טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentNishri Yasmin
SubjectAutologous Cell-Based Approach for Treating Maxillary
Alveolar Bone Defects Caused by Cleft Lip and
Palate
DepartmentDepartment of Biotechnology
Supervisor Clinical Professor Dror Aizenbud


Abstract

Cleft lip (CL) and/or cleft palate (CP) occur due to a failure of the skeletal components of the mid-face to fuse during gestation. This impairment leads to the most prevalent congenital craniofacial birth defect in humans , observed in approximately 1 out of 700 live births. Alveolar cleft is a bony defect that is present in 75% of the patients with cleft lip and palate CLP. Nowadays the most commonly accepted treatment for alveolar repair is autologous secondary alveolar bone grafting from the iliac crest. However, the dissection and exposure of the iliac crest results in trauma to the muscle and fascia attached to it. Moreover, the removal of even a small amount of bone from the iliac crest may result with postoperative pain, gait disturbance and hematoma formation. For these reasons, secondary alveolar bone grafting is often associated with prolonged hospitalization and long recovery. Furthermore, the autologous bone grafts cannot be accurately shaped to fit the missing bone thus compromising the healing process and leaving unaesthetic cavities in the treated patients. An alternative treatment to autologous bone grafting, that is currently being investigated, is cell-based regenerative medicine. This research area focuses on adipose derived stem cells (ADSCs) population that have shown characteristics similar to those of mesenchymal stromal cells (MSCs) found in bone tissue. Their capacity to differentiate along multiple lineage pathways, particularly the osteogenic lineage, combined with their accessibility and availability, renders them as a promising source of cells for bone regenerative medicine. Some cell-based applications involve direct administration of the ADSCs into the target defect site. However, paradigms describing scaffolds loaded with ADSCs are thought to be preferential in guiding bone regeneration by providing support for cell colonization, migration, growth, and differentiation.

Here we show how, with the use of a xeno-free system, a small amount of ADSCs was sufficient to generate a proliferating cell population exhibiting characteristics similar to those of MSCs. Our ability to establish a functional cell-carrier, that led the ADSCs to differentiate towards the osteogenic lineage in a xeno-free environment, facilitates future regulatory aspects. This kind of autologous graft into the alveolar cleft defect may replace the need for complex bone harvesting and eliminate the risk of graft rejection, specifically suitable for alveolar cleft palate treatment.