TY  - JOUR
A1  - Koch, Benjamin Florian
A1  - Geßner, Alec
A1  - Farmand, Samira
A1  - Fuhrmann, Dominik Christian
A1  - Geburtig-Chiocchetti, Andreas
A1  - Schubert, Ralf
A1  - Baer, Patrick C.
T1  - Effects of hypoxia on RNA cargo in extracellular vesicles from human adipose-derived stromal/stem cells
T2  - International journal of molecular sciences
N2  - Mesenchymal stromal/stem cells and their derivates are the most promising cell source for cell therapies in regenerative medicine. The application of extracellular vesicles (EVs) as cell-free therapeuticals requires particles with a maximum regenerative capability to enhance tissue and organ regeneration. The cargo of mRNA and microRNA (miR) in EVs after hypoxic preconditioning has not been extensively investigated. Therefore, the aim of our study was the characterization of mRNA and the miR loading of EVs. We further investigated the effects of the isolated EVs on renal tubular epithelial cells in vitro. We found 3131 transcripts to be significantly regulated upon hypoxia. Only 15 of these were downregulated, but 3116 were up-regulated. In addition, we found 190 small RNAs, 169 of these were miRs and 21 were piwi-interacting RNAs (piR). However, only 18 of the small RNAs were significantly altered, seven were miRs and 11 were piRs. Interestingly, all seven miRs were down-regulated after hypoxic pretreatment, whereas all 11 piRs were up-regulated. Gene ontology term enrichment and miR-target enrichment analysis of the mRNAs and miR were also performed in order to study the biological background. Finally, the therapeutic effect of EVs on human renal tubular epithelial cells was shown by the increased expression of three anti-inflammatory molecules after incubation with EVs from hypoxic pretreatment. In summary, our study demonstrates the altered mRNA and miR load in EVs after hypoxic preconditioning, and their anti-inflammatory effect on epithelial cells.
KW  - adipose-derived stromal/stem cells
KW  - mesenchymal stromal/stem cells
KW  - hypoxia
KW  - extracellular vesicles
KW  - translatomics
KW  - RNA
KW  - mRNA
KW  - microRNA
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69246
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-692466
SN  - 1422-0067
N1  - Supplementary Materials: The following are available online at https://www.mdpi.com/article/10.3390/ijms23137384/s1
VL  - 23
IS  - 13, art. 7384
SP  - 1
EP  - 2
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -