Several recent reports have tantalized us with the possibility that adult stem cells exist that can be reprogrammed to produce various tissue types, including neurons. Two similar reports in the current online edition of Nature raise doubt about that prospect, suggesting that some of these cells are actually fusing with other cells, creating hybrids.

Austin Smith and colleagues at the University of Edinburgh, Scotland, and Oxford University, England, co-cultured differentiated mouse brain cells (from embryos and from adults) with embryonic stem cells. They wound up with pluripotent cells that carry markers identifying them as descended from the mouse brain cells, but also markers specific to the embryonic stem cells. Moreover, the researchers found genetic material from both lines, indicating the new cells were hybrids.

Similarly, Naohiro Terada and associates at the University of Florida, in Gainesville, followed up on studies showing that transplanted bone marrow cells could be reprogrammed into various cell types, including neurons. They cultured adult mouse bone marrow cells together with mouse embryonic stem cells. As in the other study, what appeared to be the de-differentiation of bone marrow cells into stem cells was, in fact, the fusion of marrow and embryonic cells. Some of these hybrids contained as many as three sets of genetic material from both sources.

Echoing the cautionary comments of Smith et al., Terada et al. note that, "Contribution of cell fusion to apparently transdifferentiated cells in vivo is presently pure speculation; however, our data raise a warning to the overzealous trend in stem cell research to conclude trans-differentiation or de-differentiation of cells without careful examination of genotypes."—Hakon Heimer

ARF: Tetraploid neurons were seen in hippocampal and basal forebrain neurons Alzheimer's (Yang et al. 2001), probably because these neurons re-enter the cell cycle and duplicate their DNA. Could these tetraploid neurons also be the result of fusion between neurons and stem cells migrating to the site of neurodegeneration?
Sugaya: I think the explanation Karl Herrup made in his paper is more likely, because if the neural stem cells could spontaneously fuse to the brain cells it would be quite dangerous. We might end up having too many tumors. Though I would be open to this idea. Affected areas of AD brain produce a lot of cytokines, like IL-3, which Terada used for induction of the fusion. Anything could happen in science.


  1. These are very interesting studies. The purpose of these studies might be
    making pluripotent cells from adult stem cells by fusing them with embryonic
    stem cells. Unfortunately, tetraploid cells made tumors in Terada's study,
    which we expected. Smith's study is showing chimera formation of the fused
    cells, but the authors have to check the function of the tissue made by the
    fused cells before they conclude the functionality of the cells. They also
    failed to show multipotency in vitro. If the cells have extra genes, we
    would expect their physiology to be disturbed.

    When I inserted an extra AβPP gene into neural stem cells, they started to
    differentiate into glial cells rather than neurons. In other words, they
    might be making Down's syndrome models. Thus these lines of study may not
    help generate new material for neuroreplacement therapy for AD.

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Paper Citations

  1. . DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci. 2001 Apr 15;21(8):2661-8. PubMed.

Further Reading

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Primary Papers

  1. . Changing potency by spontaneous fusion. Nature. 2002 Apr 4;416(6880):545-8. PubMed.
  2. . Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002 Apr 4;416(6880):542-5. PubMed.