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Artificial cells drive neural differentiation.

ABSTRACT: We report the construction of artificial cells that chemically communicate with mammalian cells under physiological conditions. The artificial cells respond to the presence of a small molecule in the environment by synthesizing and releasing a potent protein signal, brain-derived neurotrophic factor. Genetically controlled artificial cells communicate with engineered human embryonic kidney cells and murine neural stem cells. The data suggest that artificial cells are a versatile chassis for the in situ synthesis and on-demand release of chemical signals that elicit desired phenotypic changes of eukaryotic cells, including neuronal differentiation. In the future, artificial cells could be engineered to go beyond the capabilities of typical smart drug delivery vehicles by synthesizing and delivering specific therapeutic molecules tailored to distinct physiological conditions.

SUBMITTER: Toparlak OD

PROVIDER: S-EPMC7500934 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Artificial cells drive neural differentiation.

Toparlak Ö Duhan ÖD Zasso Jacopo J Bridi Simone S Serra Mauro Dalla MD Macchi Paolo P Conti Luciano L Baudet Marie-Laure ML Mansy Sheref S SS

Science advances 20200918 38

We report the construction of artificial cells that chemically communicate with mammalian cells under physiological conditions. The artificial cells respond to the presence of a small molecule in the environment by synthesizing and releasing a potent protein signal, brain-derived neurotrophic factor. Genetically controlled artificial cells communicate with engineered human embryonic kidney cells and murine neural stem cells. The data suggest that artificial cells are a versatile chassis for the ...[more]

PMID: 32948587

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Project description:Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, colony stimulating factor and interleukin 6 of the STAT3 family and Hes family bHLH transcription factor 1 also increased by 2.3, 10, 4.7 and 2.9 fold, respectively. We further examined the effects of these exosomes on rat fetal neural stem cell (rNSC) differentiation using the secreted exosomes from U87 glioma cells or exosomes from U87 cells that were stimulated with interleukin 1β (IL-1β). The rNSCs, extracted from rat brains at embryonic day 14 (E14), underwent a culture protocol that normally leads to predominant (~90%) differentiation to ODCs. However, in the presence of the exosomes from untreated or IL-1β-treated U87 cells, significantly more cells differentiated into astrocytes, especially in the presence of exosomes obtained from the IL-1β-challenged glioma cells. Moreover, glioma-derived exosomes appeared to inhibit rNSC differentiation into ODCs or astrocytes as indicated by a significantly increased population of unlabeled cells. A portion of the resulting astrocytes co-expressed both CD133 and glial fibrillary acidic protein (GFAP) suggesting that exosomes from U87 cells could promote astrocytic differentiation of NSCs with features expected from a transformed cell. Our data clearly demonstrated that exosomes secreted by human glioma cells provide a strong driving force for rat neural stem cells to differentiate into astrocytes, uncovering potential pathways and therapeutic targets that might control this aggressive tumor type.

Dataset Information

Artificial cells drive neural differentiation.

Publications

Artificial cells drive neural differentiation.

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