HUMAN UMBILICAL-CORD BLOOD - A CLINICALLY USEFUL SOURCE OF TRANSPLANTABLE HEMATOPOIETIC STEM PROGENITOR CELLS

HUMAN UMBILICAL-CORD BLOOD - A CLINICALLY USEFUL SOURCE OF TRANSPLANTABLE HEMATOPOIETIC STEM PROGENITOR CELLS
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DOI:
10.1002/stem.5530080708
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发表时间:
1990-01-01
期刊:
INTERNATIONAL JOURNAL OF CELL CLONING
影响因子:
--
通讯作者:
BOYSE, EA
BOYSE, EA
中科院分区:
其他
文献类型:
--
作者:
BROXMEYER, HE;GLUCKMAN, E;BOYSE, EA

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这是一个审查和讨论的研究,导致第一次使用人脐带血,材料通常被丢弃,为临床造血重建提供干/祖细胞[1,2]。这一前景的出现是由于对脐带血的收获和冷冻保存及其在体外可证明的祖细胞的数量含量的广泛研究。一名男性患者范可尼贫血(FA)的条件与修改方案的环磷酰胺和辐射,适应异常高的敏感性,这些代理的特点是FA。在出生时从产前检查中已知不受FA影响且与预期同胞受体人类白细胞抗原(HLA)相容的女性同胞中提取冷冻保存的脐带血。在解冻脐带血的调节和治疗性输注后,成功的造血重建由患者的一般健康状况、满意的血液学标准和骨髓中各种类型的造血祖细胞计数来指示,该患者先前需要支持性输血。从细胞遗传学、ABO分型、DNA多态性研究和正常细胞对细胞毒性药物的耐药性(显示FA细胞的脆弱性)中可以明显看出,骨髓系统与供体细胞完全植入;血液中含有表现出染色体损伤的宿主淋巴细胞残留物,但趋势是消除这些受损细胞。这意味着来自单个个体的脐带血应该为自体或HLA相容的同种异体受体的有效造血重建提供足够的重建细胞。
This is a review and discussion of studies leading to the first use of human umbilical cord blood, material usually discarded, for the provision of stem/progenitor cells for clinical hematopoietic reconstitution [1,2]. This prospect arose as a result of extensive studies of the harvesting and cryopreservation of cord blood and of its numerical content of progenitor cells demonstrable in vitro. A male patient with Fanconi anemia (FA) was conditioned with a modified regimen of cyclophosphamide and irradiation that accommodates the abnormally high sensitivity to these agents that is characteristic of FA. Cryopreserved cord blood had been retrieved at birth from a female sibling known from prenatal testing to be unaffected by FA and to be human leukocyte antigen (HLA)‐compatible with the prospective sibling recipient. After conditioning and therapeutic infusion of thawed cord blood, successful hematopoietic reconstitution was indicated by the general health of the patient, who had previously required supportive transfusions, by satisfactory hematological criteria and by counts of hematopoietic progenitor cells of various types in the bone marrow. Complete engraftment of the myeloid system with donor cells was evident from cytogenetics, ABO typing, study of DNA polymorphisms, and normal cellular resistance to cytotoxic agents that reveal the fragility of FA cells; the blood contained a residuum of host lymphocytes exhibiting chromosomal damage, but the trend has been towards eliminating these damaged cells. This implies that cord blood from a single individual should provide sufficient reconstituting cells for effective hematopoietic repopulation of an autologous or an HLA‐compatible allogeneic recipient.