Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
StemLab, Venture Incubation Center, Korea University, Seoul 136-701, Korea.
Int J Mol Sci. 2021 Dec 15;22(24):13449. doi: 10.3390/ijms222413449.
Regenerative medicine strategies employing nephron progenitor cells (NPCs) are a viable approach that is worthy of substantial consideration as a promising cell source for kidney diseases. However, the generation of induced nephron progenitor-like cells (iNPCs) from human somatic cells remains a major challenge. Here, we describe a novel method for generating NPCs from human urine-derived cells (UCs) that can undergo long-term expansion in a serum-free condition.
Here, we generated iNPCs from human urine-derived cells by forced expression of the transcription factors OCT4, SOX2, KLF4, c-MYC, and SLUG, followed by exposure to a cocktail of defined small molecules. These iNPCs resembled human embryonic stem cell-derived NPCs in terms of their morphology, biological characteristics, differentiation potential, and global gene expression and underwent a long-term expansion in serum-free conditions.
This study demonstrates that human iNPCs can be readily generated and expanded, which will facilitate their broad applicability in a rapid, efficient, and patient-specific manner, particularly holding the potential as a transplantable cell source for patients with kidney disease.
采用肾祖细胞(NPC)的再生医学策略是一种可行的方法,值得作为肾脏疾病有前途的细胞来源进行大量考虑。然而,从人体体细胞中产生诱导的肾祖细胞样细胞(iNPC)仍然是一个主要挑战。在这里,我们描述了一种从人尿源性细胞(UC)中生成 NPC 的新方法,该方法可以在无血清条件下进行长期扩增。
在这里,我们通过强制表达转录因子 OCT4、SOX2、KLF4、c-MYC 和 SLUG,从人尿源性细胞中生成 iNPC,然后暴露于定义的小分子鸡尾酒中。这些 iNPC 在形态、生物学特性、分化潜能以及全局基因表达方面与人类胚胎干细胞衍生的 NPC 相似,并在无血清条件下进行了长期扩增。
这项研究表明,可以容易地生成和扩增人类 iNPC,这将以快速、高效和个体化的方式促进其广泛应用,特别是作为肾脏疾病患者可移植细胞来源具有潜力。