San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), San Raffaele Scientific Institute, Milan, 20132, Italy.
Cytometry Laboratory, San Raffaele Scientific Institute, Milan, Italy.
Cytometry A. 2017 Oct;91(10):952-965. doi: 10.1002/cyto.a.23148. Epub 2017 Jun 13.
Human hematopoiesis is a complex and dynamic system where morphologically and functionally diverse mature cell types are generated and maintained throughout life by bone marrow (BM) Hematopoietic Stem/Progenitor Cells (HSPC). Congenital and acquired hematopoietic disorders are often diagnosed through the detection of aberrant frequency or composition of hematopoietic cell populations. We here describe a novel protocol, called "Whole Blood Dissection" (WBD), capable of analyzing in a single test-tube, hematopoietic progenitors and all major mature cell lineages composing either BM or peripheral blood (PB) through a multiparametric flow-cytometry analysis. WBD allows unambiguously identifying in the same tube up to 23 different blood cell types including HSPC subtypes and all the major myeloid and lymphoid lineage compartments at different stages of maturation, through a combination of 17 surface and 1 viability cell markers. We assessed the efficacy of WBD by analyzing BM and PB samples from adult (n = 8) and pediatric (n = 9) healthy donors highlighting age-related shift in cell composition. We also tested the capability of WBD on detecting aberrant hematopoietic cell composition in clinical samples of patients with primary immunodeficiency or leukemia unveiling expected and novel hematopoietic unbalances. Overall, WBD allows unambiguously identifying >99% of the cell subpopulations composing a blood sample in a reproducible, standardized, cost-, and time-efficient manner. This tool has a wide range of potential pre-clinical and clinical applications going from the characterization of hematopoietic disorders to the monitoring of hematopoietic reconstitution in patients after transplant or gene therapy. © 2017 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC.
人类造血是一个复杂而动态的系统,其中形态和功能多样化的成熟细胞类型由骨髓(BM)造血干/祖细胞(HSPC)在整个生命过程中产生和维持。先天性和获得性造血疾病通常通过检测造血细胞群体的异常频率或组成来诊断。我们在这里描述了一种新的方案,称为“全血剖析”(WBD),能够通过多参数流式细胞术分析在单个试管中分析造血祖细胞和构成 BM 或外周血(PB)的所有主要成熟细胞谱系。WBD 通过组合使用 17 种表面和 1 种活细胞标记物,能够在同一管中明确地鉴定多达 23 种不同的血细胞类型,包括 HSPC 亚型和所有主要的骨髓和淋巴谱系,处于不同的成熟阶段。我们通过分析来自成人(n=8)和儿科(n=9)健康供体的 BM 和 PB 样本评估了 WBD 的功效,突出了细胞组成与年龄相关的变化。我们还测试了 WBD 在检测原发性免疫缺陷或白血病患者临床样本中异常造血细胞组成的能力,揭示了预期和新的造血失衡。总体而言,WBD 能够以可重复、标准化、经济高效和省时的方式明确地鉴定组成血液样本的>99%的细胞亚群。该工具具有广泛的潜在临床前和临床应用,从造血疾病的特征到移植或基因治疗后患者造血重建的监测。 2017 年作者。细胞术第 A 部分由 Wiley 期刊出版,代表 ISAC。