Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage

Jeong Mi Kim; Mi Eun Choi; Eun Jeong Jeon; Jin-Mi Park; Sungryeal Kim; Jeong Eun Park; Seung Wook Oh; Jeong-Seok Choi

doi:10.1016/j.reth.2022.09.007

Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage

Regen Ther. 2022 Oct 18:21:453-459. doi: 10.1016/j.reth.2022.09.007. eCollection 2022 Dec.

Authors

Jeong Mi Kim^{1

2}, Mi Eun Choi¹, Eun Jeong Jeon^{1

2}, Jin-Mi Park¹, Sungryeal Kim¹, Jeong Eun Park³, Seung Wook Oh³, Jeong-Seok Choi^{1

2

4}

Affiliations

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, 27 Inhang-ro, Jung-gu, Incheon 22332, Republic of Korea.
² Department of Biomedical Science, Program in Biomedical Science & Engineering, Inha University, 100 Inharo, Michuholgu, Incheon 22212, Republic of Korea.
³ Biodrone Research Institute, MDimune Inc., Seoul 04790, Republic of Korea.
⁴ Research Center for Controlling Intercellular Communication (RCIC), College of Medicine, Inha University, 100 Inharo, Michuhol-gu, Incheon 22212, Republic of Korea.

Abstract

Introduction: Salivary gland (SG) damage is commonly caused by aging, irradiation, and some medications, and currently, no damage modifying agent is available. However, cell therapy based on mesenchymal stem cells (MSCs) has been proposed as a therapeutic modality for irradiated SGs. Therefore, we administered cell-derived vesicles (CDVs) of adipose-derived mesenchymal stem cells (ADMSCs) to irradiated SG cells to investigate their radioprotective effects in vitro.

Methods: The artificial CDVs were obtained from ADMSC by tangential flow filtration (TFF) purification and ultracentrifugation. Cultured human SG epithelial cells were exposed to 2, 5 or 15 Gy of 4 MV X-rays produced by a linear accelerator. The effects of ADMSC-CDVs on SG epithelial cells damaged by irradiation were tested by proliferation activity, transepithelial electrical resistance (TEER), and amylase activity.

Results: Exposure to penetrating radiation inhibited the proliferation of SG epithelial cells, but the radiation intensity required to reduce the proliferation of human submandibular gland epithelial cells (hSMGECs) was greater than required for other SG cells. ADMSC-CDVs restored the proliferative ability of SG epithelial cells reduced by irradiation, and the proliferation capacities of irradiated human parotid gland epithelial cells (hPGECs) and human sublingual gland epithelial cells (hSLGECs) were increased by administering ADMSC-CDVs to non-irradiated SG epithelial cells. Furthermore, amylase activity in irradiated hPGECs, hSMGECs, and hSLGECs was lower than in non-irradiated controls. However, amylase ability was restored in all by ADMSC-CDV treatment. Also, TEER was diminished by irradiation in hPGECs, hSMGECs, and hSLGECs and restored by ADMSC-CDV administration.

Conclusion: Overall, our findings demonstrate that ADMSC-CDVs have potent radioprotective effects on irradiated SG cells.

Keywords: ADMSCs, Adipose-derived mesenchymal stem cells; Adipose-derived mesenchymal stem cells (ADMSCs); CDVs, Cell-derived vesicles; Cell-derived vesicles (CDVs); Irradiation; MSCs, Mesenchymal stem cells; SG, Salivary gland; Salivary gland; TEER, Transepithelial electrical resistance; TFF, Tangential flow filtration; hPGECs, human parotid gland epithelial cells; hPL, human platelet lysate; hSLGECs, human sublingual gland epithelial cells; hSMGECs, human submandibular gland epithelial cells.