The Lymph Node as a New Site for Kidney Organogenesis

Abstract

The shortage of organs for kidney transplantation has created the need to develop new strategies to restore renal structure and function. Given our recent finding that the lymph node (LN) can serve as an in vivo factory to generate or sustain complex structures like liver, pancreas, and thymus, we investigated whether it could also support kidney organogenesis from mouse renal embryonic tissue (metanephroi). Here we provide the first evidence that metanephroi acquired a mature phenotype upon injection into LN, and host cells likely contributed to this process. Urine-like fluid-containing cysts were observed in several grafts 12 weeks post-transplantation, indicating metanephroi transplants' ability to excrete products filtered from the blood. Importantly, the kidney graft adapted to a loss of host renal mass, speeding its development. Thus, the LN might provide a unique tool for studying the mechanisms of renal maturation, cell proliferation, and fluid secretion during cyst development. Moreover, we provide evidence that inside the LN, short-term cultured embryonic kidney cells stimulated with the Wnt agonist R-Spondin 2 gave rise to a monomorphic neuron-like cell population expressing the neuronal 200-kDa neurofilament heavy marker. This finding indicates that the LN might be used to validate the differentiation potential of candidate stem cells in regenerative nephrology. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:295-307

Toward Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis

“…Our studies indicate that the lymph node can serve as an in vivo factory to generate complex organ structures, including liver, pancreas, thymus, and kidney (60–64). This in vivo bioreactor might offer unprecedented opportunities to study stem cell maturation and function, as well as provide a unique organogenesis site for therapeutic purposes.…”

Tissue-Engineering Approaches to Restore Kidney Function

“…Oxidative stress and apoptosis were markedly reduced as well. Francipane et al injected mouse embryonic kidneys into lymph nodes and found that they subsequently acquired mature phenotypes due to host cell stimuli [74]. They, too, observed urine-like fluid-containing cysts along with the appearance of filtration functions.…”

Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

“…Our prior studies described the LN as an attractive bioreactor supporting the engraftment and function of adult mouse hepatic, pancreatic, and thymic cells (Komori, Boone, DeWard, Hoppo, & Lagasse, ) as well as the functional maturation of several mouse embryonic tissues, including the kidney (Francipane & Lagasse, , , ).…”