Transplantation of embryonic stem cells and their neural derivatives can
lead to amelioration of the disease symptoms of experimental autoimmune
encephalomyelitis (EAE), an animal model for multiple sclerosis
(MS). Oligodendroglial progenitors (OPs), derived from human embryonic
stem cells (hESC, HES-1), were labeled with superparamagnetic iron oxide
and transduced with luciferase. At 7 days following induction of EAE in
C57/BL6 mice, 1×10(6) cells were transplanted in the ventricles of
C57/BL6 mice and non-invasively monitored by magnetic resonance and
bioluminescence imaging. Cells were found to remain within the
cerebroventricular system and did not survive for more than 10 days.
However, EAE mice that received hESC-OPs showed a significant
improvement in neurological disability scores (0.9±0.2; n=12) compared
to that of control animals (3.3±0.4; n=12) at day 15
post-transplantation. Histopathologically, transplanted hESC-OPs
generated TREM2-positive CD45 cells, increased TIMP-1 expression,
confined inflammatory cells within the subarachnoid space, and gave rise
to higher numbers of Foxp3-positive regulatory T cells in the spinal
cord and spleen. Our results suggest that transplantation of hESC-OPs
can alter the pathogenesis of EAE through immunomodulation, potentially
providing new avenues for stem cell-based treatment of MS.
Human stem cells were used to generate immature oligodendrocytes and these were transplanted into the brain of mice with EAE after they had been made to contain some iron particles so that they could be tracked. After they were injected they stayed where they are and were dead within two weeks. The did not convert into to myelinating cells or nerves that the hype would leave us to believe. Were they rejected by the mouse,s immune system that would mean they would be quickly killed? ...well possibly. They generated macrophage-like cells, but they were probably there to clear up the dead transplanted cells.
Their major benefit was that they appearred to modulate the immune response. These would therefore affect relapsing disease. This is why people involved in early trials with mesenchymal stem cells are being selected to be relapsing even if they have progressive MS.
We know that there are immature oligodendrocytes in the lesions of MS but they are not myelinating, so we need to change the environment such that it is conducive to repair. Is it missing the X factor?