Human Adipose‐Derived Mesenchymal Stem Cells for Osseous Rehabilitation of Induced Osteoradionecrosis: A Rodent Model

Abstract

Objective Human adipose-derived mesenchymal stem cells (ADSCs) were used to rehabilitate bone damaged by osteoradionecrosis (ORN) in an established animal model. Study Design Prospective animal study. Setting Academic department laboratory. Subjects and Methods After institutional review board and Institutional Animal Care and Use Committee approval, 24 athymic nude rats were divided into 5 groups: 4 groups irradiated (20 Gy) by brachytherapy catheter placed at the left hemimandible and 1 mock irradiation control (n = 4). For all groups, ORN was initiated by extraction of the central molar 1 week later. After 28 days, animals (n = 5/group) received injection at the extraction site with saline (SAL), ADSCs, platelet-rich plasma and collagen (PRP/COL), or ADSCs + PRP/COL. Rats were sacrificed 28 days later and their mandibles harvested for histopathology analysis (osteoblasts, osteoclasts, and fibrosis) and bone volume measurement using 3-dimensional micro-computed tomography. Results All but 1 rat survived the experiment period (23/24). Radiographic and histological analysis revealed 60% bone loss in the SAL group compared with the nonirradiated control. Injection of ADSCs increased jaw region bone volume by up to 36% ( P < .01). All experimental groups (ADSC, PRP/COL, and ADSC + PRP/COL) showed dramatically decreased osteoclast counts ( P < .001) while injection of PRP/COL with or without ADSCs increased osteoblasts. Increased fibrosis was observed after ADSC injection ( P < .05). Conclusion The application of human ADSCs to an induced mandibular osteoradionecrosis model in athymic rats results in increased deposition or preservation of bone, demonstrated both histologically and radiographically. This offers an encouraging possible treatment option for translational research in this difficult disease.

Cell therapy stimulates bone neoformation in calvaria defects in rats subjected to local irradiation

“…ORN can be treated conservatively, using antibiotic and hyperbaric oxygen therapies, but aggressive cases are a clinical challenge that may include substantial surgical resection . Mesenchymal stem cells (MSCs) have been the subject of extensive investigation in the past few decades, including in association with bone regeneration after traumas and neoplasia.…”

“…Jin et al observed in an animal model of ORN that a combined application of rat (r)MSCs and bone morphogenetic protein (BMP)‐2 led to improved bone healing after post‐irradiation dentoalveolar trauma in rats compared to BMP‐2 applied alone. Other positive results showing increased bone deposition or preservation after the application of human adipose tissue‐derived stem cells (ADSCs) to an induced mandibular osteoradionecrosis model in rats have been demonstrated using histological and radiological evaluations . However, there are few reports of investigations demonstrating the effects of cell therapy after irradiation in bones other than femur and mandible.…”

Topical superoxide dismutase in posttreatment fibrosis in patients with head and neck cancer

“…Specific interventions vary widely and depend on the location and degree of fibrosis; these include physiotherapy, massage, progressive occupational therapy, botulinum toxin A injection, microcurrent therapy, mesenchymal stem cell therapy, and surgical treatment. At this time, no existing method of treatment offers complete remission …”

“…At this time, no existing method of treatment offers complete remission. 1,7,8 There has been success in treatment of postradiation fibrosis of patients with breast cancer with topical superoxide dismutase (SOD), indicated by a decrease in pain scores and in the area of fibrosis. 9 SOD is an enzyme found in various tissues throughout the body and has a fundamental role in the elimination of reactive oxidative species and free radicals that cause tissue damage and fibrosis.…”

A Study of the Experience of German Dental Practitioners with Patients on Bisphosphonates or Anticoagulants

“…In case surgery is required during drug intake, specific rules are to be followed. A possible complication is bisphosphonate-related osteonecrosis of the jaw (BRONJ) manifesting as exposed, nonvital bone that does not recover over 8 weeks after current or past bisphosphonate therapy (6,7,8,9,10,11,12) The mains steps included in the Germany clinical protocol for dental sanitation and care in patients receiving or planned to receive bisphosphonate therapy are as follows: (13,14,15)…”