Magnetic bioassembly platforms towards the generation of extracellular vesicles from human salivary gland functional organoids for epithelial repair

被引：28

作者：

Chansaenroj, Ajjima ^{[1
]}

Adine, Christabella ^{[2
,3
]}

Charoenlappanit, Sawanya ^{[4
]}

Roytrakul, Sittiruk ^{[4
]}

Sariya, Ladawan ^{[5
]}

Osathanon, Thanaphum ^{[6
]}

Rungarunlert, Sasitorn ^{[7
]}

Urkasemsin, Ganokon ^{[7
]}

Chaisuparat, Risa ^{[1
]}

Yodmuang, Supansa ^{[1
,8
]}

Souza, Glauco R. ^{[9
,10
,11
]}

Ferreira, Joao N. ^{[1
,2
]}

机构：

[1] Chulalongkorn Univ, Fac Dent, Avatar Biotechnol Oral Hlth & Hlth Longev Res Uni, Bangkok 10330, Thailand

[2] Natl Univ Singapore, Fac Dent, Singapore 119077, Singapore

[3] Natl Univ Singapore, Fac Engn, Dept Biomed Engn, Singapore 119077, Singapore

[4] Natl Sci & Technol Dev Agcy, Natl Ctr Genet Engn & Biotechnol, Funct Ingredients & Food Innovat Res Grp, Pathum Thani 12120, Thailand

[5] Mahidol Univ, Fac Vet Sci, Monitoring & Surveillance Ctr Zoonot Dis Wildlife, Bangkok 73170, Nakhon Pathom, Thailand

[6] Chulalongkorn Univ, Fac Dent, Dept Anat, Bangkok 10330, Thailand

[7] Mahidol Univ, Fac Vet Sci, Dept Preclin & Appl Anim Sci, Bangkok 73170, Nakhon Pathom, Thailand

[8] Chulalongkorn Univ, Fac Med, Res Affairs, Bangkok 10330, Thailand

[9] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA

[10] Nano3D Biosci Inc, Houston, TX 77030 USA

[11] Greiner Bioone North Amer Inc, Monroe, NC 28110 USA

来源：

BIOACTIVE MATERIALS | 2022年 / 18卷

基金：

英国医学研究理事会;

关键词：

Salivary gland; Hyposalivation; Human dental pulp stem cells; Magnetic bioassembly; Organoids; Exosome; POLY(ETHYLENE GLYCOL) HYDROGELS; PROGENITOR CELLS; TISSUE; EXPANSION; XEROSTOMIA; MANAGEMENT; MESENCHYME; EXOSOMES; THERAPY; MODEL;

D O I：

10.1016/j.bioactmat.2022.02.007

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页码：151 / 163

页数：13

共 57 条

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