Boss Stem Cells (or simply Boss Cells) are permanent items that increase the difficulty of the game when active. The first one is acquired by beating the Hand of the King, the QueenTQatS, or Dracula - Final FormRtC with no Boss Stem Cells active, the second by beating either with one active, and so on. However, the fifth Boss Stem Cell is obtained by beating the GiantRotG with four active. The use of Aspects prevents the acquirement of the next Boss Stem Cell.
Boss Stem Cells can be injected and removed at the start of the game in the Tube, as long as one hasn't left the starting area. Each one makes the game significantly harder by increasing enemy tier, density, variety, and limiting healing options. On the other hand, higher difficulty levels also increase cells dropped from enemies and the level of the Legendary Forge, and allow access to new blueprints and bonus doors scattered through the levels, as well as some that are dropped by enemies exclusive to high BSCs. The bonus doors show the number of Boss Stem Cells required to enter and will shine blue if enough are currently active.
When Boss Stem Cells, then named Boss Runes, were added in the v0.5.3 patch of the Foundry Update, they could all be obtained on 0 BSC difficulty and each was dropped by a different boss.