Perhaps most worrisome of all is the risk of immune rejection and attendant inflammation and cerebritis, which may be coupled to the destruction of grafted cells and consequent transplant failure. Both tissue and cell transplantation trials have generally included transient systemic T cell-targeted immunosuppressive therapy, most typically with calcineurin inhibitors such as cyclosporine or tacrolimus. Nonetheless, the use of these agents for prophylaxis of graft rejection in the CNS has been fundamentally empiric, as optimal protocols for immunosuppressant coverage have yet to be established for intracerebral grafts; neither the degree of systemic immunosuppression required nor the length of time that it should be maintained have been systematically studied, nor has the extent to which these protocols might be varied as a function of either donor cell type or host disease environment. Furthermore, the risks of chronic immunosuppression are not insignificant, and must be considered in any risk-benefit analysis of any cell transplant strategy.
