Yoder M C, Cumming J G, Hiatt K, Mukherjee P, Williams D A
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis 46202-5210, USA.
Biol Blood Marrow Transplant. 1996 May;2(2):59-67.
This report describes the successful development of a transplantation model in which we engrafted adult murine bone marrow hematopoietic cells in congenic day-old murine pups. Newborn animals conditioned with high doses (> or = 7.0 Gy) of total-body irradiation (TBI) demonstrated severe growth retardation and untoward effects on the developing central nervous system. Newborn pups conditioned with a sublethal dose (5.0 Gy) of TBI, however, achieved normal growth and development up to 6 months posttransplantation, and donor type hematopoietic cell reconstitution exceeded 50% in these animals. A second conditioning regimen, comprising one or two doses of busulfan (15 mg/kg) administered intrapartum, resulted in significant myelosuppression in untransplanted newborn pups. This second regimen was associated, however, with engraftment and full multilineage reconstitution of the conditioned newborn recipient animals with adult bone marrow cells, and the engrafted pups grew and developed without apparent defect. A third conditioning regimen combining a single dose of busulfan with sublethal TBI also permitted engraftment and full multilineage reconstitution of the recipient animals. Thus, successful transplantation of hematopoietic cells into newborn recipient mice may be achieved without significant morbidity if a specific conditioning regimen is employed.
本报告描述了一种移植模型的成功构建，即在同基因新生小鼠幼崽中植入成年小鼠骨髓造血细胞。接受高剂量（≥7.0 Gy）全身照射（TBI）预处理的新生动物表现出严重的生长发育迟缓以及对发育中的中枢神经系统产生不良影响。然而，接受亚致死剂量（5.0 Gy）TBI预处理的新生幼崽在移植后6个月内实现了正常生长发育，并且这些动物体内供体类型造血细胞的重建率超过了50%。第二种预处理方案是在分娩时给予一或两剂白消安（15 mg/kg），这导致未移植的新生幼崽出现明显的骨髓抑制。然而，该第二种方案却使经预处理的新生受体动物成功植入成年骨髓细胞并实现了完全多谱系重建，且植入的幼崽生长发育未出现明显缺陷。第三种预处理方案是将单剂量白消安与亚致死剂量TBI联合使用，同样实现了受体动物的植入和完全多谱系重建。因此，如果采用特定的预处理方案，可在不产生明显发病率的情况下成功将造血细胞移植到新生受体小鼠体内。
