Reprogramming of HUVECs into Induced Pluripotent Stem Cells (HiPSCs), Generation and Characterization of HiPSC-Derived Neurons and Astrocytes

被引：13

作者：

Haile, Yohannes ^{[1
]}

Nakhaei-Nejad, Maryam ^{[1
]}

Boakye, Paul A. ^{[2
,3
]}

Baker, Glen ^{[3
,4
]}

Smith, Peter A. ^{[2
,3
]}

Murray, Allan G. ^{[1
]}

Giuliani, Fabrizio ^{[1
,3
]}

Jahroudi, Nadia ^{[1
]}

机构：

[1] Univ Alberta, Dept Med, Edmonton, AB, Canada

[2] Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada

[3] Univ Alberta, Neurosci & Mental Hlth Inst, Edmonton, AB, Canada

[4] Univ Alberta, Dept Psychiat, Neurochem Res Unit, Edmonton, AB, Canada

来源：

PLOS ONE | 2015年 / 10卷 / 03期

基金：

加拿大健康研究院;

关键词：

MICROTUBULE-ASSOCIATED PROTEIN-2; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; CLINICAL-TRIAL; AMINO-ACIDS; ACTIVIN-A; IPS CELLS; EXPRESSION; DIFFERENTIATION; INDUCTION;

D O I：

10.1371/journal.pone.0119617

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neurodegenerative diseases are characterized by chronic and progressive structural or functional loss of neurons. Limitations related to the animal models of these human diseases have impeded the development of effective drugs. This emphasizes the need to establish disease models using human-derived cells. The discovery of induced pluripotent stem cell (iPSC) technology has provided novel opportunities in disease modeling, drug development, screening, and the potential for "patient-matched" cellular therapies in neurodegenerative diseases. In this study, with the objective of establishing reliable tools to study neurodegenerative diseases, we reprogrammed human umbilical vein endothelial cells (HUVECs) into iPSCs (HiPSCs). Using a novel and direct approach, HiPSCs were differentiated into cells of central nervous system (CNS) lineage, including neuronal, astrocyte and glial cells, with high efficiency. HiPSCs expressed embryonic genes such as nanog, sox2 and Oct-3/4, and formed embryoid bodies that expressed markers of the 3 germ layers. Expression of endothelial-specific genes was not detected in HiPSCs at RNA or protein levels. HiPSC-derived neurons possess similar morphology but significantly longer neurites compared to primary human fetal neurons. These stem cell-derived neurons are susceptible to inflammatory cell-mediated neuronal injury. HiPSC-derived neurons express various amino acids that are important for normal function in the CNS. They have functional receptors for a variety of neurotransmitters such as glutamate and acetylcholine. HiPSC-derived astrocytes respond to ATP and acetylcholine by elevating cytosolic Ca2+ concentrations. In summary, this study presents a novel technique to generate differentiated and functional HiPSC-derived neurons and astrocytes. These cells are appropriate tools for studying the development of the nervous system, the pathophysiology of various neurodegenerative diseases and the development of potential drugs for their treatments.

引用

页数：25

共 76 条

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