Osama Muhammad Maria1, Mostafa Shalaby2, Alasdair Syme3, Nicoletta Eliopoulos4, Thierry Muanza5. 1. Experimental Medicine Department, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Surgery Department, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Radiation Oncology Department, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 2. Dawson College, Montreal, Quebec, Canada. 3. Radiation Oncology Department, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Medical Physics Unit, Montreal, Quebec, Canada; Oncology Department, McGill University, Montreal, Quebec, Canada. 4. Surgery Department, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada. 5. Experimental Medicine Department, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Radiation Oncology Department, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Oncology Department, McGill University, Montreal, Quebec, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada. Electronic address: tmuanza@yahoo.com.
Abstract
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been used to minimize and repair radiation-induced normal tissue injury in the intestine, salivary gland, liver, skin, lungs and cardiac muscle. This study investigated the ability of adipose tissue-derived MSCs (aMSCs) to minimize and/or repair single dose radiation-induced oral mucositis (RIOM). METHODS: Syngenic phenotypically and functionally characterized BALB/c mouse aMSCs were implanted intraperitoneally in a RIOM mouse model with different dosing protocols. Response was quantified macroscopically, microscopically and by using different histological and clinically relevant parameters. RESULTS: Irradiation at 18 Gy generated a self-resolved single-dose RIOM BALB/c mouse model with 5.6 ± 0.3 days mean duration (95% confidence interval (CI) 4.233-7.1 days) and 100% survival rate. Intraperitoneal implantation of 5 doses of 2.5 million freshly cultured syngenic aMSCs significantly and reproducibly reduced RIOM ulcer duration to 1.6 ± 0.3 days (95% CI 0.0233-3.1 days, a 72% reduction in RIOM ulcer duration), ulcer size and ulcer floor epithelial height. The therapeutic benefits were significantly dependent on dose size and frequency, number of doses, and therapy onset time. aMSCs therapy significantly minimized the RIOM-related weight loss, accelerated the weight gain and improved irradiated animals' hydration and nutritional status. aMSCs therapy did not potentiate head and neck cancer in vitro. CONCLUSIONS: Syngenic freshly cultured aMSCs significantly minimized and repaired radiation-induced oral mucositis with a 72% reduction in ulcer duration. aMSCs dose size and frequency, number of doses and therapy onset time are the main keys for optimized therapeutic outcome. aMSCs therapy did not stimulate Head and Neck cancer cell growth in-vitro.
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been used to minimize and repair radiation-induced normal tissue injury in the intestine, salivary gland, liver, skin, lungs and cardiac muscle. This study investigated the ability of adipose tissue-derived MSCs (aMSCs) to minimize and/or repair single dose radiation-induced oral mucositis (RIOM). METHODS: Syngenic phenotypically and functionally characterized BALB/c mouse aMSCs were implanted intraperitoneally in a RIOM mouse model with different dosing protocols. Response was quantified macroscopically, microscopically and by using different histological and clinically relevant parameters. RESULTS: Irradiation at 18 Gy generated a self-resolved single-dose RIOM BALB/c mouse model with 5.6 ± 0.3 days mean duration (95% confidence interval (CI) 4.233-7.1 days) and 100% survival rate. Intraperitoneal implantation of 5 doses of 2.5 million freshly cultured syngenic aMSCs significantly and reproducibly reduced RIOM ulcer duration to 1.6 ± 0.3 days (95% CI 0.0233-3.1 days, a 72% reduction in RIOM ulcer duration), ulcer size and ulcer floor epithelial height. The therapeutic benefits were significantly dependent on dose size and frequency, number of doses, and therapy onset time. aMSCs therapy significantly minimized the RIOM-related weight loss, accelerated the weight gain and improved irradiated animals' hydration and nutritional status. aMSCs therapy did not potentiate head and neck cancer in vitro. CONCLUSIONS: Syngenic freshly cultured aMSCs significantly minimized and repaired radiation-induced oral mucositis with a 72% reduction in ulcer duration. aMSCs dose size and frequency, number of doses and therapy onset time are the main keys for optimized therapeutic outcome. aMSCs therapy did not stimulate Head and Neck cancer cell growth in-vitro.
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