骨髓间充质干细胞诱导分化成骨细胞支持脐血造血干/祖细胞培养研究
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摘要
背景与目的
现代实验血液学中，体外模拟造血干祖细胞(HSPCs)在体内的生存、增殖、分化、自我更新等生理活动所需的造血微环境，探索研究造血干祖细胞体外培养和扩增的最适条件一直是倍受关注的课题。近年来的相关研究越来越清楚地认识到：成骨细胞是由间充质干细胞定向分化而来，是骨髓内造血微环境重要的细胞成分之一，是构建HSC生态位区至关重要的支撑成分，并对位居其中的造血干祖细胞细胞(HSPCs)生存、迁移、增殖、自我更新以及保持其多向分化潜能等起着关键性调控作用。造血干细胞生态位区(hematopoietic stem cells niche)是从物理空间结构和功能的角度对造血微环境进行的阐释，它主要是由成骨细胞，骨髓间充质细胞，以及类骨质(osteoid)构成的能容纳一个或更多的造血干细胞的空间结构单位，位居其间的造血干细胞通过与相邻微环境(包括成骨细胞)相互作用来调控HSC的生存，增殖，分化以及自我更新。
本研究正是基于目前对成骨细胞与造血生态位区关系的最新认识，为了探索造血干祖细胞(HSPCs)体外培养的最适条件，也有别于现有的造血干细胞培养体系，提出了将骨髓间充质干细胞诱导分化的成骨样细胞用于构建体外造血干祖细胞培养体系的设想。从而进一步求证成骨细胞在体外造血干祖细胞培养体系中的支持作用，并试图从不同的角度认识成骨细胞与造血的相互关系。本研究共设计了四个方面相互关联的实验：第一部分实验中分别由骨髓间充质干细胞，颅骨成骨细胞，及间充
Objective
Hematopoietic stem cells niches are subsets of tissues and extracellular subsets that can indefinitely house one or more Hematopoietic stem cells and control their self-renewal and progeny production in vivo. Recent studies prove that osteoblasts and their precursors derived from a common mesenchymal stem cell play a critical role in the creation of a stem cell niche and thereby regulate HSCs maintenance, proliferation, and maturation. It is the demonstration that osteoblast-expressed regulatory components that influence Hematopoietic stem cell function are likely to include cell-cell receptors, soluble and cell surface-associated cytokines, and growth factors. Each of these factors—those known and those yet to be determined—are likely influenced by mechanical, systemic (eg, PTH), and local (eg, BMPs, Ang-1) signals that regulate osteoblastic function. Furthermore, reciprocal cooperation between HSCs and osteoblasts play a profound and central role in the establishment and maintenance of the stem cell niche in the bone marrow. The Osteoblasts are a heterogeneous population, which includes
现代实验血液学中，体外模拟造血干祖细胞(HSPCs)在体内的生存、增殖、分化、自我更新等生理活动所需的造血微环境，探索研究造血干祖细胞体外培养和扩增的最适条件一直是倍受关注的课题。近年来的相关研究越来越清楚地认识到：成骨细胞是由间充质干细胞定向分化而来，是骨髓内造血微环境重要的细胞成分之一，是构建HSC生态位区至关重要的支撑成分，并对位居其中的造血干祖细胞细胞(HSPCs)生存、迁移、增殖、自我更新以及保持其多向分化潜能等起着关键性调控作用。造血干细胞生态位区(hematopoietic stem cells niche)是从物理空间结构和功能的角度对造血微环境进行的阐释，它主要是由成骨细胞，骨髓间充质细胞，以及类骨质(osteoid)构成的能容纳一个或更多的造血干细胞的空间结构单位，位居其间的造血干细胞通过与相邻微环境(包括成骨细胞)相互作用来调控HSC的生存，增殖，分化以及自我更新。
本研究正是基于目前对成骨细胞与造血生态位区关系的最新认识，为了探索造血干祖细胞(HSPCs)体外培养的最适条件，也有别于现有的造血干细胞培养体系，提出了将骨髓间充质干细胞诱导分化的成骨样细胞用于构建体外造血干祖细胞培养体系的设想。从而进一步求证成骨细胞在体外造血干祖细胞培养体系中的支持作用，并试图从不同的角度认识成骨细胞与造血的相互关系。本研究共设计了四个方面相互关联的实验：第一部分实验中分别由骨髓间充质干细胞，颅骨成骨细胞，及间充
Objective
Hematopoietic stem cells niches are subsets of tissues and extracellular subsets that can indefinitely house one or more Hematopoietic stem cells and control their self-renewal and progeny production in vivo. Recent studies prove that osteoblasts and their precursors derived from a common mesenchymal stem cell play a critical role in the creation of a stem cell niche and thereby regulate HSCs maintenance, proliferation, and maturation. It is the demonstration that osteoblast-expressed regulatory components that influence Hematopoietic stem cell function are likely to include cell-cell receptors, soluble and cell surface-associated cytokines, and growth factors. Each of these factors—those known and those yet to be determined—are likely influenced by mechanical, systemic (eg, PTH), and local (eg, BMPs, Ang-1) signals that regulate osteoblastic function. Furthermore, reciprocal cooperation between HSCs and osteoblasts play a profound and central role in the establishment and maintenance of the stem cell niche in the bone marrow. The Osteoblasts are a heterogeneous population, which includes
引文
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2 Zhang JW, Niu C, Ye L et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003; 425: 836-841.
3 Calvi LM, Adams GB, Weibrecht K W et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 2003; 425: 841-846.
4 Dora Visnijic, Zana Kalajzic, David W et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 2004; 103: 3258-3264.
5 Taichman RS, Emerson SG.. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells 1998; 16: 7-15.
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