Magnetic bioassembly platforms towards the generation of extracellular vesicles from human salivary gland functional organoids for epithelial repair
Issued Date
2022-12-01
Resource Type
ISSN
2452199X
Scopus ID
2-s2.0-85124675545
Journal Title
Bioactive Materials
Volume
18
Start Page
151
End Page
163
Rights Holder(s)
SCOPUS
Bibliographic Citation
Bioactive Materials Vol.18 (2022) , 151-163
Suggested Citation
Chansaenroj A., Adine C., Charoenlappanit S., Roytrakul S., Sariya L., Osathanon T., Rungarunlert S., Urkasemsin G., Chaisuparat R., Yodmuang S., Souza G.R., Ferreira J.N. Magnetic bioassembly platforms towards the generation of extracellular vesicles from human salivary gland functional organoids for epithelial repair. Bioactive Materials Vol.18 (2022) , 151-163. 163. doi:10.1016/j.bioactmat.2022.02.007 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/84578
Title
Magnetic bioassembly platforms towards the generation of extracellular vesicles from human salivary gland functional organoids for epithelial repair
Author's Affiliation
Faculty of Dentistry
Chulalongkorn University
University of Texas Health Science Center at Houston
National University of Singapore
Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
Faculty of Medicine, Chulalongkorn University
Greiner Bio-One North America, Inc.
Nano3D Biosciences
Chulalongkorn University
University of Texas Health Science Center at Houston
National University of Singapore
Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
Faculty of Medicine, Chulalongkorn University
Greiner Bio-One North America, Inc.
Nano3D Biosciences
Other Contributor(s)
Abstract
Salivary glands (SG) are exocrine organs with secretory units commonly injured by radiotherapy. Bio-engineered organoids and extracellular vesicles (EV) are currently under investigation as potential strategies for SG repair. Herein, three-dimensional (3D) cultures of SG functional organoids (SGo) and human dental pulp stem cells (hDPSC) were generated by magnetic 3D bioassembly (M3DB) platforms. Fibroblast growth factor 10 (FGF10) was used to enrich the SGo in secretory epithelial units. After 11 culture days via M3DB, SGo displayed SG-specific acinar epithelial units with functional properties upon neurostimulation. To consistently develop 3D hDPSC in vitro, 3 culture days were sufficient to maintain hDPSC undifferentiated genotype and phenotype for EV generation. EV isolation was performed via sequential centrifugation of the conditioned media of hDPSC and SGo cultures. EV were characterized by nanoparticle tracking analysis, electron microscopy and immunoblotting. EV were in the exosome range for hDPSC (diameter: 88.03 ± 15.60 nm) and for SGo (123.15 ± 63.06 nm). Upon ex vivo administration, exosomes derived from SGo significantly stimulated epithelial growth (up to 60%), mitosis, epithelial progenitors and neuronal growth in injured SG; however, such biological effects were less distinctive with the ones derived from hDPSC. Next, these exosome biological effects were investigated by proteomic arrays. Mass spectrometry profiling of SGo exosomes predicted that cellular growth, development and signaling was due to known and undocumented molecular targets downstream of FGF10. Semaphorins were identified as one of the novel targets requiring further investigations. Thus, M3DB platforms can generate exosomes with potential to ameliorate SG epithelial damage.