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Growth and differentiation of human induced pluripotent stem cell(hiPSC)-derived kidney organoids using fully synthetic peptide hydrogels

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Bioactive Materials 2023年第3期21卷 142-156页

作者： Niall J.Treacy Shane Clerkin Jessica L.Davis Ciar´an kennedy Aline F.Miller Alberto Saiani jacek k.wychowaniec Dermot F.Brougham John Crean Diabetes Complications Research Centre University College Dublin(UCD)Conway Institute of Biomolecular and Biomedical Research and BelfieldDublin 4Ireland UCD School of Biomolecular and Biomedical Science BelfieldDublin 4Ireland Department of Materials&Manchester Institute of Biotechnology(MIB) School of Natural SciencesFaculty of Science and EngineeringThe University of ManchesterUK UCD School of Chemistry University College DublinBelfieldDublin 4Ireland

Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised ***,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid *** within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and ***,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,***-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct *** compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell ***,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression ***-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid *** work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.

关键词： Human kidney organoids Fully synthetic matrices Self-assembling peptide hydrogels Single-cell RNA sequencing

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