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造血干细胞的鉴定、分离及其诱导供体特异性移植耐受和治疗自身免疫性疾病能力的起源。

The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases.

作者信息

Weissman Irving L, Shizuru Judith A

机构信息

Stanford Institute of Stem Cell Biology and Regenerative Medicine, Stanford, CA 94304-1334, USA.

出版信息

Blood. 2008 Nov 1;112(9):3543-53. doi: 10.1182/blood-2008-08-078220.

Abstract

Advances in the understanding of the cells of the hematopoietic system have provided a rich basis for improving clinical hematopoietic cell transplants; finding and using proteins and molecules to amplify or suppress particular blood cell types; understanding the stepwise progression of preleukemic stages leading first to chronic myeloid disorders, then the emergence of acute blastic leukemias; and treating malignant and nonmalignant diseases with cell subsets. As a result of intense scientific investigation, hematopoietic stem cells (HSCs) have been isolated and their key functional characteristics revealed-self-renewal and multilineage differentiation. These characteristics are now found to be present in all tissue/organ stem cell studies, and even in the analysis of pluripotent embryonic, nuclear transfer, and induced pluripotent stem cells. Studies on HSC have identified hematopoiesis as one of the best systems for studying developmental cell lineages and as the best for understanding molecular changes in cell fate decision-making and for finding preclinical and clinical platforms for tissue and organ replacement, regeneration, and oncogenesis. Here we review the steps, from our viewpoint, that led to HSC isolation and its importance in self-nonself immune recognition.

摘要

对造血系统细胞认识的进展为改善临床造血细胞移植提供了丰富的基础;发现并利用蛋白质和分子来扩增或抑制特定血细胞类型;理解白血病前期阶段的逐步进展,该阶段首先导致慢性骨髓疾病,随后急性原始细胞白血病的出现;以及用细胞亚群治疗恶性和非恶性疾病。经过深入的科学研究,造血干细胞(HSC)已被分离出来,其关键功能特性——自我更新和多谱系分化也已被揭示。现在发现这些特性存在于所有组织/器官干细胞研究中,甚至在多能胚胎、核移植和诱导多能干细胞的分析中也存在。对造血干细胞的研究已将造血作用确定为研究发育细胞谱系的最佳系统之一,也是理解细胞命运决定中的分子变化以及寻找组织和器官替代、再生及肿瘤发生的临床前和临床平台的最佳系统。在此,我们从我们的视角回顾导致造血干细胞分离的步骤及其在自身-非自身免疫识别中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ed2/2574516/a4629729a4b9/zh80240827420002.jpg

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