用于增强牙种植体早期骨整合形成的小血液干细胞：一项人体 I 期安全性研究。
Small blood stem cells for enhancing early osseointegration formation on dental implants: a human phase I safety study.
机构信息
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Division of Prosthodontics, Department of Dentistry, Taipei Medical University Hospital, Taipei, 110, Taiwan.
出版信息
Stem Cell Res Ther. 2021 Jul 2;12(1):380. doi: 10.1186/s13287-021-02461-z.
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 × 10, 1 × 10, and 1 × 10 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 ).
背景
从小鼠外周血中分离得到的小血干细胞（SB 细胞），具有促进骨再生和骨整合的能力。本研究的主要目的是评估 SB 细胞在治疗严重骨缺损的人类患者牙种植中的安全性和耐受性。
方法
共纳入 9 例患者，分为 3 组，分别给予 1×10、1×10和 1×10 SB 细胞治疗，然后通过 CT 扫描评估骨矿物质密度（BMD），用 Hounsfield 单位（HU）评分进行评估。在治疗前、牙种植后第 4、6、8 和 12 周进行检测。还进行了血液和综合化学小组检测。
结果
在长达 6 个月的试验中，未观察到严重的不良反应。观察到 1 级白细胞增多、贫血和肝功能升高，但与患者病情或植入物治疗本身有关，而与 SB 细胞移植无关。通过多重免疫分析检测细胞因子和趋化因子水平。接受 SB 细胞治疗的患者中发现嗜酸性粒细胞趋化因子、FGF2、MCP-1、MDC 和 IL17a 水平升高。这一观察结果表明，SB 细胞触发了局部组织修复的细胞因子和趋化因子。为了确保 SB 细胞在牙种植中的疗效，通过 CT 扫描测量了骨密度和最大应力的应力分析模型。所有患有严重骨缺损的患者均从 D3 级改善到 D1 级或 D2 级。在引导骨再生（GBR）后第 2 周和牙种植前即可观察到 HU 评分的加速。
结论
这项 I 期研究表明，牙种植中使用 SB 细胞治疗具有良好的耐受性，无主要不良反应。在高风险牙种植患者中使用 SB 细胞加速骨整合值得进一步进行 II 期研究。
试验注册
台湾临床试验注册中心（SB-GBR001）和美国临床试验注册中心（NCT04451486）。
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