title: Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Osama Muhammad
authors.initials: OM
authors.lastname: Maria
authors.affiliation: Dawson College, Montreal, Quebec, Canada.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Shalaby
authors.affiliation: Radiation Oncology Department, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Medical Physics Unit, Montreal, Quebec, Canada; Oncology Department, McGill University, Montreal, Quebec, Canada.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Syme
authors.affiliation: Surgery Department, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Eliopoulos
authors.affiliation: 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.
authors.forename: Thierry
authors.initials: T
authors.lastname: Muanza
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D008807:Mice, Inbred BALB C; D011833:Radiation Injuries, Experimental / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects*; D013280:Stomatitis / Q000209:etiology / Q000628:therapy*
keywords: adipose tissue; cellular therapy; head and neck cancer; ionizing radiation; mesenchymal stromal cells; normal tissue injury; oral mucositis; radiotherapy