Adipose Stem Cells Used to Reconstruct 13 Cases With Cranio-Maxillofacial Hard-Tissue Defects

Abstract

Although isolated reports of hard-tissue reconstruction in the cranio-maxillofacial skeleton exist, multipatient case series are lacking. This study aimed to review the experience with 13 consecutive cases of cranio-maxillofacial hard-tissue defects at four anatomically different sites, namely frontal sinus (3 cases), cranial bone (5 cases), mandible (3 cases), and nasal septum (2 cases). Autologous adipose tissue was harvested from the anterior abdominal wall, and adipose-derived stem cells were cultured, expanded, and then seeded onto resorbable scaffold materials for subsequent reimplantation into hard-tissue defects. The defects were reconstructed with either bioactive glass or β-tricalcium phosphate scaffolds seeded with adipose-derived stem cells (ASCs), and in some cases with the addition of recombinant human bone morphogenetic protein-2. Production and use of ASCs were done according to good manufacturing practice guidelines. Follow-up time ranged from 12 to 52 months. Successful integration of the construct to the surrounding skeleton was noted in 10 of the 13 cases. Two cranial defect cases in which nonrigid resorbable containment meshes were used sustained bone resorption to the point that they required the procedure to be redone. One septal perforation case failed outright at 1 year because of the postsurgical resumption of the patient's uncontrolled nasal picking habit.

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh: Six-Year Clinical Follow-Up Results

“…We decided to use ASCs mainly because of their great accessibility and low patient morbidity when compared with other mesenchymal cell sources such as bone marrow or periosteum. The in vitro, in vivo and clinical bone‐forming capacity of ASCs in combination with various scaffold materials have been reported by many authors 14, 20, 35, 36, 37, 38, 39, 40, 41. In this series, the flow cytometric characterization of the ASCs expanded in autologous serum corresponded to previously published results for ASCs 42, 43.…”

“…The potential of these cells has evoked great enthusiasm and high expectations in both scientific and commercial circles. However, in general clinical applications of stem cells in reconstructive surgery have been limited to small case series with varying results and/or short follow‐up periods 14, 31, 32, 33. Among the published studies, there is a great variability in, for example, stem cell sources, defect sites and sizes, indications, cell carriers, and use of growth factors that makes it difficult to draw a solid conclusion on stem cell effectiveness in bone tissue engineering 26.…”

“…The grafts seemed to be successful in short‐term follow‐up, both clinically and radiologically, but already the mid‐term results showed increased graft resorption 13, 14. In the current study, our objective is to report the long‐term results (6.1–7.4 years) of this method.…”

“…Our aim was to overcome common problems associated with conventional cranioplasties by creating bone from patients' own adipose‐derived stem cells (ASCs), beta‐tricalcium phosphate (betaTCP) granules and supporting meshes 13, 14. In recent years, ASCs have been under extensive study in regenerative medicine 15, 16, 17, 18.…”

“…They are easily retrieved in high numbers from fat tissue and expanded in vitro, which makes them an attractive tool in tissue reconstruction 14, 19, 20. However, scientific evidence in terms of safety and efficacy of ASC use in regenerative medicine is still limited 14, 20, 21, 22, 23, 24.…”