The Use of Bone Marrow Stromal Cells (Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells) for Alveolar Bone Tissue Engineering: Basic Science to Clinical Translation

Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms

Ischemic culture of dental pulp-derived cells is a useful model in which to investigate mechanisms of post-ischemic tissue recovery

Dental pulp is a soft tissue characterized by unique regenerative properties. It is located in the center of each tooth, and is surrounded by hard tissue (dentin). Vascular access is limited to a small foramen at the root apex. Because of this anatomical limitation, dental pulp can easily lose its blood supply, causing the tissue to become ischemic. This occurs, for example, when a tooth is dislocated by traumatic injury or is subjected to inflammation. Since ischemia is caused by a critical shortage of oxygen and nutrients, ischemic damage is usually irreversible, even when the ischemic event is transient. However, unlike ischemia-sensitive organs such as the brain and heart, dental pulp is relatively ischemia-resistant, and recovers from ischemic injury by regenerating damaged tissue. The mechanisms by which this regeneration occurs are poorly understood, but are being investigated in cell culture models that mimic in vivo ischemic conditions using a combination of hypoxia and nutrient deprivation. Here, we review the use of ischemic cell culture to investigate the mechanisms of post-ischemic dental pulp tissue recovery

Clinical Outcome and 8-Year Follow-Up of Alveolar Bone Tissue Engineering for Severely Atrophic Alveolar Bone Using Autologous Bone Marrow Stromal Cells with Platelet-Rich Plasma and β-Tricalcium Phosphate Granules

Background: Although bone tissue engineering for dentistry has been studied for many years, the clinical outcome for severe cases has not been established. Furthermore, there are limited numbers of studies that include long-term follow-up. In this study, the safety and efficacy of bone tissue engineering for patients with a severely atrophic alveolar bone were examined using autogenous bone marrow stromal cells (BMSCs), and the long-term stability was also evaluated. Methods: BMSCs from iliac bone marrow aspirate were cultured and expanded. Then, induced osteogenic cells were transplanted with autogenous platelet-rich plasma (PRP) and β-tricalcium phosphate granules (β-TCP) for maxillary sinus floor and alveolar ridge augmentation. Eight patients (two males and six females) with an average age of 54.2 years underwent cell transplantation. Safety was assessed by monitoring adverse events. Radiographic evaluation and bone biopsies were performed to evaluate the regenerated bone. Results: The major population of transplanted BMSCs belonged to the fraction of CD34−, CD45dim, and CD73+ cells, which was only 0.065% of the total bone marrow cells. Significant deviations were observed in cell growth and alkaline phosphatase activities among individuals. However, bone regeneration was observed in all patients and the average bone area in the biopsy samples was 41.9% 6 months following transplantation, although there were also significant deviations among each case. No adverse events related to the transplants were observed. In the regenerated bone, 27 out of 29 dental implants were integrated. Dental implants and regenerated bone were stable for an average follow-up period of 7 years and 10 months. Conclusions: Although individual variations were observed, the results showed that bone tissue engineering using BMSCs with PRP and β-TCP was feasible for patients with severe atrophic maxilla throughout a long-term follow-up period and was considered safe. However, further studies with a larger number of cases and controls to confirm the efficacy of BMSCs and the development of a protocol to establish a reproducible quality of stem cell-based graft material will be required