... an undiscovered endogenous repair mechanism?
During the controversy (which is still ongoing) as to whether bone marrow derived stem cells were actually becoming hepatocytes or they were merely fusing with existing hepatocytes, (resulting in a cell with a double set of nuclei) one novel therapeutic opportunity was overlooked. As Camargo et al (1) recently showed, hematopoietic stem cells will spontaneously fuse with hepatocytes.
This begs the question: is this an endogenous repair mechanism? From the perspective of the study cited there is functional benefit to the fused hepatocyte, and dormant hepato-specific genes from the stem cell become activated in the new fused cell. The implication is that the clean DNA of the stem cell is able to contribute and complement the transcription pool of the older DNA of the hepatocyte.
Does this mean that stem cells can provide temporary rescue for tired, senescent cells? One would think so. Is this an endogenous repair mechanism? In the non pathological scenario we only see cells with multiple nuclei in muscle cells and giant cells. So if it is, it must be extremely rare. An older study suggested that cells with multiple nuclei tend to apoptose sooner (2). However, the apoptosis could have been associated with polyploidy rather than polykaryosis. So is this an aberration or a therapeutic opportunity? Perhaps both. Evidently this is an entirely new aspect of stem cell therapeutics with very little investigative history. It does point the way for a possible rejuvenative therapeutic opportunity for cells that have, as a result of DNA damage, switched on senescent mode genes.
1. J. Clin. Invest. 113:1266–1270 (2004)
2. Cell Prolif. 1999 Dec;32(6):337-49
