3D BIOPRINTED CONSTRUCTS TO GENERATE MATURE ORGANOIDS FROM IPSC-DERIVED RENAL PROGENITORS

Speaker

Addario, Gabriele (Maastricht University-MERLN institute)

Description

Chronic kidney disease (CKD) is characterised by the gradual loss of renal function. It affects approximately 10% of the population worldwide, and the only treatment is aimed to slow down the progression of kidney damage. Ultimately, CKD results in end-stage renal disease (ESRD), which can only be treated with dialysis or renal transplant. However, both options are far from ideal and cannot be considered permanent solutions.
Regenerative medicine, particularly the use of organoids, might provide a solution to this problem. Organoids are a relatively easy and scalable model that can be used to study organ development, regeneration, genetic diseases, and perform drug screening. However, the limited ability to accurately replicate adult organs' maturation level, complexity, and functions drastically restrict their application in research and clinical medicine.We implemented differentiation protocols to obtain iPSC-derived metanephric mesenchyme (MM) and ureteric bud (UB) progenitors in sufficient numbers for bioprinting. We used a microfluidic 3D bioprinter capable of extruding core-shell filaments to manufacture renal constructs containing single cell progenitors. After bioprinting, we cultured the construct with an optimised mix of growth factors for two weeks. The 3D bioprinted renal progenitors showed high viability after bioprinting. After one day in culture, the cells self-aggregated into spheroids inside the hydrogel filaments. Within one week, renal vesicles were visible. Tubular structures were observed two weeks post-bioprinting, which stained positive for lotus tetragonolobus lectin (LTL) and e-cadherin. For the first time, we were able to bioprint iPSC-derived renal progenitors that generated renal organoids inside the bioprinted hydrogel constructs.

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