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Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction
Published on: April 24, 2016
Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell
Jeong Mi Kim1,2, Mi Eun Choi1, Eun Jeong Jeon1,2
1Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, 27 Inhang-ro, Jung-gu, Incheon 22332, Republic of Korea.
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.
Insights
Cell-derived vesicles from mesenchymal stem cells show radioprotective effects on salivary gland cells damaged by irradiation. These vesicles restored cell proliferation, amylase activity, and electrical resistance in vitro.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Radiation Oncology
Background:
- Salivary gland damage from radiation, aging, or medications lacks effective treatments.
- Mesenchymal stem cell (MSC) therapy is a potential treatment for irradiated salivary glands.
- Cell-derived vesicles (CDVs) from MSCs offer a cell-free therapeutic approach.
Purpose of the Study:
- To investigate the radioprotective effects of adipose-derived mesenchymal stem cell-derived vesicles (ADMSC-CDVs) on irradiated salivary gland cells in vitro.
- To evaluate the impact of ADMSC-CDVs on salivary gland epithelial cell proliferation, function, and barrier integrity post-irradiation.
Main Methods:
- ADMSC-CDVs were purified using tangential flow filtration and ultracentrifugation.
- Human salivary gland epithelial cells were irradiated with 4 MV X-rays (2, 5, or 15 Gy).
- Effects of ADMSC-CDVs were assessed by measuring cell proliferation, transepithelial electrical resistance (TEER), and amylase activity.
Main Results:
- Irradiation inhibited salivary gland epithelial cell proliferation, with varying sensitivity among cell types.
- ADMSC-CDVs significantly restored proliferation in irradiated cells.
- Treatment with ADMSC-CDVs also restored amylase activity and TEER in irradiated salivary gland cells, indicating improved function and barrier integrity.
Conclusions:
- ADMSC-CDVs demonstrate potent radioprotective effects on irradiated salivary gland cells.
- This study highlights the therapeutic potential of ADMSC-CDVs for mitigating radiation-induced salivary gland damage.
- ADMSC-CDVs represent a promising cell-free therapeutic strategy for salivary gland protection.
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