Optimized Cell Survival and Seeding Efficiency for Craniofacial Tissue Engineering Using Clinical Stem Cell Therapy

Abstract

Traumatic injuries involving the face are very common, yet the clinical management of the resulting craniofacial deficiencies is challenging. These injuries are commonly associated with missing teeth, for which replacement is compromised due to inadequate jawbone support. Using cell therapy, we report the upper jaw reconstruction of a patient who lost teeth and 75% of the supporting jawbone following injury. A mixed population of bone marrow-derived autologous stem and progenitor cells was seeded onto b-tricalcium phosphate (b-TCP), which served as a scaffold to deliver cells directly to the defect. Conditions (temperature, incubation time) to achieve the highest cell survival and seeding efficiency were optimized. Four months after cell therapy, cone beam computed tomography and a bone biopsy were performed, and oral implants were placed to support an engineered dental prosthesis. Cell seeding efficiency (>81%) of the b-TCP and survival during the seeding process (94%) were highest when cells were incubated with b-TCP for 30 minutes, regardless of incubation temperature; however, at 1 hour, cell survival was highest when incubated at 4°C. Clinical, radiographic, and histological analyses confirmed that by 4 months, the cell therapy regenerated 80% of the original jawbone deficiency with vascularized, mineralized bone sufficient to stably place oral implants. Functional and aesthetic rehabilitation of the patient was successfully completed with installation of a dental prosthesis 6 months following implant placement. This proof-of-concept clinical report used an evidence-based approach for the cell transplantation protocol used and is the first to describe a cell therapy for craniofacial trauma reconstruction. STEM CELLS

Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial

“…The results of the current clinical study showed that this cell therapy is capable of osseous regeneration, confirming the results of our previous randomized controlled clinical studies where ixmyelocel‐t therapy was evaluated in bone regeneration of extraction sockets and bone reconstruction of maxillary sinuses . In the present study however, the ability of these cells to completely reconstitute a large craniofacial defect was limited, particularly in the patients with cleft palate.…”

“…Our clinical trial was designed to evaluate the safety and efficacy of an The results of the current clinical study showed that this cell therapy is capable of osseous regeneration, confirming the results of our previous randomized controlled clinical studies where ixmyelocel-t therapy was evaluated in bone regeneration of extraction sockets and bone reconstruction of maxillary sinuses. 8,9,11 In the present study however, the ability of these cells to completely reconstitute a large craniofacial defect was limited, particularly in the patients with cleft palate. It is well-established that in patients with large cleft lip and 19,20 Scar tissue may have a poor blood supply with low oxygen tension, and when it is used to cover a bone graft, healing can be compromised.…”

“…In an effort to overcome the limitations of current bone augmentation procedures, cell therapy by means of cell transplantation has emerged as a possible strategy to regenerate alveolar bone. Recently, there have been several clinical reports evaluating the use of stem cells as a promising alternative approach for the reconstruction of alveolar bone defects . We have previously demonstrated that the use of autologous mixed cell populations containing stem cells enhance and accelerate healing and regeneration of bone .…”

“…Recently, there have been several clinical reports evaluating the use of stem cells as a promising alternative approach for the reconstruction of alveolar bone defects. [7][8][9][10][11] We have previously demonstrated that the use of autologous mixed cell populations containing stem cells enhance and accelerate healing and regeneration of bone. 9 Due to success in regenerating localized bone defects, the aim of this study was to evaluate this approach for larger, more challenging alveolar defects.…”

The Current Status of Stem Cell Regeneration in Intra Oral Applications—A Systematic Review

“…Functional and aesthetic rehabilitation of the patient was successfully completed with installation of a dental prosthesis 6 months following implant placement. This proof-of-concept clinical report used an evidence-based approach for the cell transplantation protocol and is the first to describe a cell therapy for craniofacial trauma reconstruction [116].…”