Clearance of Senescent Liver Cells Following Cell Transplant
Cellular senescence is an important topic in aging: the number of senescent cells increases with age, and they cause harm to surrounding tissues. The research community is on the verge of being able to effectively remove these cells, however, using the tools under development by the cancer research community to target and destroy cancer cells with minimal side effects.
There may also be other ways to deal with senescent cells. The research result below was published earlier this year and makes for an interesting companion piece to a more recently published paper in which researchers showed that a method of growing large numbers of liver cells called hepatocytes via serial transplantation in mice was reversing cellular senescence along the way. Here cancer researchers find that cell transplants into rats have a similar effect, at least for cellular senescence that is artificially induced via introduction of a mild toxin that causes DNA damage and other cellular dysfunction leading to cancer. I would have to see a similar result in old animals with natural levels of cellular senescence before becoming too enthusiastic about this:
Increasing evidence indicates that carcinogenesis is dependent on the tissue context in which it occurs, implying that the latter can be a target for preventive or therapeutic strategies. We tested the possibility that re-normalizing a senescent, neoplastic-prone tissue microenvironment would exert a modulatory effect on the emergence of neoplastic disease.Rats were exposed to a protocol for the induction of hepatocellular carcinoma (HCC). Using an orthotopic and syngeneic system for cell transplantation, one group of animals was then delivered 8 million normal hepatocytes, via the portal circulation. Hepatocytes transplantation resulted in a prominent decrease in the incidence of both pre-neoplastic and neoplastic lesions.
At the end of 1 year 50% of control animals presented with HCC, while no HCC were observed in the transplanted group. Extensive hepatocyte senescence was induced by the carcinogenic protocol in the host liver; however, senescent cells were largely cleared following infusion of normal hepatocytes. Furthermore, levels of Il-6 increased in rats exposed to the carcinogenic protocol, while they returned to near control values in the group receiving hepatocyte transplantation. These results support the concept that strategies aimed at normalizing a neoplastic-prone tissue landscape can modulate progression of neoplastic disease.
Link: http://www.impactaging.com/papers/v6/n1/full/100631.html