Tissue engineering (TE) is promising for the regeneration of failed organs. However, immune rejection, shortage of seed cells, and unintegrated blood vessels restrict the development and clinical application of TE. The last factor is the most challenging and intractable. Harnessing the mature blood vessel network in existing dispensable organs could be a powerful approach to effectively overcome the obstacles. After being remodeled to harbor an immunosuppressive and proregenerative niche, these potential target organs can be transformed into other organs with specific physiological functions, compensating the latter's failed native functions. Organ transformation, such as a hepatized spleen, represents an effective and encouraging TE strategy. In this review, we discuss the current development and obstacles of TE and its feasibility and superiority in organ transformation. After being remodeled to harbor an immunosuppressive and proregenerative niche, these potential target organs can be transformed into other organs with specific physiological functions, compensating for the latter's failed native functions. Organ transformation, such as a hepatized spleen, represents an effective and encouraging tissue engineering strategy. Key points Lack of a mature blood vessel network is the main obstacle to the regeneration of large functional organs. Organ transformation is a powerful and promising regenerative medicine strategy with more flexibility and efficiency than traditional tissue engineering. The spleen is a suitable organ for transformation due to its superior physiological structure, including existent mature blood vessel networks and dispensable function.