In vivo Monitoring of Neutrophil Function in Patients after Stem Cell Transplant
干细胞移植后患者中性粒细胞功能的体内监测
基本信息
- 批准号:10679553
- 负责人:
- 金额:$ 81.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-02-13 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAntifungal AgentsAzolesBiological MarkersCSF3 geneCandidaCandida albicansCandida aurisCandidiasisCellsCommunicationDiagnosisEarly DiagnosisEffectivenessEngineeringEnrollmentFunctional disorderFungal Drug ResistanceFutureGoalsGrowthHematologic NeoplasmsHematopoietic Stem Cell TransplantationHospitalizationHumanHyphaeImageImaging TechniquesImmune responseIn VitroIndividualInfectionInjuryKnowledgeLabelLeukocytesLifeMalignant NeoplasmsMeasurementMeasuresMicroscopicMolecularMonitorMorbidity - disease rateMycosesOutcomePatientsPerformancePhagocytosisPopulationPredispositionProceduresProphylactic treatmentRecoveryResearchResistanceRiskRisk EstimateRisk FactorsRisk ReductionRoleSiteStem cell transplantTechniquesTherapeuticTimeTransplant RecipientsTransplantationaccurate diagnosiscandidemiachemokinecytokinedesignfirst responderfunctional restorationfungushigh riskhuman imagingimprovedimproved outcomein vivoin vivo monitoringinfection riskleukemiamortalityneutrophilnovel imaging technologypatient stratificationpost-transplantrestorationtissue injurytool
项目摘要
Hematopoietic stem cell transplant (HSCT), an essential procedure in the treatment of patients with
hematological malignancies, also temporarily increases the risk for infections with invasive fungi. The recovery
in the neutrophil number after HSCT is commonly regarded as a key metric for the restoration of antifungal
defenses. However, the metric is imprecise, and there is an urgent need for new biomarkers to help identify the
patients at risk. In the absence of new tools, the management of invasive fungal infections remains remarkably
challenging. The long-term goal of this research is to engineer new tools and validate new metrics estimating
the risk for invasive fungal infections in HSCT patients. Achieving this goal requires a focus on neutrophil
swarming function, which is critical in effective antifungal immune responses. Swarming is distinct from
phagocytosis in that it involves neutrophil-neutrophil communication that helps coordinate the activities of
multiple cells toward blocking the growth of invasive fungi. The focus on neutrophil swarming is justified by
preliminary results showing that in HSCT patients, even when the neutrophil count recovered at 4 weeks after
transplant, a neutrophil swarming deficiency is still present and is substantial. Knowledge about how neutrophil
swarming deficiency is resolved over time after HSCT is currently lacking. To address this knowledge gap and
evaluate the utility of new biomarkers we will pursue the following specific aims: 1) Determine neutrophil
swarming parameters that are distinct in healthy and HSCT patients. 2) Determine what cytokines help restore
the swarming activity of neutrophils from HSCT patients and 3) Design new imaging techniques for label-free
tracking of human neutrophils responding to microscopic tissue injuries in vivo. If successful, the proposed
research could have a major impact on the lives of HSCT patients by improving the monitoring of their recovery
and by identifying potential strategies for accelerating the recovery of their neutrophil functions and improving
their protection against fungal infections.
造血干细胞移植(HSCT)是治疗慢性髓细胞白血病患者的一项基本程序
血液系统恶性肿瘤也会暂时增加感染侵袭性真菌的风险。经济复苏
在HSCT后中性粒细胞数量通常被认为是抗真菌恢复的关键指标
防御。然而,该指标并不准确,迫切需要新的生物标志物来帮助识别
病人处于危险之中。在缺乏新工具的情况下,侵袭性真菌感染的管理仍然显著
很有挑战性。这项研究的长期目标是设计新的工具并验证新的指标估计
造血干细胞移植患者发生侵袭性真菌感染的风险。实现这一目标需要关注中性粒细胞。
蜂群功能,这是有效的抗真菌免疫反应的关键。蜂拥而至有别于
吞噬作用,因为它涉及中性粒细胞-中性粒细胞的通讯,帮助协调
多个细胞向阻断侵袭性真菌的生长。对中性粒细胞聚集的关注是合理的,因为
初步结果显示,在HSCT患者中,即使中性粒细胞计数在4周后恢复
移植后,中性粒细胞聚集缺陷仍然存在,而且是严重的。关于中性粒细胞如何
在目前缺乏HSCT后,随着时间的推移,集群缺陷会得到解决。为了解决这一知识差距,并
评估新生物标志物的效用我们将追求以下具体目标:1)测定中性粒细胞
在健康患者和造血干细胞移植患者中不同的群集性参数。2)确定哪些细胞因子有助于修复
造血干细胞移植患者中性粒细胞的聚集活性及3)设计新的无标记成像技术
人体中性粒细胞对显微组织损伤的体内反应。如果成功,建议的
研究可以通过改善对HSCT患者康复的监测来对他们的生活产生重大影响
并通过确定加速中性粒细胞功能恢复的潜在策略和改善
它们对真菌感染的保护。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Daniel Irimia其他文献
Daniel Irimia的其他文献
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