tetsuya Miyamoto, Yudai Miyazaki, Shizuka Akieda, Tokiko Nagamura-Inoue, Fumitaka Nagamura, Koichi Nakayama, Shuichi Matsuda","doi":"10.1177/09636897251361711","DOIUrl":"10.1177/09636897251361711","url":null,"abstract":"<p><p>Peripheral nerve injuries involving nerve defects remain challenging to treat. Although autologous nerve grafting is considered the gold standard, it has notable limitations, including donor site morbidity. To address this, we developed a scaffold-free Bio 3D conduit composed of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) using bioprinting technology. In this study, we evaluated its efficacy and safety in a canine ulnar nerve defect model. At 10 weeks postoperatively, the Bio 3D group showed better motor and sensory recovery compared with the allograft group, as demonstrated by the pinprick test, electrophysiological studies, and hypothenar muscle wet weight (0.978 ± 0.100 vs. 0.637 ± 0.151, n = 3). Morphometric analysis revealed greater axonal regeneration, including larger myelinated axon diameters (4.27 ± 0.342 µm vs. 3.69 ± 0.161 µm, n = 3) and thicker myelin sheaths (0.621 ± 0.088 µm vs. 0.497 ± 0.021 µm, n = 3). Immunostaining showed that the number of transplanted UC-MSCs diminished over time, likely after exerting their therapeutic effects. No adverse events, systemic abnormalities, or distant human cell migration was observed. These findings suggest that UC-MSC-derived Bio 3D conduits are a promising alternative for peripheral nerve regeneration, especially for patients wishing to avoid donor nerve harvesting.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251361711"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774744","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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-08-14DOI: 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":3.2,"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}
{"title":"Stem Cell-Based Therapies via Different Administration Route for Stroke: A Meta-analysis of Comparative Studies.","authors":"Gabriella Jeanne Mulia, Novelia Anna, John Chung-Che Wu, Hon-Ping Ma, Yung-Hsiao Chiang, Ju-Chi Ou, Kai-Yun Chen","doi":"10.1177/09636897251315121","DOIUrl":"10.1177/09636897251315121","url":null,"abstract":"<p><p>Stroke, a neurological condition from compromised cerebral blood perfusion, remains a major global cause of mortality and disability. Conventional therapies like tissue plasminogen activator are limited by narrow therapeutic windows and potential adverse effects, highlighting the urgency for novel treatments. Stem cell-based therapies, with their neuroprotective and regenerative properties, present a promising yet highly diverse alternative. By conducting literature search and data extraction from the PubMed, Embase, and Cochrane databases, this meta-analysis assessed the clinical efficacy and safety of stem cell-based therapies administered via intravenous (IV) and non-IV routes in 17 studies with stroke patients. Primary outcomes included the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS), while secondary outcomes included mortality and adverse events. Results demonstrated significant improvements in NIHSS, BI, and mRS scores, particularly in non-IV groups within 6- and 12-month follow-ups, suggesting delayed but enhanced therapeutic efficacy. Mortality was reduced in both IV and non-IV groups, indicating treatment safety. Adverse events, categorized into neurological and systemic complications, showed no significant differences between intervention and control groups, further emphasizing the safety of stem cell therapies. Non-IV routes showed more long-term benefits, potentially due to enhanced cell delivery and integration. These findings demonstrate the potential of stem cell therapies to improve functional recovery and survival in stroke patients, regardless of administration route. However, the delayed response underscores the need for extended follow-up in clinical applications. Further research is required to standardize treatment protocols, optimize cell types and doses, and address patient-specific factors to integrate stem cell therapies into routine clinical practice.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251315121"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381712","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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-03-21DOI: 10.1177/09636897251323339
Li Xing, Ronscardy Mondesir, Logan M Glasstetter, Xiang-Yang Zhu, Bo Lu, Mina Al Saeedi, Gurparneet Kaur Sohi, Alfonso Eirin, Lilach O Lerman
