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

Jin, Yoonhee; Lee, Jung Seung; Kim, Jin; Min, Sungjin; Wi, Soohyun; Yu, Ji Hea; Chang, Gap Soo; Cho, Ann Na; Choi, Yun Young; Ahn, Da Hee; Cho, Sung Rae; Cheong, Eunji; Kim, Yun Gon; Kim, Hyong Pyo; Kim, Yonghwan; Kim, Do Kyung; Kim, Hyun Woo; Quan, Zhejiu; Kang, Hoon Chul; Cho, Seung Woo

doi:10.1038/s41551-018-0260-8

Cited by 94 publications

(86 citation statements)

References 80 publications

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“…Surprisingly, 3D ECM hydrogel simulating brain microenvironment could accelerate the MET process and have a low contractile force which prevents YAP from entering the nucleus. H3K4me3 and H3K27ac occurred in the promoter region of TUJ1, which activated the relevant transcription and promoted reprogramming directly into functional neurons [88], which further illustrated the importance of extracellular microenvironment for reprogramming.…”

Section: Application Of Physical Factors In the Reprogramming Of Fibrmentioning

confidence: 86%

How to reprogram human fibroblasts to neurons

Zhou

et al. 2020

Cell Biosci

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Destruction and death of neurons can lead to neurodegenerative diseases. One possible way to treat neurodegenerative diseases and damage of the nervous system is replacing damaged and dead neurons by cell transplantation. If new neurons can replace the lost neurons, patients may be able to regain the lost functions of memory, motor, and so on. Therefore, acquiring neurons conveniently and efficiently is vital to treat neurological diseases. In recent years, studies on reprogramming human fibroblasts into neurons have emerged one after another, and this paper summarizes all these studies. Scientists find small molecules and transcription factors playing a crucial role in reprogramming and inducing neuron production. At the same time, both the physiological microenvironment in vivo and the physical and chemical factors in vitro play an essential role in the induction of neurons. Therefore, this paper summarized and analyzed these relevant factors. In addition, due to the unique advantages of physical factors in the process of reprogramming human fibroblasts into neurons, such as safe and minimally invasive, it has a more promising application prospect. Therefore, this paper also summarizes some successful physical mechanisms of utilizing fibroblasts to acquire neurons, which will provide new ideas for somatic cell reprogramming.

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Section: Application Of Physical Factors In the Reprogramming Of Fibrmentioning

confidence: 86%

How to reprogram human fibroblasts to neurons

Zhou

et al. 2020

Cell Biosci

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“…The coupling of a microfluidic device with an organoid has recently been termed "organoid-ona-chip", and this represents an innovative approach in biomedical research 105,106 . Moreover, various engineered materials for organoid culture containing a decellularized matrix and a chemically defined matrix are being actively developed 106,107,111 .…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches

2020

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The recent emergence of organoid technology has attracted great attention in gastroenterology because the gastrointestinal (GI) tract can be recapitulated in vitro using organoids, enabling disease modeling and mechanistic studies. However, to more precisely emulate the GI microenvironment in vivo, several neighboring cell types and types of microbiota need to be integrated into GI organoids. This article reviews the recent progress made in elucidating the crosstalk between GI organoids and components of their microenvironment. We outline the effects of stromal cells (such as fibroblasts, neural cells, immune cells, and vascular cells) on the gastric and intestinal epithelia of organoids. Because of the important roles that microbiota play in the physiology and function of the GI tract, we also highlight interactions between organoids and commensal, symbiotic, and pathogenic microorganisms and viruses. GI organoid models that contain niche components will provide new insight into gastroenterological pathophysiology and disease mechanisms.

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“…S9B, n = 4 to 5 for each group) and injected with 50 ul of a mixture (1:1 ratio) of the 4% (w/w) alginate gel and calcium gluconate solution (112 mg/ml) (or media as control). dECM hydrogel from mouse skeletal muscle (MEM) was prepared as previously reported (51) and also served as a control group. The mice were examined by serial scanning of the hindlimb surface blood flow with the laser Doppler perfusion imager (Moor Instruments, Devon, UK) on days 0, 14, 21, and 28 after treatments.…”

Section: Hindlimb Ischemia Surgery and Biomaterials Injectionmentioning

confidence: 99%

Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization

Jia

Jeon

et al. 2020

Sci. Adv.

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Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials. However, recent decades have shown only limited progress in discovering novel extracellular matrix–protein–derived ligands for translational applications. Through motif analysis of evolutionarily conserved RGD-containing regions in laminin (LM) and peptide-functionalized hydrogel microarray screening, we identified a peptide (a1) that showed superior supports for endothelial cell (EC) functions. Mechanistic studies attributed the results to the capacity of a1 engaging both LM- and Fn-binding integrins. RNA sequencing of ECs in a1-functionalized hydrogels showed ~60% similarities with Matrigel in “vasculature development” gene ontology terms. Vasculogenesis assays revealed the capacity of a1-formulated hydrogels to improve EC network formation. Injectable alginates functionalized with a1 and MMPQK (a vascular endothelial growth factor–mimetic peptide with a matrix metalloproteinase–degradable linker) increased blood perfusion and functional recovery over decellularized extracellular matrix and (RGDS + MMPQK)–functionalized hydrogels in an ischemic hindlimb model, illustrating the power of this approach.

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

Cited by 94 publications

References 80 publications

How to reprogram human fibroblasts to neurons

How to reprogram human fibroblasts to neurons

Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches

Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization

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