Several points in the Uchida paper are of interest:

1) The low proliferation rate of 5-7 percent of the human cells after transplantation suggests that these stem cells are generating more progeny and may provide more oligodendrocytes over time. The problem with the shiverer mouse model is that the mice do not live long enough to do behavioral studies after transplantation and to assess the extent of continuous production of myelinating cells. The data presented suggest that these cells are a good source for myelin producing oligodendrocytes.

Several points in the Uchida paper are of interest:

1) The low proliferation rate of 5-7 percent of the human cells after transplantation suggests that these stem cells are generating more progeny and may provide more oligodendrocytes over time. The problem with the shiverer mouse model is that the mice do not live long enough to do behavioral studies after transplantation and to assess the extent of continuous production of myelinating cells. The data presented suggest that these cells are a good source for myelin producing oligodendrocytes.

One worry on everyone’s mind is always whether these cell will proliferate in an uncontrolled manner to produce tumors. It appears from these and other studies using these HuCNS cells that this is not the case, which is critical for human trials.

2) It is very interesting that the human cells appear to be responding to the same signals as the endogenous mouse cells by proliferating and making more healthy human oligodendrocytes. This suggests that the signals originating in the diseased brain to make more myelin producing cells are interpreted in a similar fashion by both human and mouse oligodendrocytes. What is really interesting is that the human stem cells seem to prefer to differentiate into predominantely myelin producing oligodendrocytes over the production of neurons and glial cells. This results in the generation of the needed cell type and minimizes the appearance of the “wrong” cell types.

The clinical study by Rowitch’s group shows that these human HuCNS-SCs can be transplanted into young human brains and engraft. There does not appear to be any overgrowth of transplanted cells, thus minimizing the concern of tumor formation. The data using magnetic resonance imaging methods suggest that these cells are contributing to the generation of new myelin in and around the transplantation sites. It does not appear that the cells migrate as extensively in the human brain as they do in the rodent brain, which is consistent with many other transplant studies that compare the migration of human cells and rodent cells. Human cells can migrate great distances in the rodent brain. Whether this is true in the human brain is less certain.