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Sci Rep. 2017 Aug 31;7(1):10166. doi: 10.1038/s41598-017-10394-y.

Small molecule-based lineage switch of human adipose-derived stem cells into neural stem cells and functional GABAergic neurons.

Author information

1
Lab. of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute and School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea.
2
Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
3
Division of Functional Food Research, Korea Food Research Institute (KFRI), Seongnam, 13539, Republic of Korea.
4
Department of Surgery, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, 06236, Republic of Korea.
5
Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
6
Division of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of Medicine, Seoul, 110799, Republic of Korea.
7
Department of Psychiatry, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
8
Department of Psychiatry, Asan Medical Center, Seoul, 05505, Republic of Korea.
9
Department of Brain & Cognitive Sciences, College of Natural Science, Seoul National University, Seoul, 08826, Republic of Korea.
10
Lab. of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute and School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea. mschang@snu.ac.kr.
11
Neuroscience Research Institute, Seoul National University, Seoul, 03080, Republic of Korea. mschang@snu.ac.kr.

Abstract

Cellular reprogramming using small molecules (SMs) without genetic modification provides a promising strategy for generating target cells for cell-based therapy. Human adipose-derived stem cells (hADSCs) are a desirable cell source for clinical application due to their self-renewal capacity, easy obtainability and the lack of safety concerns, such as tumor formation. However, methods to convert hADSCs into neural cells, such as neural stem cells (NSCs), are inefficient, and few if any studies have achieved efficient reprogramming of hADSCs into functional neurons. Here, we developed highly efficient induction protocols to generate NSC-like cells (iNSCs), neuron-like cells (iNs) and GABAergic neuron-like cells (iGNs) from hADSCs via SM-mediated inhibition of SMAD signaling without genetic manipulation. All induced cells adopted morphological, molecular and functional features of their bona fide counterparts. Electrophysiological data demonstrated that iNs and iGNs exhibited electrophysiological properties of neurons and formed neural networks in vitro. Microarray analysis further confirmed that iNSCs and iGNs underwent lineage switch toward a neural fate. Together, these studies provide rapid, reproducible and robust protocols for efficient generation of functional iNSCs, iNs and iGNs from hADSCs, which have utility for modeling disease pathophysiology and providing cell-therapy sources of neurological disorders.

PMID:
28860504
PMCID:
PMC5579051
DOI:
10.1038/s41598-017-10394-y
[Indexed for MEDLINE]
Free PMC Article

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