Well if Itachi's words hint at anything, Shisui may have unlocked a means without having to kill someone. Taking note of Shisui's character, one can infer that his change in philosophy may have been due to seeing a comrade or beloved die or come close to death. That shift in demeanor may have been an inspiration to Itachi who at the time was going through his own trials. One can also infer that Shisui may have been forced to kill someone who Shisui didn't see as necessary or maybe someone from his own team. Of course this is all conjecture. One can only guess what extraordinary means Shisui achieved in unlocking the Mangekyo Sharingan.
