Hirschi K K, Goodell M A
Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Center for Cell and Gene Therapy, Houston, TX 77030, USA.
Gene Ther. 2002 May;9(10):648-52. doi: 10.1038/sj.gt.3301722.
Bone marrow contains many cell types, including stroma, vascular cells, adipocytes, osteoblasts and osteoclasts, as well as mesenchymal stem cells and hematopoietic stem cells. It was previously thought that cells within bone marrow solely functioned to regenerate cells within the marrow, as well as all circulating hematopoietic cells in peripheral blood. Recent reports, however, suggest that marrow-derived cells can also regenerate other cell types, including cardiac muscle, liver cell types, neuronal and non-neuronal cell types of the brain, as well as endothelial cells and osteoblasts. These multiple cell types could have originated from either of the stem cell populations within bone marrow or potentially other precursors. Therefore, it is not entirely clear whether each of these distinct cell lineages has a true progenitor within marrow or whether the marrow contains a multipotent population of cells that has been set aside during embryogenesis for postnatal repair and remodeling of a variety of tissues. It is clear, however, that directing the fate of bone marrow-derived progenitors (ie toward hematopoietic, vascular or cardiac cell fates) can only be accomplished if the phenotype of the stem cells is defined, and their homing and differentiation programs are elucidated. Much work is focused on these issues, wherein lie the key to harnessing the potential of adult stem cells for autologous cell and gene therapy.
骨髓包含多种细胞类型,包括基质细胞、血管细胞、脂肪细胞、成骨细胞和破骨细胞,以及间充质干细胞和造血干细胞。以前人们认为,骨髓中的细胞仅起到再生骨髓内细胞以及外周血中所有循环造血细胞的作用。然而,最近的报告表明,骨髓来源的细胞还可以再生其他细胞类型,包括心肌、肝细胞类型、脑内的神经元和非神经元细胞类型,以及内皮细胞和成骨细胞。这些多种细胞类型可能源自骨髓内的任何一种干细胞群体,也可能源自其他前体细胞。因此,目前尚不完全清楚这些不同的细胞谱系是否在骨髓中有真正的祖细胞,或者骨髓是否包含一群在胚胎发育过程中被保留下来用于出生后各种组织修复和重塑的多能细胞。然而,很明显,只有明确干细胞的表型,并阐明它们的归巢和分化程序,才能引导骨髓来源的祖细胞的命运(即朝着造血、血管或心脏细胞命运发展)。许多工作都集中在这些问题上,而这些问题正是利用成体干细胞进行自体细胞和基因治疗潜力的关键所在。