Abstract
After radioiodine (RI) therapy, patients with thyroid cancer frequently suffer from painful salivary gland (SG) swelling, xerostomia, taste alterations, and oral infections. This study was aimed to determine whether adipose-derived mesenchymal stem cells (AdMSCs) might restore RI-induced SG dysfunction in a murine model. Forty -five mice were divided into three groups; a PBS sham group, a RI+ PBS sham group (0.01 mCi/g mouse, orally), and an RI+AdMSCs (1 × 105 cells/150 uL, intraglandular injection on experimental day 28) treated group. At 16 weeks after RI treatment, body weights, SG weight, salivary flow rates (SFRs), and salivary lag times were measured. Morphologic and histologic examinations and immunohistochemistry (IHC) were performed and the activities of amylase and EGF in saliva were also measured. Changes in salivary 99mTc pertechnetate excretion were followed by SPECT and TUNEL assays were performed. The body and SG weights were similar in the AdMSCs and sham groups. Hematoxylin and eosin staining revealed the AdMSCs group had more mucin-containing acini than the RI group. Furthermore, AdMSCs treatment resulted in tissue remodeling and elevated expressions of epithelial (AQP5) and endothelial (CD31) markers, and increased SFRs. The activities of amylase and EGF were higher in the AdMSCs group than in the RI treated group. 99mTc pertechnetate excretions were similar in the AdMSCs and sham group. Also, TUNEL positive apoptotic cell numbers were less in the AdMSCs group than in the RI group. Local delivery of AdMSCs might regenerate SG damage induced by RI.
Highlights
After radioiodine (RI) therapy, patients with thyroid cancer frequently suffer from painful salivary gland (SG) swelling, xerostomia, taste alterations, and oral infections
At 16 weeks after RI treatment, mice in the RI + PBS sham group were lighter than the PBS sham group (P < 0.01, Fig. 1A), whereas body weight was preserved in the RI+adipose-derived mesenchymal stem cells (AdMSCs) group
Mean SG weight was lower in the RI + PBS sham group than in the PBS sham group (p < 0.05, Fig. 1B), but mean SG weights were similar in the RI+AdMSCs and PBS sham groups
Summary
After radioiodine (RI) therapy, patients with thyroid cancer frequently suffer from painful salivary gland (SG) swelling, xerostomia, taste alterations, and oral infections. The densities of MSCs in adipose tissues are higher than those in bone marrow[15], and adipose-derived mesenchymal stem cells (AdMSCs) maintain the characters of multipotent progenitor cells and capacities for tissue regeneration, trophic effects, and innate immune response[16,17]. For these reasons, AdMSCs have been widely used for tissue restoration and tissue regeneration engineering. No study has yet addressed the regenerative effects or mechanism of AdMSCs on RI-induced SG dysfunction, the extent of SG damage resulting from RI treatment differs from that caused by external beam radiation[21]
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