Shirvaikar Neeta, Marquez-Curtis Leah A, Janowska-Wieczorek Anna
Research & Development, Canadian Blood Services, 8249 114th Street NW, Edmonton, AB, Canada T6G 2R8.
Biochem Res Int. 2012;2012:685267. doi: 10.1155/2012/685267. Epub 2012 Mar 4.
Hematopoietic stem/progenitor cells (HSPCs) are used in clinical transplantation to restore hematopoietic function. Here we review the role of the soluble matrix metalloproteinases MMP-2 and MMP-9, and membrane type (MT)1-MMP in modulating processes critical to successful transplantation of HSPC, such as mobilization and homing. Growth factors and cytokines which are employed as mobilizing agents upregulate MMP-2 and MMP-9. Recently we demonstrated that MT1-MMP enhances HSPC migration across reconstituted basement membrane, activates proMMP-2, and contributes to a highly proteolytic bone marrow microenvironment that facilitates egress of HSPC. On the other hand, we reported that molecules secreted during HSPC mobilization and collection, such as hyaluronic acid and thrombin, increase MT1-MMP expression in cord blood HSPC and enhance (prime) their homing-related responses. We suggest that modulation of MMP-2, MMP-9, and MT1-MMP expression has potential for development of new therapies for more efficient mobilization, homing, and engraftment of HSPC, which could lead to improved transplantation outcomes.
造血干/祖细胞（HSPCs）被用于临床移植以恢复造血功能。在此，我们综述可溶性基质金属蛋白酶MMP-2和MMP-9以及膜型（MT）1-MMP在调节对HSPC成功移植至关重要的过程（如动员和归巢）中的作用。用作动员剂的生长因子和细胞因子会上调MMP-2和MMP-9。最近我们证明，MT1-MMP可增强HSPC跨重组基底膜的迁移，激活前MMP-2，并促成一个高度蛋白水解的骨髓微环境，有利于HSPC的迁出。另一方面，我们报道，在HSPC动员和采集过程中分泌的分子，如透明质酸和凝血酶，可增加脐带血HSPC中MT1-MMP的表达，并增强（启动）其与归巢相关的反应。我们认为，调节MMP-2、MMP-9和MT1-MMP的表达有可能开发出新的疗法，以更有效地动员、归巢和植入HSPC，从而改善移植结果。
