Summary: Generation of new kidneys can be useful in various research fields, including organ transplantation. However, generating renal stroma, an important component tissue for structural support, endocrine function, and kidney development, remains difficult. Organ generation using an animal developmental niche can provide an appropriate in vivo environment for renal stroma differentiation. Here, we generate rat renal stroma with endocrine capacity by removing mouse stromal progenitor cells (SPCs) from the host developmental niche and transplanting rat SPCs. Furthermore, we develop a method to replace both nephron progenitor cells (NPCs) and SPCs, called the interspecies dual replacement of the progenitor (i-DROP) system, and successfully generate functional chimeric kidneys containing rat nephrons and stroma. This method can generate renal tissue from progenitors and reduce xenotransplant rejection. Moreover, it is a safe method, as donor cells do not stray into nontarget organs, thus accelerating research on stem cells, chimeras, and xenotransplantation.
