Human umbilical cord blood effect on sod mice (amyotrophic lateral sclerosis).
In previous studies we observed that human umbilical cord blood (HUCB) could have a protective effect on the onset of disease and time of death in MRL Lpr/Lpr mice which have an autoimmune disease that may be considered similar to human lupus. We believed a temporary xenograph may have occurred in these animals with the disease process delayed and the life span markedly increased. When HUCB is stored at 4 degrees C in gas permeable bags, there is a decrease of the cell reaction in mixed lymphocyte cultures. The blood, however, maintains a significant number of cells capable of producing replatable colonies. This study attempted to determine the effect of HUCB on SOD1 mice (transgenic B6SJL-TgN(SOD1-G93A)1GUR), which have a mutation of the human transgene, (CuZn superoxide dismutase gene SOD1) that has been associated with amyotrophic lateral sclerosis. We previously developed evidence that the survival of lethally irradiated mice was related to the number of human mononuclear cells administered. In the present study, we decided to investigate the effect of a relatively large dose of human mononuclear cord blood cells on SOD1 mice subjected to a sublethal dose of irradiation preceded by antikiller sera (rabbit anti-asialo). The SOD1 mice show evidence of paralysis at 4 to 5 months. The average expected lifetime of these mice is reported to be 130 days (Jackson Laboratory). In this experiment, there were 23 mice. Two mice died before the onset of paralysis. The remainder were divided into three groups: group I: control group of 4 untreated mice; group II: an experimental group of 6 mice treated with antikiller sera, 800 cGy irradiation plus 5 x 10(6) congenic bone marrow mononuclear cells; group III: another experimental group of 11 mice treated with antikiller sera, 800 cGy irradiation plus 34.2-35.6 x 10(6) HUCB mononuclear cells, previously stored for 17-20 days at 4 degrees C in gas permeable bags. The results were as follows: the average age at death was: (I) 127 days for the untreated control group, (II) 138 days for the group that received 800 cGy of irradiation and congenic bone marrow (BM) and (III) 148 days for the group that received irradiation and HUCB. (P < 0.001 HUCB vs control, p < 0.01 HUCB vs BM). The longest surviving mouse in each group was 131, 153, and 182 days old respectively. In summary, large doses of HUCB mononuclear cells produced considerable delay in the onset of symptoms and death of SOD1 mice. These preliminary results may not only indicate that amyotrophic lateral sclerosis is an autoimmune disease, but may also indicate a possible treatment for a devastating disease and possibly others.
Ende
N
N
Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School Newark, USA.
Weinstein
F
F
Chen
R
R
Ende
M
M
D019264:Adoptive Transfer; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000401:mortality / Q000628:therapy; 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 / Q000637:transplantation; D051379:Mice; D008822:Mice, Transgenic; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000401:mortality / Q000628:therapy; 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