학술논문
Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia:A Safety Study (MESRIX-II)
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Electronic Resource
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Lynggaard , C D , Grønhøj , C , Christensen , R , Fischer-Nielsen , A , Melchiors , J , Specht , L , Andersen , E , Mortensen , J , Oturai , P , Barfod , G H , Haastrup , E K , Møller-Hansen , M , Haack-Sørensen , M , Ekblond , A , Kastrup , J , Jensen , S B & von Buchwald , C 2022 , ' Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia : A Safety Study (MESRIX-II) ' , Stem Cells Translational Medicine , vol. 11 , no. 5 , pp. 478-489 .
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Abstract
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.