1. Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia:A Safety Study (MESRIX-II)
- Author
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Charlotte Duch Lynggaard, Christian Grønhøj, Robin Christensen, Anne Fischer-Nielsen, Jacob Melchiors, Lena Specht, Elo Andersen, Jann Mortensen, Peter Oturai, Gry Hoffmann Barfod, Eva Kannik Haastrup, Michael Møller-Hansen, Mandana Haack-Sørensen, Annette Ekblond, Jens Kastrup, Siri Beier Jensen, and Christian von Buchwald
- Subjects
Male ,clinical trials ,mesenchymal stem cells ,SALIVARY ,IMPACT ,Hematopoietic Stem Cell Transplantation ,Mesenchymal Stem Cells ,Cell Biology ,General Medicine ,Xerostomia ,MECHANISMS ,LIFE ,stomatognathic system ,Head and Neck Neoplasms ,stem cells ,Humans ,cancer ,Female ,HEAD ,Radiation Injuries ,xerostomia ,Developmental Biology - 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.
- Published
- 2022