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

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 

作者机构:Diabetes Complications Research CentreUniversity College Dublin(UCD)Conway Institute of Biomolecular and Biomedical Research and BelfieldDublin 4Ireland UCD School of Biomolecular and Biomedical ScienceBelfieldDublin 4Ireland Department of Materials&Manchester Institute of Biotechnology(MIB)School of Natural SciencesFaculty of Science and EngineeringThe University of ManchesterUK UCD School of ChemistryUniversity College DublinBelfieldDublin 4Ireland 

出 版 物:《Bioactive Materials》 (生物活性材料(英文))

年 卷 期:2023年第21卷第3期

页      面:142-156页

核心收录:

学科分类:081702[工学-化学工艺] 08[工学] 0817[工学-化学工程与技术] 

基  金:This publication has emanated from research conducted with the financial support of Science Foundation Ireland(SFI) co-funded under the European Regional Development Fund under Grant Number 13/RC/2073_P2 The authors acknowledge support from Science Foundation Ireland(16/IA/4584) 19/FFP/6833.J.K.W.would also like to acknowledge Royal Society of Chemistry grant(M19-6613) 

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

摘      要: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.

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