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储存脐带血细胞的免疫表型和功能个体间变异性:对先进疗法的见解

Immunophenotypic and Functional Interindividual Variability in Banked Cord Blood Cells: Insights for Advanced Therapies.

作者信息

Vanegas Lozano Diana María, Devia Mejia Bellaneth, Machuca Acevedo Catalina, Jaramillo Mejia Valentina, Moreno González Andrea Marisol, Krisko Anita, Quijano Gómez Sandra Milena, Perdomo-Arciniegas Ana María

机构信息

Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud, Bogotá 111611, Colombia.

Department of Experimental Neurodegeneration, University Medical Center Gottingen, 37037 Gottingen, Germany.

出版信息

Int J Mol Sci. 2025 Jan 30;26(3):1208. doi: 10.3390/ijms26031208.

DOI:10.3390/ijms26031208
PMID:39940975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11818680/
Abstract

Umbilical cord blood (UCB) is an alternative therapeutic resource for treating both hematological and non-hematological diseases, especially for pediatric patients. However, UCB transplantation faces challenges, including delayed engraftment, increased risk of graft failure, and slower immune recovery. To maximize its clinical potential, it is essential to understand the variability and functionality of its nucleated cells. This study focused on characterizing UCB cellular populations, viability, and functionality at three key processing stages: freshly collected, post-volume reduction, and post-thawing. Using EuroFlow-based flow cytometry, significant changes were observed in granulocyte and T-cell populations during processing. Additionally, integrating EuroFlow data with hematology counts revealed variability that could affect the yield of specific cell populations, potentially influencing therapeutic decisions. An in vitro migration assay, designed to mimic the vascular niche, was employed to study donor variability in cellular migratory patterns. Notably, thawed UCB cells displayed two distinct migration profiles, distinguishing lymphocyte-like cells from monocyte-like cells. These findings underscore the importance of reproducible cellular quality control measures, such as immunophenotypic and functional donor characterization, to ensure the integrity of UCB composition. A better understanding of these parameters could improve the consistency and reliability of UCB as a starting material for the development of advanced therapies.

摘要

脐带血(UCB)是治疗血液系统疾病和非血液系统疾病的一种替代治疗资源,尤其适用于儿科患者。然而,脐带血移植面临诸多挑战,包括植入延迟、移植物失败风险增加以及免疫恢复缓慢。为了最大限度地发挥其临床潜力,了解其有核细胞的变异性和功能至关重要。本研究聚焦于在三个关键处理阶段对脐带血的细胞群体、活力和功能进行表征:刚采集时、体积减少后以及解冻后。使用基于EuroFlow的流式细胞术,在处理过程中观察到粒细胞和T细胞群体发生了显著变化。此外,将EuroFlow数据与血液学计数相结合,发现了可能影响特定细胞群体产量的变异性,这可能会影响治疗决策。采用一种旨在模拟血管微环境的体外迁移试验来研究供体在细胞迁移模式方面的变异性。值得注意 的是,解冻后的脐带血细胞呈现出两种不同的迁移模式,将淋巴细胞样细胞与单核细胞样细胞区分开来。这些发现强调了可重复的细胞质量控制措施的重要性,如免疫表型和功能性供体表征,以确保脐带血成分的完整性。更好地了解这些参数可以提高脐带血作为先进疗法开发起始材料的一致性和可靠性。

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引用本文的文献

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Monitoring Immune Responses to Vaccination: A Focus on Single-Cell Analysis and Associated Challenges.监测疫苗接种的免疫反应:聚焦单细胞分析及相关挑战
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本文引用的文献

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Development of VLA4 and CXCR4 Antagonists for the Mobilization of Hematopoietic Stem and Progenitor Cells.开发 VLA4 和 CXCR4 拮抗剂以动员造血干细胞和祖细胞。
Biomolecules. 2024 Aug 14;14(8):1003. doi: 10.3390/biom14081003.
2
Umbilical cord blood T cells can be isolated and enriched by CD62L selection for use in 'off the shelf' chimeric antigen receptor T-cell therapies to widen transplant options.脐带血T细胞可通过CD62L选择进行分离和富集,用于“现成可用”的嵌合抗原受体T细胞疗法,以拓宽移植选择。
Haematologica. 2024 Dec 1;109(12):3941-3951. doi: 10.3324/haematol.2024.285101.
3
CD14 positive cells accelerate hematopoietic stem cell engraftment.
CD14 阳性细胞可加速造血干细胞植入。
Bone Marrow Transplant. 2022 Jun;57(6):942-948. doi: 10.1038/s41409-022-01662-1. Epub 2022 Apr 8.
4
Clinical Outcomes of Unrelated Umbilical Cord Blood Graft vs. Haploidentical Donor Transplantation: Critical Issues for an Adequate Comparison.非亲属脐带血移植与单倍体供者移植的临床结局:充分比较的关键问题
Front Med (Lausanne). 2021 Oct 28;8:749810. doi: 10.3389/fmed.2021.749810. eCollection 2021.
5
Non-transplantable cord blood units as a source for adoptive immunotherapy of leukaemia and a paradigm of circular economy in medicine.非移植脐带血单位作为白血病过继免疫疗法的来源和医学循环经济的范例。
Br J Haematol. 2021 Jul;194(1):158-167. doi: 10.1111/bjh.17464. Epub 2021 May 26.
6
The wider perspective: cord blood banks and their future prospects.更广阔的视角:脐带血库及其未来前景。
Br J Haematol. 2021 Nov;195(4):507-517. doi: 10.1111/bjh.17468. Epub 2021 Apr 20.
7
Cord blood beyond transplantation: can we use the experience to advance all cell therapies?脐带血的应用不仅仅局限于移植:我们能否利用这一经验来推动所有细胞疗法的发展?
Br J Haematol. 2021 Jul;194(1):14-27. doi: 10.1111/bjh.17297. Epub 2021 Feb 2.
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The Binns Program for Cord Blood Research: A novel model of cord blood banking for academic biomedical research.宾斯脐带血研究计划:一种用于学术生物医学研究的新型脐带血库模式。
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