{"title":"The Impact of Obesity on Autophagy in Human Adipose-Derived Mesenchymal Stromal Cells.","authors":"Li Xing, Ronscardy Mondesir, Logan M Glasstetter, Xiang-Yang Zhu, Bo Lu, Mina Al Saeedi, Gurparneet Kaur Sohi, Alfonso Eirin, Lilach O Lerman","doi":"10.1177/09636897251323339","DOIUrl":"10.1177/09636897251323339","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) possess therapeutic properties, which can be blunted by obesity. Autophagy, a cellular recycling process, is essential for MSC function. We investigated the mechanisms by which obesity affects the properties of MSCs, with a focus on autophagy. Adipose tissue was obtained from kidney donors [body mass index (BMI) <30 kg/m<sup>2</sup>, non-obese] or individuals undergoing weight loss surgery (BMI ≥30 kg/m<sup>2</sup>, obese) for MSC harvesting (<i>n</i> = 11 each); samples were randomized to sequencing (seq; <i>n</i> = 5 each) or functional studies (<i>n</i> = 6 each). MSCs were sequenced to determine their epigenetic (5-hydroxymethylcytosine) and transcriptomic profiles across autophagy-related genes using hydroxymethylated DNA immunoprecipitation sequencing and mRNA-seq, respectively. Genes with shared trends in both datasets underwent Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) validation. During functional studies, 2-h starvation was used to induce autophagy <i>in vitro</i>, enabling detection of changes in the protein expression of microtubule-associated protein 1A/1B-light chain-3 and in autophagic flux. Obesity amplified a starvation-induced reduction in autophagic flux in MSCs while promoting earlier generation of new autophagosomes during autophagy initiation. Integrated analysis of the two sequencing datasets revealed 124 differentially hydroxymethylated genes and 30 differentially expressed mRNAs. Among six overlapping autophagy-related genes, three exhibited same-direction trends. Of these, STX12 and SLC25A4 may be implicated in the impact of obesity on autophagic changes in MSCs. Therefore, human obesity may alter autophagy in adipose tissue-derived MSC, and thereby their metabolism and function.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251323339"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673284","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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-04-03DOI: 10.1177/09636897251325673
Wenhan Yang, Zhiyu Pan, Jiacheng Zhang, Lian Wang, Ju Lai, Kai Fan, Jingjing Zhu, Qian Liu, Yalei Dai, Jieyu Zhou, Shuhui Wu, Zhengliang Gao, Shaoqing Yu
{"title":"Administration Strategy-Dependent Mechanisms and Effects of Human Adipose Tissue Stem Cell Extracellular Vesicles in Mouse Allergic Rhinitis Treatment.","authors":"Wenhan Yang, Zhiyu Pan, Jiacheng Zhang, Lian Wang, Ju Lai, Kai Fan, Jingjing Zhu, Qian Liu, Yalei Dai, Jieyu Zhou, Shuhui Wu, Zhengliang Gao, Shaoqing Yu","doi":"10.1177/09636897251325673","DOIUrl":"10.1177/09636897251325673","url":null,"abstract":"<p><p>We previously found that intravenous injection of extracellular vesicles (EVs) from human adipose tissue-derived stem cells (hADSC) could ameliorate allergic rhinitis (AR) in mice through immunomodulatory effects. In clinical trials, nasal delivery has been an attractive treatment for AR. We sought to determine whether there are differences in the therapeutic effects between caudal injection and their combination. We treated AR mice with ADSC-EVs via caudal vein, nasal cavity, or both. After treatment, the mice were re-sensitized and the indices of behavior, nasal mucosa morphology, and cytokine secretion of the mice under different modes of administration were calculated. The resultes show that tail vein, nasal, and combined administration could effectively relieve the inflammatory infiltration of the nasal mucosa of mice, reduce the secretion of IgE, IL-4, and other inflammatory factors, and alleviate the Th1/Th2 imbalance. Injection and nasal delivery, as well as their combination, effectively alleviated the symptoms of rhinitis in mice. Nasal administration has a better therapeutic effect when the inflammatory response is mild. It could be speculated that ADSC-EVs have excellent properties in the treatment of AR, and modes of administration can be selected for different stages of treatment in clinical therapy.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251325673"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779088","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}
{"title":"Therapeutic and continuative effects of human umbilical cord-derived mesenchymal stromal cells in food-allergic mice.","authors":"Yuan Zhao, Yabing Ding, Zhaoyan Wang, Qian Wang, Dou Ye, Zuo Luan","doi":"10.1177/09636897251326899","DOIUrl":"10.1177/09636897251326899","url":null,"abstract":"<p><p>This study aimed to investigate the impact of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) on food allergy (FA) mice induced by ovalbumin. The percentage of regulatory T cells (Tregs) was assessed by administering hUC-MSCs intravenously to FA mouse models with oral challenges, allergic responses and levels of related allergic cytokines. The phenotypes of hUC-MSCs were analysed using flow cytometric analysis. Immunohistochemistry was used for histology observation. Real-time polymerase chain reaction (PCR) was used for gene expression. Jejunum tissue was analysed by transcriptome sequencing. Our results demonstrated that in the current FA model, hUC-MSC therapy significantly alleviated allergic responses and diarrhoea. Levels of immunoglobulin E (IgE), as well as cytokines, such as interleukin (IL)-6 and tumour necrosis factor-α associated with T helper 2 cells, were reduced. Conversely, transforming growth factor (TGF)-β levels increased with hUC-MSC therapy. In addition, enhanced TGF-β expression along with IL-10 messenger ribonucleic acid levels and an increased percentage of CD4<sup>+</sup>Foxp3<sup>+</sup> Tregs were observed. In long-term FA mice models, hUC-MSC therapy exhibited sustained effects in mitigating rectal temperature decrease and mortality rates while reducing the levels of IgE, IL-6 and proportion of IgE+ cells; it also elevated TGF-β levels. Furthermore, hUC-MSC therapy attenuated pathological injury in both current and long-term FA mouse models. Transcriptome sequencing showed that upregulated differentially expressed genes were mainly concentrated in neural activation-ligand interaction, the cyclic guanosine monophosphate-protein kinase G signalling pathway and the TGF-β signalling pathway. The hUC-MSC therapy holds promise for alleviating both immediate and persistent FA conditions; targeting TGF-β and IL-10 secreted by hUC-MSCs may be a potential approach for treating FA.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251326899"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718085","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}
{"title":"Role of Leucine-Rich Repeat-Containing G-Protein-Coupled Receptors 4-6 (LGR4-6) in the Ovary and Other Female Reproductive Organs: A Literature Review.","authors":"Yu-Hsun Chang, Kun-Chi Wu, Kai-Hung Wang, Dah-Ching Ding","doi":"10.1177/09636897241303441","DOIUrl":"10.1177/09636897241303441","url":null,"abstract":"<p><p>Leucine-rich repeat-containing G-protein-coupled receptors regulate stem cell activity and tissue homeostasis within female reproductive organs, primarily through their interaction with the Wnt/β-catenin signaling pathway. LGR4-6 are increasingly recognized for their roles in organ development, regeneration, and cancer. This review aims to provide a comprehensive overview of the roles of LGR4-6 in female reproductive organs, highlighting their significance in normal physiology and disease states, specifically in the context of ovarian cancer. LGR4 is essential for the proper development of the female reproductive system; its deficiency leads to significant reproductive abnormalities, including delayed menarche and follicle development issues. LGR5 is a well-established marker of stem cells in the ovary and fallopian tubes. It has been implicated in the pathogenesis of high-grade serous ovarian cancer. LGR6, while less studied, shares functional similarities with LGR5 and can maintain stemness. It contributes to chemoresistance in ovarian cancer. LGR6 is a marker for fallopian tube stem cells and is involved in stem cell maintenance and differentiation. LGR4-6 regulate the pathophysiology of female reproductive tissues. LGR4-6 are promising therapeutic targets for treating reproductive cancers and other related disorders. Molecular mechanisms underlying the functions of LGR4-6 should be studied.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241303441"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057898","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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-08-08DOI: 10.1177/09636897251362031
Jian Wang, Yaning Shi, Yuehan Su, Chaoyue Pang, Yimiao Yang, Weiwei Wang
{"title":"Research advances of extracellular vesicles in lung diseases.","authors":"Jian Wang, Yaning Shi, Yuehan Su, Chaoyue Pang, Yimiao Yang, Weiwei Wang","doi":"10.1177/09636897251362031","DOIUrl":"10.1177/09636897251362031","url":null,"abstract":"<p><p>The lung is a vital organ in the respiratory system, and there is a critical need to develop more effective methods for lung health management. Extracellular vesicles (EVs) play an important role in intercellular communication. They exhibit high bioavailability and low immunogenicity, making them essential in maintaining cellular homeostasis and in the prevention and treatment of numerous diseases. This review describes the diverse sources, isolation techniques, functions, and challenges associated with EVs, particularly exosomes. We highlight their significant role in the diagnosis and treatment of lung diseases, as well as their potential as drug delivery vehicles. By synthesizing recent advances in EVs research, this review aims to provide a theoretical foundation for future studies and clinical applications of EVs.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251362031"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798299","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}