体外扩增自体脂肪干细胞对空鼻综合征患者黏膜功能重建的临床研究

Clinical studies on the ex-vivo expansion of autologous adipose derived stem cells for the functional reconstruction of mucous membrane in empty nose syndrome

目的分析、评估采用自体脂肪干细胞（ASCs）重建空鼻综合征（ENS）患者鼻黏膜功能的可行性和有效性。方法选取2013年8月-2014年2月武警总医院收治的ENS患者5例,每例患者抽取自体脂肪组织15～20ml,于体外进行脂肪干细胞的分离、培养,扩增至第3代时进行细胞免疫表型、分化情况及遗传稳定性鉴定。对有鼻甲残留的ENS患者（n=3）,在鼻黏膜受损处进行ASCs注射移植,隔10日1次,共4次;对无鼻甲残留的ENS患者（n=2）,在鼻黏膜受损处进行ASCs注射移植3次后,抽取其自体单纯脂肪颗粒1～5ml,与第3～6代ASCs混合后行鼻内下鼻甲或中鼻甲成形术。治疗前和治疗后3、6、9个月行鼻内镜检查前后对比,SNOT-20问卷调查、鼻声阻力和鼻黏膜纤毛清除功能所得数据进行统计学分析。结果 2例无鼻甲残留ENS患者行第3～6代ASCs注射移植及3例有鼻甲残留的ENS患者行ASCs联合脂肪颗粒移植后3、6、9个月,鼻内镜检查显示鼻甲成形无明显吸收,鼻腔黏膜明显改善,SNOT-20评分亦明显改善,差异有统计学意义（P〈0.05）。与治疗前比较,5例患者鼻甲成形术后鼻声阻力和鼻黏膜纤毛清除功能无明显变化（P〉0.05）。结论采用脂肪干细胞联合自体脂肪移植行鼻甲成形术重建黏膜功能,可明显改善ENS患者的症状,且效果稳定,是一种新的有助于ENS黏膜修复的治疗方法。

Objective To analyze and evaluate the feasibility and ef ectiveness of using autologous adipose derived stem cells（ASCs） for rebuilding the function of nasal mucosa in patients with empty nose syndrome（ENS）. Methods Autologous adipose tissue 15-20 ml were obtained from each of 5 ENS patients admitted from Aug. 2013 to Feb. 2014, and from which stem cells were isolated, cultured and expanded in vitro. h e phenotype, dif erentiation, and genetic stability of the third generation of amplii ed stem cells were identii ed. For the patients with rudimental turbinate（n=3）, ASCs were injected into the damaged nasal mucosa for 4 times（once every 10 days）. For the patients with no rudimental turbinate（n=2）, autologous pure fat granules 1-5ml were extracted at er 3 times of ASCs injection into the damaged nasal mucosa, and mixed with the 3rd-6th generation of ASCs for inferior or middle nasal turbinate angioplasty. Nasal endoscopic examination was performed before treatment and 3, 6 and 9 months after treatment for comparison, and the data of SNOT-20 questionnaire, nasality resistance and nasal mucociliary clearance action were statistically analyzed. Results With injection transplantation of the 3rd-6th generation of ASCs in 2 patients with no rudimental turbinate, and 3, 6 and 9 months at er the combined ASCs and fat granules transplantation in 3 patients with rudimental turbinate, nasal endoscopy showed that no obvious absorption in conchoplasty, nasal mucosa was improved significantly, and same as SNOT-20 scores, with statistically significant difference（P〉0.05）. Compared with the condition before treatment, no signii cant change was found on the nasality resistance and nasal mucociliary clearance action in the 5 patients at er nasal turbinate angioplasty（P〈0.05）. Conclusions h e reconstruction of mucosa function by nasal turbinate angioplasty combined with adipose derived stem cells and autologous adipose transplantation may signii cantly improve the symptoms in patients with ENS with lasting ef ects. It is a new procedure which is helpful for the mucosal repair in patients with ENS.