HUMAN UMBILICAL-CORD BLOOD AS A POTENTIAL SOURCE OF TRANSPLANTABLE HEMATOPOIETIC STEM PROGENITOR CELLS
HUMAN UMBILICAL-CORD BLOOD AS A POTENTIAL SOURCE OF TRANSPLANTABLE HEMATOPOIETIC STEM PROGENITOR CELLS
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DOI：
10.1073/pnas.86.10.3828
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
BOYSE, EA
中科院分区：
文献类型：
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作者：
BROXMEYER, HE;DOUGLAS, GW;BOYSE, EA
本研究的目的是评价人脐带血作为骨髓替代品在造血重建中提供可移植干/祖细胞的作用。虽然目前还没有直接定量测定人造血再生细胞，但粒细胞-巨噬细胞祖细胞（CFU-GM）测定已成功用作移植能力的有效指标。我们检查了> 100份人脐带血的有核细胞和粒细胞-巨噬细胞、红系（BFU-E）和多能（CFU-GEMM）祖细胞的含量，在许多情况下，在冷冻保存前后都是如此。首先，确定粒细胞-巨噬细胞、红细胞和多能祖细胞在未处理的脐带血中保持功能活性，除了在4 ℃下加入抗凝剂至少3天。C或25 ℃。C（室温），但不是在37 ℃。C，这意味着这些细胞可以令人满意的研究和使用或冷冻保存后的脐带血运输的远程产科服务的隔夜空运运输治疗。粒细胞-巨噬细胞祖细胞从脐带血收到正常反应的刺激纯化重组制剂的粒细胞-巨噬细胞，粒细胞，巨噬细胞集落刺激因子和白细胞介素3。基于对101份脐带血采集物的分析，显著的发现是在Ficoll/Hypaque分离后存在于低密度（< 1.077 gm/ml）部分中的祖细胞数量通常落在已报道的骨髓细胞成功植入的范围内。另一个具有实际重要性的观察结果是，在冷冻前去除红细胞或粒细胞，以及在接种前洗涤解冻的细胞的程序，导致祖细胞的大量损失，来自未分级脐带血的未洗涤祖细胞的产量要高出许多倍。初步推断，来自单个个体的人脐带血通常是自体（同基因）和主要组织相容性复合物匹配的同种异体造血重建的足够细胞来源。
The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstituiton. Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability. We examined > 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation. First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4.degree. C or 25.degree. C (room temperature), though not at 37.degree. C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service. Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3. The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (< 1.077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells. Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater. The provisional inference is that human umibilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution.