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Three-dimensional brain-like microenvironments facilitate the direct reprogramming of fibroblasts into therapeutic neurons

 Yoonhee Jin  ;  Jung Seung Lee  ;  Jin Kim  ;  Sungjin Min  ;  Soohyun Wi  ;  Ji Hea Yu  ;  Gyeong-Eon Chang  ;  Ann-Na Cho  ;  Yeeun Choi  ;  Da-Hee Ahn  ;  Sung-Rae Cho  ;  Eunji Cheong  ;  Yun-Gon Kim  ;  Hyong-Pyo Kim  ;  Yonghwan Kim  ;  Dong Seok Kim  ;  Hyun Woo Kim  ;  Zhejiu Quan  ;  Hoon-Chul Kang  ;  Seung-Woo Cho 
 Nature Biomedical Engineering, Vol.2 : 522-539, 2018 
Journal Title
 Nature Biomedical Engineering 
Issue Date
Biophysical cues can improve the direct reprogramming of fibroblasts into neurons that can be used for therapeutic purposes. However, the effects of a three-dimensional (3D) environment on direct neuronal reprogramming remain unexplored. Here, we show that brain extracellular matrix (BEM) decellularized from human brain tissue facilitates the plasmid-transfection-based direct conversion of primary mouse embryonic fibroblasts into induced neuronal (iN) cells. We first show that two-dimensional (2D) surfaces modified with BEM significantly increase the generation efficiency of iN cells and enhance neuronal transdifferentiation and maturation. Moreover, in an animal model of ischaemic stroke, iN cells generated on the BEM substrates and transplanted into the brain led to significant improvements in locomotive behaviours. We also show that compared with the 2D BEM substrates, 3D BEM hydrogels recapitulating brain-like microenvironments further promote neuronal conversion and potentiate the functional recovery of the animals. Our findings suggest that 3D microenvironments can boost nonviral direct reprogramming for the generation of therapeutic neuronal cells.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
Yonsei Authors
강훈철(Kang, Hoon Chul) ORCID logo https://orcid.org/0000-0002-3659-8847
김동석(Kim, Dong Seok)
김형표(Kim, Hyoung Pyo) ORCID logo https://orcid.org/0000-0003-1441-8822
조성래(Cho, Sung-Rae) ORCID logo https://orcid.org/0000-0003-1429-2684
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