Kim Jeong Mi, Choi Mi Eun, Jeon Eun Jeong, Park Jin-Mi, Kim Sungryeal, Park Jeong Eun, Oh Seung Wook, Choi Jeong-Seok
Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, 27 Inhang-ro, Jung-gu, Incheon 22332, Republic of Korea.
Department of Biomedical Science, Program in Biomedical Science & Engineering, Inha University, 100 Inharo, Michuholgu, Incheon 22212, Republic of Korea.
Regen Ther. 2022 Oct 18;21:453-459. doi: 10.1016/j.reth.2022.09.007. eCollection 2022 Dec.
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 .
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.
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.
Overall, our findings demonstrate that ADMSC-CDVs have potent radioprotective effects on irradiated SG cells.
唾液腺（SG）损伤通常由衰老、辐射和某些药物引起，目前尚无损伤修饰剂。然而，基于间充质干细胞（MSCs）的细胞疗法已被提议作为照射后唾液腺的一种治疗方式。因此，我们将脂肪来源的间充质干细胞（ADMSCs）的细胞衍生囊泡（CDVs）给予照射后的唾液腺细胞，以研究其辐射防护作用。
通过切向流过滤（TFF）纯化和超速离心从ADMSC获得人工CDVs。将培养的人唾液腺上皮细胞暴露于直线加速器产生的2、5或15 Gy的4 MV X射线。通过增殖活性、跨上皮电阻（TEER）和淀粉酶活性测试ADMSC - CDVs对受辐射损伤的唾液腺上皮细胞的影响。
暴露于穿透性辐射会抑制唾液腺上皮细胞的增殖，但降低人下颌下腺上皮细胞（hSMGECs）增殖所需的辐射强度大于其他唾液腺细胞。ADMSC - CDVs恢复了因辐射而降低的唾液腺上皮细胞的增殖能力，并且通过将ADMSC - CDVs给予未受辐射的唾液腺上皮细胞，受辐射的人腮腺上皮细胞（hPGECs）和人舌下腺上皮细胞（hSLGECs）的增殖能力增加。此外，受辐射的hPGECs、hSMGECs和hSLGECs中的淀粉酶活性低于未受辐射的对照组。然而，通过ADMSC - CDV处理，所有细胞的淀粉酶能力均得以恢复。同样，hPGECs、hSMGECs和hSLGECs中的TEER因辐射而降低，并通过给予ADMSC - CDVs得以恢复。
总体而言，我们的研究结果表明ADMSC - CDVs对受辐射的唾液腺细胞具有强大的辐射防护作用。
