Small blood stem cells for enhancing early osseointegration formation on dental implants: a human phase I safety study.

BACKGROUND: Small blood stem cells (SB cells), isolated from human peripheral blood, demonstrated the ability to benefit bone regeneration and osseointegration. The primary goal of our study is to examine the safety and tolerability of SB cells in dental implantation for human patients with severe bone defects. METHODS: Nine patients were enrolled and divided into three groups with SB cell treatment doses of 1 × 105, 1 × 106, and 1 × 107 SB cells, and then evaluated by computed tomography (CT) scans to assess bone mineral density (BMD) by Hounsfield units (HU) scoring. Testing was conducted before treatment and on weeks 4, 6, 8, and 12 post dental implantation. Blood and comprehensive chemistry panel testing were also performed. RESULTS: No severe adverse effects were observed for up to 6-month trial. Grade 1 leukocytosis, anemia, and elevated liver function were observed, but related with the patient's condition or the implant treatment itself and not the transplantation of SB cells. The levels of cytokines and chemokines were detected by a multiplex immunological assay. Elevated levels of eotaxin, FGF2, MCP-1, MDC, and IL17a were found among patients who received SB cell treatment. This observation suggested SB cells triggered cytokines and chemokines for local tissue repair. To ensure the efficacy of SB cells in dental implantation, the BMD and maximum stresses via stress analysis model were measured through CT scanning. All patients who suffered from severe bone defect showed improvement from D3 level to D1 or D2 level. The HU score acceleration can be observed by week 2 after guided bone regeneration (GBR) and prior to dental implantation. CONCLUSIONS: This phase I study shows that treatment of SB cells for dental implantation is well tolerated with no major adverse effects. The use of SB cells for accelerating the osseointegration in high-risk dental implant patients warrants further phase II studies. TRIAL REGISTRATION: Taiwan Clinical Trial Registry ( SB-GBR001 ) and clinical trial registry of the United States ( NCT04451486 ).