Human umbilical cord blood effect on sod mice (amyotrophic lateral sclerosis)

In previous studies we observed that human umbilical cord blood (HUCB) coul d 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 simil ar to human lupus. We believed a temporary xenograph may have occurred in t hese animals with the disease process delayed and the life span markedly in creased. 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, h owever, maintains a significant number of cells capable of producing replat able 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 h uman transgene, (CuZn superoxide dismutase gene SOD1) that has been associa ted with amyotrophic lateral sclerosis. We previously developed evidence th at the survival of lethally irradiated mice was related to the number of hu man mononuclear cells administered. In the present study, we decided to inv estigate the effect of a relatively large dose of human mononuclear cord bl ood cells on SOD1 mice subjected to a sublethal dose of irradiation precede d by antikiller sera (rabbit anti-asialo). The SOD1 mice show evidence of p aralysis at 4 to 5 months. The average expected lifetime of these mice is r eported to be 130 days (Jackson Laboratory). In this experiment, there were 23 mice. Two mice died before the onset of paralysis. The remainder were d ivided into three groups: group I: control group of 4 unheated mice; group II: an experimental,group of 6 mice treated with antikiller sera, 800 cGy i rradiation plus 5 X 10(6) cogenic bone marrow mononuclear cells; group III: another experimental group of 11 mice treated with antikiller sera, 800 cG y irradiation plus 34.2-35.6 X 10(6) HUCB mononuclear cells, previously sto red for 17-20 days at 4 degrees C in gas permeable bags. The results were a s follows: the average age at death was: (I) 127 days for the untreated con trol group, (II) 138 days for the group that received 800 cGy of irradiatio n and cogenic bone marrow (BM) and (III) 148 days for the group that receiv ed 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 re spectively. In summary, large doses of HUCB mononuclear cells produced cons iderable delay in the onset of symptoms and death of SOD1 mice. These preli minary results may not only indicate that amyotrophic lateral sclerosis is an autoimmune disease, but may also indicate a possible treatment for a dev astating disease and possibly others. inc. All rights reserved. (C) 2000 El sevier Science.