The potential for the use of mononuclear cells from human umbilical cord blood in the treatment of amyotrophic lateral sclerosis in SOD1 mice.
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.
Chen
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Department of Pathology and Laboratory Medicine, New Jersey School of Medicine, University of Medicine and Dentistry, Newark 07103, USA.
Ende
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D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D000818:Animals; D016026:Bone Marrow Transplantation; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D017708:Leukocyte Transfusion / Q000379:methods*; D007963:Leukocytes, Mononuclear; D051379:Mice; D008822:Mice, Transgenic; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000401:mortality; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D015996:Survival Rate; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic; D014916:Whole-Body Irradiation
D017931:DNA Primers; D004247:DNA; D013482:Superoxide Dismutase