微流体生物打印作为生产hipscs衍生肾类器官的工具。

IF 8 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Chiara Formica, Gabriele Addario, Sveva Fagiolino, Lorenzo Moroni, Carlos Mota
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引用次数: 0

摘要

慢性肾脏疾病影响全球10%的人口,并经常发展为终末期肾脏疾病,透析或肾移植是唯一的治疗方法,尽管两者都不是永久的解决方案。再生医学,特别是类器官的使用,提供了一个潜在的解决方案。类器官在研究器官发育、疾病和再生方面具有重要价值,适合用于药物筛选。然而,它们复制成人器官成熟度、复杂性和功能的能力有限,限制了它们的应用。此外,人工生产类器官会导致可变性,影响可扩展性和可重复性。生物打印等自动化技术可以通过有控制的方式沉积细胞和生物材料来提高类器官的成熟度和复杂性。在本研究中,我们建立了分化方案,以获得人诱导的多能干细胞衍生的后肾间充质、输尿管芽祖细胞,并将它们结合起来形成类器官。利用一种能够产生核-壳细丝的微流控生物打印机,在海藻酸盐外壳包裹的核中加入明胶,对单细胞祖细胞进行生物打印。这些纤维结构与优化的生长因子混合培养两周。一周内,肾小泡可见,两周后,生物打印后的肾类器官功能正常,并对肾毒性药物阿霉素有反应。总之,开发了一种生物打印方法,可以自动从祖细胞中生成功能性肾类器官,为未来肾脏疾病的治疗提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Microfluidic bioprinting as a tool to produce hiPSCs-derived renal organoids.

Chronic kidney disease affects 10% of the global population and often progresses to end-stage renal disease, where dialysis or renal transplant are the only therapies, though neither is a permanent solution. Regenerative medicine, particularly the use of organoids, offers a potential solution. Organoids are valuable for studying organ development, diseases, and regeneration, and are suitable for drug screening. However, their limited ability to replicate adult organs' maturation, complexity, and functions restricts their application. Additionally, manual production of organoids causes variability, affecting scalability and reproducibility. Automation techniques like bioprinting could enhance organoid maturation and complexity by depositing cells and biomaterials in a controlled manner. In this study, we established differentiation protocols to obtain human induced pluripotent stem cell-derived metanephric mesenchyme, ureteric bud progenitors, and the combination of these was used to form organoids. A microfluidic bioprinter capable of producing core-shell filaments was used to bioprint single cell progenitors in combination with gelatin in the core wrapped with an alginate shell. These filament constructs were cultured with an optimized mixture of growth factors for two weeks. Within one week, renal vesicles were visible, and after two weeks post-bioprinting the kidney organoids were functional and respond to the nephrotoxic drug doxorubicin. In conclusion, a bioprinted method was developed to generate in an automated way functional renal organoids from progenitors, offering a foundation for future kidney disease treatment.

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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
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