Bone Engineering of Maxillary Sinus Bone Deficiencies Using Enriched CD90+ Stem Cell Therapy: A Randomized Clinical Trial

Abstract

Bone engineering of localized craniofacial osseous defects or deficiencies by stem cell therapy offers strong prospects to improve treatment predictability for patient care. The aim of this phase 1/2 randomized, controlled clinical trial was to evaluate reconstruction of bone deficiencies of the maxillary sinus with transplantation of autologous cells enriched with CD90þ stem cells and CD14þ monocytes. Thirty human participants requiring bone augmentation of the maxillary sinus were enrolled. Patients presenting with 50% to 80% bone deficiencies of the maxillary sinus were randomized to receive either stem cells delivered onto a b-tricalcium phosphate scaffold or scaffold alone. Four months after treatment, clinical, radiographic, and histologic analyses were performed to evaluate de novo engineered bone. At the time of alveolar bone core harvest, oral implants were installed in the engineered bone and later functionally restored with dental tooth prostheses. Radiographic analyses showed no difference in the total bone volume gained between treatment groups; however, density of the engineered bone was higher in patients receiving stem cells. Bone core biopsies showed that stem cell therapy provided the greatest benefit in the most severe deficiencies, yielding better bone quality than control patients, as evidenced by higher bone volume fraction (BVF; 0.5 versus 0.4; p ¼ 0.04). Assessment of the relation between degree of CD90þ stem cell enrichment and BVF showed that the higher the CD90 composition of transplanted cells, the greater the BVF of regenerated bone (r ¼ 0.56; p ¼ 0.05). Oral implants were placed and restored with functionally loaded dental restorations in all patients and no treatment-related adverse events were reported at the 1-year follow-up. These results provide evidence that cell-based therapy using enriched CD90þ stem cell populations is safe for maxillary sinus floor reconstruction and offers potential to accelerate and enhance tissue engineered bone quality in other craniofacial bone defects and deficiencies (Clinicaltrials.gov NCT00980278).

What is the clinical applicability of regenerative therapies in dentistry?

“…These therapies, although recent, have been extensively studied over the last two decades. Several in vivo study models have been developed and conducted using many cell lines 1,2,36,38,40 . Synthetic and natural scaffolds have been developed and applied successfully 16,24,26 .…”

“…Regeneration of bone tissue may be an interesting strategy in cases of maxillary corrections after trauma, implant-supported rehabilitation, in regions with atrophic bone tissue, and in the filling of bone defects or in intraosseous pathologies [36][37][38] . Although the incorporation of active compounds into titanium surfaces, for example, may increase biological tissue activity 39 , the direct application of stem cells, mainly from adipose tissue and bone marrow, has produced excellent results [36][37] .…”

“…Although the incorporation of active compounds into titanium surfaces, for example, may increase biological tissue activity 39 , the direct application of stem cells, mainly from adipose tissue and bone marrow, has produced excellent results [36][37] . Most of the studies seeking bone regeneration in the maxillomandibular region have used BMSC from the iliac crest 36 . Kaigler et al 36 undertook a randomized clinical trial with thirty patients who underwent surgery for maxillary sinus augmentation.…”

“…Most of the studies seeking bone regeneration in the maxillomandibular region have used BMSC from the iliac crest 36 . Kaigler et al 36 undertook a randomized clinical trial with thirty patients who underwent surgery for maxillary sinus augmentation. Scaffolds of β-tricalcium phosphate seeded with autologous BMSC were used in sinus elevation.…”

“…Four months after implantation, radiographic analysis did not show any difference in terms of bone gain, but a higher bone density was evidenced in patients who underwent cellular therapies with BMSC. After one year, implant placement surgeries were performed and the bone tissue removed during surgery was analyzed, demonstrating higher bone quality in patients who used BMSC 36 . Another similar study using BMSC, now combined with injectable PRP as a scaffold, also observed favorable results.…”