Current perspectives on mesenchymal stromal cell therapy for graft versus host disease

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(6), P. 613 - 625

Published: May 10, 2023

Abstract Graft versus host disease (GvHD) is the clinical condition in which bone marrow-derived mesenchymal stromal cells (MSCs) have been most frequently studied. In this review, we summarize experience from trials that paved way to translation. While MSC-based therapy has shown an exceptional safety profile, identifying potency assays and biomarkers reliably predict capacity of a specific MSC batch alleviate GvHD difficult. As diagnosis staging are based solely on criteria, individual patients recruited same trial may vastly different underlying biology, obscuring outcomes making it difficult determine benefit MSCs subgroups patients. An accumulating body evidence indicates importance considering not only cell product but also patient-specific and/or immune characteristics determining responsiveness. A mode action where intravascular destruction followed by monocyte-efferocytosis-mediated skewing repertoire permissive inflammatory environment would both explain why engraftment irrelevant for efficacy stress biologic differences between responding nonresponding We recommend combined analysis activity identify with who likely therapy.

Language: Английский

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The Applications of Machine Learning in the Management of Patients Undergoing Stem Cell Transplantation: Are We Ready?

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 395 - 395

Published: Jan. 25, 2025

Hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for hematologic malignancies, such as leukemia and lymphoma other severe conditions but associated with significant risks, including graft versus host disease (GVHD), relapse, treatment-related mortality. The increasing complexity of clinical, genomic, biomarker data has spurred interest in machine learning (ML), which emerged transformative tool to enhance decision-making optimize outcomes HSCT. This review examines the applications ML HSCT, focusing on donor selection, conditioning regimen, prediction post-transplant outcomes. Machine approaches, decision trees, random forests, neural networks, have demonstrated potential improving compatibility algorithms, mortality relapse prediction, GVHD risk stratification. Integrating “omics” models enabled identification novel biomarkers development highly accurate predictive tools, supporting personalized treatment strategies. Despite promising advancements, challenges persist, standardization, algorithm interpretability, ethical considerations regarding patient privacy. While holds promise revolutionizing HSCT management, addressing these barriers through multicenter collaborations regulatory frameworks remains essential broader clinical adoption. In addition, can cope some harmonization, patients’ protection, availability adequate infrastructure. Future research should prioritize larger datasets, multimodal integration, robust validation methods fully realize ML’s

Language: Английский

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Chronic graft-versus-host disease: Unresolved complication or ancient history?

Blood, Journal Year: 2024, Volume and Issue: 144(13), P. 1363 - 1373

Published: July 15, 2024

Language: Английский

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Chronic Graft-versus-host Disease, Part 2: Clinical Success and Roadmap to the Future

Transplantation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Chronic graft-versus-host disease (cGVHD) is an immune-mediated, heterogeneous, multiorgan complication affecting allogeneic hematopoietic cell transplantation recipients, leading to increased morbidity, mortality, and decline in health-related quality-of-life. Advances understanding the complex pathophysiology, collaborative efforts lead by National Institutes of Health standardize criteria for clinical trials, led bench-to-bedside resulting development 4 US Food Drug Administration-approved agents treatment steroids-refractory cGVHD since 2017. Despite remarkable advances field prevention cGVHD, more options, outcome patients with moderate-severe remains suboptimal. Essential successful management recognize at early stages before onset irreversible damage, allowing personalized multidisciplinary specialized interventions that include pharmacologic therapies additional supportive care measures. The aim this review summarize key areas active research new developments therapeutic approaches, focus on (1) preemptive therapy, (2) upfront therapy beyond corticosteroids, (3) refractory novel agents, role combination therapies, organ-specific (4) challenges, gaps, future directions.

Language: Английский

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Dynamic forecasting module for chronic graft-versus-host disease progression based on a disease-associated subpopulation of B cells: a multicenter prospective study

EBioMedicine, Journal Year: 2025, Volume and Issue: 113, P. 105587 - 105587

Published: Feb. 12, 2025

Language: Английский

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Inflammation and Immune Reactions in the Fetus as a Response to COVID-19 in the Mother

