Renal organogenesis in the lymph node microenvironment

Abstract The shortage of organs for kidney transplantation has created an urgent need to find alternative treatment options. Recently, the combination of organoid cell culture technology with methodologies to fabricate three-dimensional scaffolds emerged as a promising approach to improve the function of several organs, including the kidney. An alternative approach is to urge organoids to mature into functional tissues by directly implanting them into a supportive niche in the host. Our unique approach takes advantage of the lymph node as a surrogate niche for functional kidney organogenesis. In the lymph node, primary mouse and human embryonic kidney fragments were nurtured and functionally matured. The lymph node also supported the engraftment and differentiation of organoid cultures derived from both mouse nephron progenitors and human-induced pluripotent stem cells that had been directed toward kidney fates. What makes the lymph node such a supportive site is its vascular-stromal network, which likely conveys specific cues to the developing transplanted tissue whether it be kidney or any other tissue. Further studies will be necessary to demonstrate the therapeutic efficacy of this approach. In this chapter, I will briefly discuss current strategies and challenges for the engineering of a functional kidney, and discuss our strategy exploiting the lymph node microenvironment.