Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studi
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Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studies Anders Kierkegaard Gundestrup 1 & Charlotte Duch Lynggaard 1 & Lone Forner 2 & Terhi J. Heino 3 & Kathrine Kronberg Jakobsen 1 & Anne Fischer-Nielsen 4 & Christian Grønhøj 1 & Christian von Buchwald 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment options carry risks with some patients remaining incurable. Mesenchymal stromal/ stem cell (MSC) therapy has shown promising results supporting osteogenesis and regeneration of radiotherapy-damaged tissues. The aim of this study was to systematically review the literature on the safety and efficacy of MSCs in treating ORN. Methods A systematic search was performed on MEDLINE, Embase, Cochranes Library online databases, and clinicaltrials.gov to identify preclinical and clinical studies examining the effect of MSCs on osseous healing of ORN. The preclinical studies were assessed according to the SYRCLEs guidelines and risk of bias tool. Results Six studies (n = 142) from 5 countries were eligible for analysis. Of these four were preclinical studies and two clinical case studies. Preclinical studies found MSC treatment to be safe, demonstrating bone restorative effects and improved soft tissue regeneration. In the clinical cases, healing of bone and soft tissue was reported with no serious adverse events. Conclusion The evidence from the included studies suggests that MSCs may have beneficial regenerative effects on the healing of ORN. None of the studies reported adverse events with the use of MSCs. More carefully controlled studies with well-identified cells are however needed to demonstrate the efficacy of MSCs in a clinical setting.
Keywords Osteoradionecrosis . Mesenchymal stem cells . Cell therapy . ORN . Systematic review
Introduction Osteoradionecrosis of the mandible (ORN) is a complication of high-dose radiotherapy of the head and neck. The currently accepted definition of the condition is bone devitalization secondary to radiotherapy, where bone becomes exposed through
* Christian von Buchwald [email protected] 1
Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
2
Department of Oral and Maxillofacial Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
3
Institute of Biomedicine, Faculty of Medicine, University of Turku, Turku, Finland
4
Department of Immunology, Cell Therapy Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
the overlying skin or mucosa without healing for three months in the absence of recurrent tumor [1, 2]. ORN often occurs as a consequence of local trauma but may also arise spontaneously, and ranges from small asymptomatic bone exposures to severe necrosis with pathologi
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