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The loss of healthy cells, though injury or over time, characterises a range of difficult to treat conditions. Stem cells provide a route through which these cells can be replenished, and their transplantation from a range of tissue sources – both autologous and allogeneic – has been identified as a potential therapeutic treatment. However, whilst expectation for their utility in tissue and organ regeneration is high, numerous obstacles to their application remain. This Collection invites research articles investigating stem cell therapy and additionally welcomes submissions focused on overcoming the challenges facing successful stem cell identification, expansion, delivery and engraftment.