低免疫性人类多能干细胞作为肝脏再生医学的强大工具
Piera Trionfini1, Elena Romano1, Marco Varinelli1
1Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
International journal of molecular sciences
|July 29, 2023
概括
这项研究通过使用CRISPR/Cas9.9删除HLA基因,制造出低免疫性诱导的多能干细胞 (iPSC). 这些修改后的iPSC显示出具有成本效益的,现成的细胞疗法,特别是肝脏疾病的潜力.
科学领域:
- 干细胞生物学 干细胞生物学
- 免疫学 免疫学 免疫学
- 基因编辑 基因编辑
背景情况:
- 诱导多能干细胞 (iPSCs) 提供再生医学潜力,但面临着成本,可扩展性和对全基因使用的免疫排斥等挑战.
- 目前克服异构iPSCs免疫排斥的策略包括基因组编辑,以减少人类白细胞抗原 (HLA) 表达.
研究的目的:
- 通过消除HLA类I和II表达来开发一个低免疫性iPSC线,用于潜在的全原细胞疗法.
- 评估工程 iPSC 线的多能性,分化能力和特定肝细胞分化潜力.
主要方法:
- 利用CRISPR/Cas9基因编辑系统删除β-2-微型球蛋白 (B2M) 和II类主要基因相容性复合体交互激活器 (CIITA) 基因.
- 对多能性标记物,型稳定性和分化潜力进入三个胚胎胚胎层的结果iPSC线的特征.
- 评估了对各种肝细胞类型的特定分化能力.
主要成果:
- 成功生成了具有正常型和维持多能性标志物的低免疫性iPSC线.
- 经过工程设计的iPSC保留了将其分化为所有三个胚胎胚胎层的能力.
- 证明了低免疫性iPSCs的特异分化为内皮状,肝细胞状和肝星状细胞.
结论:
- 通过CRISPR/Cas9介导的B2M和CIITA删除生成的免疫性低免疫性iPSCs为克服细胞治疗中的免疫障碍提供了一个有希望的策略.
- 这些工程化iPSC为再生医学提供了潜在的成本效益高,现成的解决方案,特别是用于治疗肝脏疾病.
相关概念视频
01:22iPS Cell Differentiation
2.7K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.7K
01:06Induced Pluripotent Stem Cells
4.2K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.2K