AUTHOR=Montagud-Marrahi Enrique , Rodriguez-Gonzalo Adriana , López-Aladid Rubén , Luque Yosu , Rabadán-Ros Ruben , Cuadrado-Payan Elena , Bañón-Maneus Elisenda , Rovira Jordi , Lazo-Rodríguez Marta , Aguilà Oriol , Arana Carolt , García-Busquets Ainhoa , Hierro Natalia , Prudhomme Thomas , Musquera Mireia , Xia Yun , Diekmann Fritz , Campistol Josep M. , Ramírez-Bajo Maria José 

TITLE=Enhanced Kidney Targeting and Distribution of Tubuloids During Normothermic Perfusion

JOURNAL=Transplant International

VOLUME=Volume 38 - 2025

YEAR=2025

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.14747

DOI=10.3389/ti.2025.14747

ISSN=1432-2277

ABSTRACT=Tubuloids have become a promising tool for modeling and regenerating kidney disease, although their ability for integration and regeneration in vivo is not well documented. Here, we established, characterized, and compared human tubuloids using two optimized protocols: one involving prior isolation of tubular cells (Crude tubuloids) and the other involving prior isolation of proximal tubular cells (F4 tubuloids). Next, healthy rat-derived tubuloids were established using this protocol. Finally, we compared two strategies for delivering GFP tubuloids to a kidney host: 1) subcapsular/intracortical injection and 2) tubuloid infusion during normothermic preservation in a rat transplantation model and a discarded human kidney. F4 tubuloids achieved a higher level of differentiation state compared to Crude tubuloids. When analyzing tubuloid delivery to the kidney, normothermic perfusion was found to be more efficient than in vivo injection. Moreover, fully developed tubules were observed in the host parenchyma at 1 week and 1 month after infusion during normothermic perfusion represent a potential strategy to enhance the translatability of kidney regenerative therapies into clinical practice to condition kidney grafts and to treat kidney diseases.