Chen R, Ende N
Department of Pathology and Laboratory Medicine, New Jersey School of Medicine, University of Medicine and Dentistry, Newark 07103, USA.
J Med. 2000;31(1-2):21-30.
The SOD1 mice (transgenic B6SJL-TgN(SOD1-G93A)1GUR) have a mutation of the human transgene (CuZn superoxide dismutase gene SOD1) that has been associated with amyotrophic lateral sclerosis (ALS). In a preliminary study, we demonstrated that a megadose of human umbilical cord blood mononuclear cells given intravenously after 800 cGy of irradiation could substantially increase the life span of SOD1 mice. This report is an attempt to confirm and expand the preliminary findings. By repeating the study and raising the number of human cord blood cells from 33.2-34.0 x 10(6) to 70.2-73.3 x 10(6) there was a further significant increase in the life span of the SOD1 mice. The average life of the controls was 123.5 days while that of mice receiving the larger megadose of cells was 162 days. While all the controls were dead by 130 days, the treated group receiving 70.2-73.3 x 10(6) cells had one animal living up to 187 days and one 210 days. In order to obtain a megadose of cells, pooled blood from different donors was used and did not appear to have a negative effect, but indicated a beneficial effect on survival. The clinical significance of these findings may extend beyond the potential treatment for amyotrophic lateral sclerosis. This study confirms and extends the preliminary study whereby increasing the dose of human umbilical cord blood cells we were able to substantially further increase the survival of SOD1 mice.
SOD1小鼠（转基因B6SJL-TgN(SOD1-G93A)1GUR）具有与肌萎缩侧索硬化症（ALS）相关的人类转基因（铜锌超氧化物歧化酶基因SOD1）突变。在一项初步研究中，我们证明在800 cGy照射后静脉注射大剂量人脐带血单个核细胞可显著延长SOD1小鼠的寿命。本报告旨在证实并扩展初步研究结果。通过重复该研究并将人脐带血细胞数量从33.2 - 34.0×10⁶增加到70.2 - 73.3×10⁶，SOD1小鼠的寿命进一步显著延长。对照组的平均寿命为123.5天，而接受更大剂量细胞的小鼠平均寿命为162天。所有对照组在130天前均死亡，而接受70.2 - 73.3×10⁶个细胞的治疗组有一只小鼠活到了187天，另一只活到了210天。为了获得大剂量的细胞，使用了来自不同供体的混合血液，这似乎没有负面影响，反而显示出对生存有有益影响。这些发现的临床意义可能超出肌萎缩侧索硬化症的潜在治疗范围。本研究证实并扩展了初步研究，即通过增加人脐带血细胞的剂量，我们能够进一步显著提高SOD1小鼠的存活率。
