腺体内现货型异体间充质干细胞治疗放射性口干症患者：一项安全性研究（MESRIX-II）

No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)-xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland.

Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59. 5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred.

During 4 months, UWS flow rate increased from 0. 13 mL/minute at baseline to 0. 18 mL/minute with a change of 0. 06 (P = . 0009) mL/minute. SWS flow rate increased from 0. 66 mL/minute at baseline to 0. 75 mL/minute with a change of 0. 09 (P = . 017) mL/minute. XQ summary score decreased by 22. 6 units (P = . 0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26. 7 (P = . 0013), sticky saliva 23. 3 (P = . 0015), and swallowing 10. 0 (P = . 0016).

Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.