Kiss-and-Tell: Transgenes Reveal Embryonic Stem Cell Promiscuity

Abstract

Transplanted bone marrow derived stem cells (BMDCs) have been shown to be highly fusionogenic with Purkinje cells of the cerebellum. Damage to the brain or irradiation amplify the number of fusion events. To date, no report of fusion between transplanted embryonic stem cells (ESCs), or their derivatives, and neurons has been reported. We have transplanted ESCs into two models of neurological disease and have found clear evidence of fusion between the donor and host cells. The ESCs are genetically engineered to produce the LacZ gene, which can be detected using a histochemical stain that provides a royal blue precipitate in the stem cells or their derivatives. After transplanting our cells into the striatum, we found blue precipitate in the Purkinje cells of the cerebellum, in the brainstem, and in the cerebral cortex. While many reports using BMDCs show cell fusion and stable heterokaryons after transplantation, our histochemistry and electron microscopy data do not display binucleation, indicating no stable nuclear fusion. The blue precipitate and lack of binucleation suggests that the transplanted embryonic stem cells are not fusing, but undergoing transient contact with the target cells: the ?kiss.? This interpretation is consistent with recent reports of partial cell fusion of stem cells through the transient formation of nanotubes. This issue will need to be thoroughly explored to fully understand the potential, and the limitations, of eventual stem cell therapies for the central nervous system.