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

Previous in vitro and large animal studies within our laboratory have shown
feasibility and safety of a novel concept employing bone substitutes in
combination with freshly isolated adipose tissue stem cells, which can be
harvested in a short time frame yielding clinically relevant numbers of
mesenchymal stem cell-like regenerative cells. The whole one-step surgical
procedure could be performed in 2 hours within the surgical theatre, thus
avoiding costly GMP stem cell expansions and second intervention. Clinical
studies are now needed to evaluate 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.

> Primary Objective:
This is a pilot study, aiming at the clinical evaluation with respect to safety
and feasibility of a one-step surgical procedure for maxillary sinus floor
augmentation for the placement of dental implants, using a ceramic bone
substitute seeded with freshly isolated autologous mesenchymal stem cells
derived from adipose tissue
> Secondary Objective(s):
Histological evaluation from biopsies obtained with hollow drills, routinely
collected during the insertion of the dental implants, six months after sinus
floor elevation

This pilot study will be an exploratory, randomized, open, placebo-controlled
phase I intervention study.

There will be three surgical interventions:
1. Sinus floor elevation procedure: This intervention will consist of two arms:
In the first arm, the acquisition of abdominal adipose tissue, its automated
processing using a CE-marked device to obtain the stem cell preparation, and
its subsequent seeding on a calcium phosphate (CaP) scaffold to generate the
bioactive implant. In a parallel arm, a routine sinus floor elevation procedure
is performed by the Oral maxillofacial surgeon. These two arms are combined, as
the surgeon inserts the bioactive scaffold material in the patient*s sinus
cavity. The comparator group will receive CaP which is *seeded* with vehicle
(ringers lactate solution) only. The remainder of the cells will be used for in
vitro characterizations.
2. The 2nd intervention (6 months later) consists of the placement of dental
implants by using hollow trephine drills. These drillings produce bone
biopsies, which will be evaluated histologically / histomorphometrically.
3. The 3rd intervention encompasses the placement of the final fixed prostheses
(crowns or bridges) on the dental implants

The procurement of the SVF and seeding on the scaffold has been the subject of
extensive pre-clinical research. Re-implantation of the seeded scaffolds does
not differ from the normal sinus floor elevation procedure, with which there is
vast experience. In our preclinical studies and in recent reports on the use of
mesenchymal stem cells from bone marrow and caP scaffolds in sinus floor
elevation procedures no adverse effects were documented. Thus,
post-implantation complications other than those associated with the standard
sinus elevation procedure (infections [<10% of cases], massive loss of graft [<
1% of cases] and occurrence of voids or graft fragmentation [seldom]) are not
expected.
All previous and current human studies of transplanted cells, have involved the
use of autologous or allogenic cells that required ex vivo expansion of the
cells, which is costly, time-consuming and strictly regulated, making it an
intricate procedure. By utilizing the Celution® 800 technology of Cytori
Therapeutics, Inc., freshly isolated autologous adipose stem cell preparations
(stromal vascular fraction, SVF) will be generated through minimal manipulation
of the tissue and cells. Clinical costs may also be reduced, as the number and
duration of hospital admissions may be diminished, and the need for expensive
stem cell culture facilities is eliminated.