Deans R J, Moseley A B
Osiris Therapeutics, Baltimore, MD 21231, USA.
Exp Hematol. 2000 Aug;28(8):875-84. doi: 10.1016/s0301-472x(00)00482-3.
There has been an increasing interest in recent years in the stromal cell system functioning in the support of hematopoiesis. The stromal cell system has been proposed to consist of marrow mesenchymal stem cells that are capable of self-renewal and differentiation into various connective tissue lineages. Recent efforts demonstrated that the multiple mesenchymal lineages can be clonally derived from a single mesenchymal stem cell, supporting the proposed paradigm. Dexter demonstrated in 1982 that an adherent stromal-like culture was able to support maintenance of hematopoietic stem as well as early B lymphopoeisis. Recent data from in vitro models demonstrating the essential role of stromal support in hematopoiesis shaped the view that cell-cell interactions in the marrow microenvironment are critical for normal hematopoietic function and differentiation. Maintenance of the hematopoietic stem cell population has been used to increase the efficiency of hematopoietic stem cell gene transfer. High-dose chemotherapy and frequently cause stromal damage with resulting hematopoietic defects. Data from preclinical transplantation studies suggested that stromal cell infusions not only prevent the occurrence of graft failure, but they have an immunomodulatory effect. Preclinical and early clinical safety studies are paving the way for further applications of mesenchymal stem cells in the field of transplantation with respect to hematopoietic support, immunoregulation, and graft facilitation.
近年来,人们对支持造血功能的基质细胞系统的兴趣与日俱增。有人提出,基质细胞系统由能够自我更新并分化为各种结缔组织谱系的骨髓间充质干细胞组成。最近的研究表明,多个间充质谱系可以从单个间充质干细胞克隆衍生而来,这支持了上述范例。1982年,德克斯特证明,一种贴壁的基质样培养物能够支持造血干细胞的维持以及早期B淋巴细胞生成。来自体外模型的最新数据表明,基质支持在造血过程中起着至关重要的作用,这使人们形成了这样一种观点,即骨髓微环境中的细胞间相互作用对于正常造血功能和分化至关重要。维持造血干细胞群体已被用于提高造血干细胞基因转移的效率。高剂量化疗经常会导致基质损伤,进而造成造血缺陷。临床前移植研究的数据表明,输注基质细胞不仅可以预防移植失败的发生,而且还具有免疫调节作用。临床前和早期临床安全性研究正在为间充质干细胞在移植领域进一步应用于造血支持、免疫调节和移植促进方面铺平道路。