Division of Oncology/Blood and Marrow Transplantation, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Biol Blood Marrow Transplant. 2013 Nov;19(11):1566-73. doi: 10.1016/j.bbmt.2013.07.025. Epub 2013 Aug 2.
Transplantation of bone marrow cells leads to engraftment of osteopoietic and hematopoietic progenitors. We sought to determine whether the recently described transient expansion of the host osteoblastic niche after marrow radioablation promotes engraftment of both osteopoietic and hematopoietic progenitor cells. Mice infused with marrow cells 24 hours after total body irradiation (TBI) demonstrated significantly greater osteopoietic and hematopoietic progenitor chimerism than did mice infused at 30 minutes or 6 hours. Irradiated mice with a lead shield over 1 hind limb showed greater hematopoietic chimerism in the irradiated limb than in the shielded limb at both the 6- and 24-hour intervals. By contrast, the osteopoietic chimerism was essentially equal in the 2 limbs at each of these intervals, although it significantly increased when cells were infused 24 hours compared with 6 hours after TBI. Similarly, the number of donor phenotypic long-term hematopoietic stem cells was equivalent in the irradiated and shielded limbs after each irradiation-to-infusion interval but was significantly increased at the 24-hour interval. Our findings indicate that a 24-hour delay in marrow cell infusion after TBI facilitates expansion of the endosteal osteoblastic niche, leading to enhanced osteopoietic and hematopoietic engraftment.
骨髓细胞移植导致成骨和造血祖细胞的植入。我们试图确定骨髓放射消融后最近描述的宿主成骨细胞龛的短暂扩张是否促进成骨和造血祖细胞的植入。与在照射后 30 分钟或 6 小时输注骨髓细胞的小鼠相比，在全身照射（TBI）后 24 小时输注骨髓细胞的小鼠表现出明显更高的成骨和造血祖细胞嵌合体。在一条后腿上有铅屏蔽的照射小鼠在 6 小时和 24 小时间隔时，照射肢的造血嵌合体明显高于屏蔽肢。相比之下，在这些间隔的每一个时间点，2 条腿的成骨嵌合体基本相等，尽管与 TBI 后 6 小时相比，在 24 小时后输注时显著增加。同样，在每次照射至输注间隔后，照射和屏蔽肢体中的供体表型长期造血干细胞数量相等，但在 24 小时间隔时显著增加。我们的发现表明，TBI 后骨髓细胞输注延迟 24 小时可促进骨内膜成骨细胞龛的扩张，从而增强成骨和造血植入。
