作为造血系统的看护人,造血干细胞确保终身供应负责关键身体功能的分化群体,包括氧气运输,免疫保护和凝血。由于造血系统的深远影响,血液病通常会对个体的生活产生重大影响,甚至变得致命。造血细胞移植是治疗此类血液病的第一个有效的治疗途径。从那以后,造血干细胞在治疗中的关键使用和操作一直渴望充分利用如此重要的细胞群。对造血干细胞行为的有限知识激发了对其生物学的深入研究。努力能够揭示其在发育和成年阶段的原始环境和特征。细胞水平的几个信号通路已经被定位,提供对他们机器的洞察。随着对造血干细胞代谢和进行性衰老的理解的提高,人们开始理解造血干细胞维持的重要动态。这些进展为开发造血干细胞操作的创新策略提供了坚实的平台。具体来说,造血干细胞池的扩大引发了巨大的兴趣,获得动力。各种各样的方法已经萌芽,导致各种扩展系统,从更简单的基于小分子的策略到复杂的仿生支架。最近Omisirge的批准,第一个扩增的造血干细胞和祖细胞产品,其扩展平台是最早的扩展平台之一,预示着可能很快会出现的进一步成功。为了保证这些离体操作细胞的质量,需要开发测量细胞功能或效力的强大测定法。是否靶向造血植入,免疫分化潜力或恶性肿瘤清除,造血干细胞及其衍生物需要有效扩大其治疗效力。在这次审查中,我们全面地将造血干细胞视为治疗资产,从基础到翻译。
As caretakers of the hematopoietic system, hematopoietic stem cells assure a lifelong supply of differentiated populations that are responsible for critical bodily functions, including oxygen transport, immunological protection and coagulation. Due to the far-reaching influence of the hematopoietic system, hematological disorders typically have a significant impact on the lives of individuals, even becoming fatal. Hematopoietic cell transplantation was the first effective therapeutic avenue to treat such hematological diseases. Since then, key use and manipulation of hematopoietic stem cells for treatments has been aspired to fully take advantage of such an important cell population. Limited knowledge on hematopoietic stem cell behavior has motivated in-depth research into their biology. Efforts were able to uncover their native environment and characteristics during development and adult stages. Several signaling pathways at a cellular level have been mapped, providing insight into their machinery. Important dynamics of hematopoietic stem cell maintenance were begun to be understood with improved comprehension of their metabolism and progressive aging. These advances have provided a solid platform for the development of innovative strategies for the manipulation of hematopoietic stem cells. Specifically, expansion of the hematopoietic stem cell pool has triggered immense interest, gaining momentum. A wide range of approaches have sprouted, leading to a variety of expansion systems, from simpler small molecule-based strategies to complex biomimetic scaffolds. The recent approval of Omisirge, the first expanded hematopoietic stem and progenitor cell product, whose expansion platform is one of the earliest, is predictive of further successes that might arise soon. In order to guarantee the quality of these ex vivo manipulated cells, robust assays that measure cell function or potency need to be developed. Whether targeting hematopoietic engraftment, immunological differentiation potential or malignancy clearance, hematopoietic stem cells and their derivatives need efficient scaling of their therapeutic potency. In this review, we comprehensively view hematopoietic stem cells as therapeutic assets, going from fundamental to translational.