STEM CELLS IN BONE REGENERATION, A RANDOMIZED CLINICAL TRIAL
Cecilie Gjerde1, Mariano Sanz2, Markus Rojewski3,4, Pierre Layrolle5, Hubert Schrezenmeier3,4, Kamal Mustafa1
1Institute of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway.
2Department of Dental Clinical Specialities (DECO), Faculty of Odontology, University Complutense of Madrid, Spain
3Institute of Transfusion Medicine, Ulm University, Ulm, Germany.
4Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, Red Cross Blood Service
Baden-Württemberg—Hessen and Institute for Transfusion Medicine, University Hospital Ulm, Ulm, Germany.
5INSERM, UMR 1238, PHY-OS, Laboratory of Bone Sarcomas and Remodeling of Calcified Tissues, Faculty of Medicine, University of Nantes, Nantes, France.
Introduction: In a non-controlled recent clinical study, autologous bone marrow derived stem cells combined with biomaterial induced new bone formation. This has been reported as promising new approach for reconstruction of atrophied posterior alveolar mandibular ridges. We aimed in the present study to demonstrate the efficacy of this therapeutic ATMP approach in a randomized multicenter controlled clinical trial.
Our research group has pioneered the field of bone tissue engineering and demonstrated feasibility, safety, and efficacy of the combination of Biphasic Calcium Phosphate (BCP) granules and autologous bone marrow derived stem cells (MSC) in preclinical studies and early phase human clinical trial (n= 11 patients). Successful regeneration of the alveolar bone in the pilot trial was evident in radiographic and histological findings . The findings were supported by the ability of the newly formed tissue to accommodate a dental implant and withstand the forces of mastication on daily bases. Therefore, the present work is aimed to perform phase II multicenter randomized controlled clinical trial for regeneration of mandibular bones of patients prior to dental implants using autologous MSC.
Methodology: Patients with a need for bone reconstruction of residual edentulous ridges in both the mandible and maxilla due to bone defects with a vertical loss of alveolar bone volume and/or knife edge ridges (≤ than 4,5 mm) unable to provide adequate primary stabilization for dental implants were included in the clinical study. Autologous bone marrow MSC were expanded, loaded on BCP (MBCP+™; Biomatlante, France) and used to augment the alveolar ridges. After five months bone biopsies were harvested at the implant position site and implants were installed in the regenerated bone. The implants were loaded after 8 -12 weeks. Safety, efficacy, quality of life and success/survival were assessed. Five clinical centers, 4 different countries participated. Bone grafts harvested from the ramus of the mandibles were used as control in the study.
Results: 41 patients have so far been screened and enrolled in the study. 21 patients have been treated in the test group, 9 in the control group, 6 are waiting for treatment, and 5 withdraw before treatment.
Conclusions: The results this far indicates that the use of bone marrow derived stem cells in the applied protocol for augmentation of the atrophied mandibular ridge have results comparable to the gold standard; autologous bone transplantation with predictable longtime results.
References: Gjerde C et al. Stem Cell Res Ther. 2018 Aug 9;9(1):213