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The
Snuggle Phenomenon: An Early Event of Potential Cell Fusion in the Brain
Previous research shows that
transplanted stem cells have the capacity to fuse with the cells of the
host, including cells within the central nervous system. In particular,
bone marrow derived stem cells (BMDCs) are fusionogenic with Purkinje
cells in the cerebellum. Complete cell fusion results in a binucleated
cell and requires the membranes of the two cells to share their
cytoplasmic constituents. To date, fusion in the brain has not been
reported after transplantation of embryonic stem cells (ESCs). However,
our laboratory transplants ESCs into targeted areas of the brain in rat
models of focal neurological disease, and we have data indicating
possible cell fusion both at the target site and elsewhere in the
brain. We use a combination of techniques including
immunohistochemistry, immunofluorescence, confocal microscopy and
electron microscopy to show evidence of an early event of potential cell
fusion, which we have termed the “Snuggle Phenomenon”; our transplanted
stem cells migrate away from the transplanted area and can be detected
in close proximity to, or within, endogenous cells. The contact enables
the membranes to interact, leading to expression of stem cell gene
(including potentially therapeutic transgenes) expression in the host
neuron. These data have important implications in the interpretation of
transplantation studies and the eventual use of stem cells for the
treatment of diseases of the central nervous system. Support provided by: Howard Hughes Medical Institute Undergraduate Science Education Grant |