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(13), P. 4256 - 4256

Published: June 25, 2023

Background: Contracting COVID-19 during pregnancy can harm both the mother and unborn child. Pregnant women are highly likely to develop respiratory viral infection complications with critical conditions caused by physiological changes in immune cardiopulmonary systems. Asymptomatic pregnant may be accompanied fetal inflammatory response syndrome, which has adverse consequences for newborn’s life health. Purpose: To conduct an assessment of fetus due effects on determining pro-inflammatory cytokines, cell markers, T regulatory cells, response, evaluation cardiac function, thymus size. Materials methods: A prospective study included (n = 92). The main group consisted 62 infection: subgroup 1—SARS-CoV-2 PCR-positive 4–6 weeks before delivery 30); 2—SARS-CoV-2 earlier 32). control 30 healthy women. In all women, levels circulating cytokines chemokines (IL-1α, IL-6, IL-8, IL-10, GM-CSF, TNF-α, IFN-γ, MIP-1β, CXCL-10) were determined peripheral blood after umbilical cord blood, analysis was performed markers dendritic quantitative functional characteristics specific responses. thyroxine thyroid-stimulating hormone newborns studied groups, ultrasound examinations echocardiography heart also performed. Results: cells born mothers who suffered from (subgroup 1) showed a significant increase CD80 CD86 expression compared (p 0.023). samples children whose tested positive 1), CD4+CCR7+ increased concomitant decrease proportion naive CD4+ 0.016). Significantly higher detected 1 group. 1, activity suppressed, < 0.001). severe coronavirus infection, weak them as well their newborns. size, transient hypothyroxinemia, parameters according revealed Conclusions: Fetal syndrome occur infants is characterized activation system production cytokines. disease severity woman does not correlate SIRS neonatal period. It vary minimal laboratory parameter development organs systems newborn.

Language: Английский

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Cognitive impairments correlate with increased central nervous system immune activation after allogeneic haematopoietic stem cell transplantation

Leukemia, Journal Year: 2023, Volume and Issue: 37(4), P. 888 - 900

Published: Feb. 15, 2023

Abstract Murine studies indicate that, after allogeneic haematopoietic stem cell transplantation (aHSCT), donor-derived macrophages replace damaged microglia and alloreactive T-cells invade the central nervous system (CNS). The clinical relevance of this is unknown. We assessed CNS immune surveillance metabolic activity involved in neuronal survival, relation to fatigue cognitive dysfunction 25 long-term survivors aHSCT. Patients with exhibited increased proportions activated CD16 + NK-cells cerebrospinal fluid (CSF). Immune activation was paralleled reduced levels anti-inflammatory factors T-cell suppression (transforming growth factor-β, programmed death ligand-1), NK-cell regulation (poliovirus receptor, nectin-2), macrophage (CD200, chemokine [C-X3-C motif] ligand-1). Additionally, CSF mRNA expression pattern associated neuroinflammation oxidative stress. Furthermore, proteomic, transcriptomic demonstrated decreased neuroprotective factors, an upregulation apoptosis pathway genes. kynurenine tryptophan metabolism all aHSCT patients, resulting accumulation neurotoxic pro-inflammatory metabolites. Cognitive decline are overlooked but frequent complications This study links post-transplant inflammation neurotoxicity our previously reported hypoactivation prefrontal cortex during testing, suggesting novel treatment targets.

Language: Английский

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Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD

Bone Marrow Transplantation, Journal Year: 2024, Volume and Issue: 59(5), P. 680 - 687

Published: Feb. 21, 2024

Language: Английский

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Recent advances and research progress in biomarkers for chronic graft versus host disease

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 186, P. 103993 - 103993

Published: April 13, 2023

Language: Английский

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Intrauterine activation of the fetal immune system in response to maternal COVID-19

Obstetrics Gynecology and Reproduction, Journal Year: 2023, Volume and Issue: 17(2), P. 188 - 201

Published: May 19, 2023

Introduction . During pregnancy COVID-19 poses a serious threat to both maternal health and of paired unborn child. Pregnant women have high probability complications due respiratory viral infections followed by developing critical conditions caused physiologically altered immune cardiopulmonary systems. However, asymptomatic in pregnant may be accompanied fetal inflammatory response syndrome (FIRS) that results unfavorable sequelae for neonatal life health. Aim : assess resulting from pregnancy. Materials М ethods A prospective randomized comparative study involving 92 was carried out. The main group included 62 convalescent women: subgroup 1 consisted 30 found positive SARS-CoV-2 using polymerase chain reaction (PCR) 4–6 weeks before delivery; 2 – 32 with detected PCR earlier during control enrolled healthy women. level circulating cytokines interleukins (IL) IL-1α, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis alpha (TNF-α), interferon gamma (IFN-γ), macrophage protein-1β (MIP-1β), C-X-C motif chemokine ligand 10 (CXCL-10) cell markers (CD86, CD80, CD4, CD25, CCR7) were analyzed. In addition, all neonates underwent thymus gland ultrasound screening. Results. Cord blood dendritic cells born mothers vs. showed significantly upregulated expression CD80 CD86 (p = 0.023). Moreover, such cord samples increased percentage CD4+, CCR7+ T paralleled decreased proportion naive CD4+ as compared 0.016). It count regulatory CD4+CD25+Foxp3+ (Treg) did not differ significantly, whereas Treg functional activity severe (subgroup 2) suppressed. Significantly higher proinflammatory chemokines < 0.05). the peripheral groups upon delivery changed insignificantly. SARS-CoV-2-positive strong antigen-specific response. reduced size mothers. Conclusion Fetal occurs COVID-19, which is characterized activated system production pro-inflammatory cytokines. disease severity has no correlation FIRS intensity period can vary minimally laboratory parameters at organ body levels.

Language: Английский

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