Szilvassy Stephen J
Hematology, Amgen Inc, Thousand Oaks, CA 91320, USA.
Arch Med Res. 2003 Nov-Dec;34(6):446-60. doi: 10.1016/j.arcmed.2003.06.004.
Rarely has so much interest from the lay public, government, biotechnology industry, and special interest groups been focused on the biology and clinical applications of a single type of human cell as is today on stem cells, the founder cells that sustain many, if not all, tissues and organs in the body. Granting organizations have increasingly targeted stem cells as high priority for funding, and it appears clear that the evolving field of tissue engineering and regenerative medicine will require as its underpinning a thorough understanding of the molecular regulation of stem cell proliferation, differentiation, self-renewal, and aging. Despite evidence suggesting that embryonic stem (ES) cells might represent a more potent regenerative reservoir than stem cells collected from adult tissues, ethical considerations have redirected attention upon primitive cells residing in the bone marrow, blood, brain, liver, muscle, and skin, from where they can be harvested with relative sociological impunity. Among these, it is arguably the stem and progenitor cells of the mammalian hematopoietic system that we know most about today, and their intense study in rodents and humans over the past 50 years has culminated in the identification of phenotypic and molecular genetic markers of lineage commitment and the development of functional assays that facilitate their quantitation and prospective isolation. This review focuses exclusively on the biology of hematopoietic stem cells (HSCs) and their immediate progeny. Nevertheless, many of the concepts established from their study can be considered fundamental tenets of an evolving stem cell paradigm applicable to many regenerating cellular systems.
普通大众、政府、生物技术产业以及特殊利益集团对单一类型人类细胞的生物学特性和临床应用所表现出的浓厚兴趣,很少能像如今对干细胞这般强烈。干细胞是维持人体许多(即便不是全部)组织和器官的起始细胞。资助机构越来越将干细胞列为资金投入的高度优先领域,而且很明显,不断发展的组织工程和再生医学领域将需要以深入理解干细胞增殖、分化、自我更新和衰老的分子调控作为其基础。尽管有证据表明胚胎干细胞可能比从成体组织收集的干细胞具有更强的再生能力储备,但伦理考量已将注意力重新转向存在于骨髓、血液、大脑、肝脏、肌肉和皮肤中的原始细胞,从这些部位采集它们相对不会引发社会争议。其中,目前我们了解最多的大概是哺乳动物造血系统的干细胞和祖细胞,在过去50年里对它们在啮齿动物和人类身上的深入研究,最终确定了细胞谱系定向的表型和分子遗传标记,并开发出有助于对它们进行定量和前瞻性分离的功能检测方法。本综述专门聚焦于造血干细胞(HSCs)及其直接子代的生物学特性。然而,从对它们的研究中确立的许多概念可被视为适用于许多再生细胞系统的不断发展的干细胞范式的基本原理。