Trophoblast stem cells (TSCs), cells found in the layer of peripheral embryonic stem cells from which the placenta is formed, are thought to exhibit "immune privilege" that aids cell survivability and is potentially beneficial for cell and gene therapies. Further, the survivability of TSCs has been thought to require the presence of ovarian hormones. However, none of these assumptions has ever been verified.
This study, published in the current issue of the journal Cell Transplantation (18:7) - now freely available on-line at http://www.ingentaconnect.com/content/cog/ct - has demonstrated that it is the absence of male hormones, rather than the presence of female hormones, that allows extended transplanted cell survivability.
"Questioning whether a female hormonal environment is one of the physiological requirements for ectopic TSC survival, we surmised that a partially immune-privileged site other than the uterus might also allow TSCs to survive and exert a protective action on other nearby cells, enabling the latter to survive in locations where they normally could not," said Dr. Bert Binas, co-author of the study.
When the research team injected the livers of both male and female mice with TSCs, the cells survived in female animal livers but did not survive in male animal livers.
"This was not unexpected, given the natural uterine environment for TSCs," said Dr. Binas. "However, castration of the male mice abolished the sex hormone difference and the livers of the castrated male mice provided a perfect environment for the TSCs."
The researchers concluded that the presence of male hormones was toxic for the injected TSCs. The injected TSCs survived for three months with little if any proliferation, regardless of their immunological compatibility, but were dependent on a non-male hormonal environment in castrated male mice.
The TSCs were also found to promote survival of another cell type when transplanted together, suggesting that these cells may be able to modify their local environment and enhance the survival of co-transplanted cells. Thus a new "stem cell based trophoblastic approach" to therapeutic cell transplantation may prove to be beneficial.