Project: Bone augmentation with autologous adipose tissue-derived mesenchymal stem cells, BMP-2, and calcium phosphate carrier in the human maxillary sinus floor elevation model

Bone augmentation with autologous adipose tissue-derived mesenchymal stem cells, BMP-2, and calcium phosphate carrier in the human maxillary sinus floor elevation model

This is a summary of the request.

A major limiting factor for dental implantations is insufficient alveolar bone height. These cases are currently treated with a maxillary sinus floor elevation procedure, using predominantly iliac crest bone. However, this is associated with a second surgery site and donor site morbidity. Since the sinus floor elevation model is unique by allowing histological examination of biopsies removed prior to abutment implantation, we could demonstrate that bone substitutes showed low bone ingrowth rates. Previous in vitro and large animal studies have shown the feasibility and safety of a novel concept employing bone substitutes in combination with freshly isolated adipose tissue stem cells, which are either or not osteogenically stimulated with physiological dosages of bone morphogenetic protein-2 (BMP-2). This was performed in a two hour one-step surgical procedure within the surgical theatre, thus avoiding costly GMP stem cell expansions and second intervention.

This proposal aims to perform clinical studies evaluating this concept for safety and efficacy within the human sinus floor elevation model, combining clinical outcome with histology. If successful, this offers broad potential for other bone tissue engineering applications.

This new concept overcomes the problems currently encountered with cellular therapies: the need for in vitro expansion, high costs, and repeated surgeries. Moreover, when using non-induced, minimally manipulated cells, many regulatory hurdles are avoided, thereby accelerating clinical introduction. Additional innovative aspects include:

1) freshly isolated, autologous stem cell preparations rich in adipose stem cells (1-10%) are used.

2) BMP-2 triggering of adipose stem cells occurs ex vivo prior to implantation for 15 min only, as already shown to be effective for bone phenotype induction. This avoids in vivo BMP-2 exposure.

3) in this way, ng-range amounts of BMP-2 are effective for osteogenic induction, allowing a cost-effective procedure without concomitant adverse effects observed when applying the current (mg-range) BMP-2 dosages.