人羊膜间充质干细胞多学科救治钙化防御病及再生机制探讨  

Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion‑derived mesenchymal stem cells

作　　者：王宁宁 覃莲菊 刘康 邢昌赢 张静[1] 肖雨洁 崔毓桂 宁松 袁杨刚 鲁严 张智泓 苏忠兰 叶笑雪 卞安宁 曾鸣 王嫱 徐方燕 任文凯 吕小林 王玲 赵静 王美莲 马翔 刘翠萍 汪秀琴 梁宁霞 刘嘉茵 Wang Ningning;Qin Lianju;Liu Kang;Xing Changying;Zhang Jing;Xiao Yujie;Cui Yugui;Ning Song;Yuan Yanggang;Lu Yan;Zhang Zhihong;Su Zhonglan;Ye Xiaoxue;Bian Anning;Zeng Ming;Wang Qiang;Xu Fangyan;Ren Wenkai;Lyu Xiaolin;Wang Ling;Zhao Jing;Wang Meilian;Ma Xiang;Liu Cuiping;Wang Xiuqin;Liang Ningxia;Liu Jiayin(Department of Nephrology,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;State Key Laboratory of Reproductive Medicine,Center of Clinical Reproductive Medicine,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210036,China;Department of Dermatology,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;Department of Pathology,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;Department of Rheumatology,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;Department of Outpatient,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029 China;Department of Obstetrics,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029 China;Department of Biological Specimen Repository,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029 China;Department of International Cooperation,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;Academy of Clinical and Translational Research,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院江苏省人民医院肾内科,南京210029 [2]南京医科大学第一附属医院江苏省人民医院生殖医学国家重点实验室临床生殖医学中心,南京210036 [3]南京医科大学第一附属医院江苏省人民医院皮肤科,南京210029 [4]南京医科大学第一附属医院江苏省人民医院病理科,南京210029 [5]南京医科大学第一附属医院江苏省人民医院风湿免疫科,南京210029 [6]南京医科大学第一附属医院江苏省人民医院门诊部,南京210029 [7]南京医科大学第一附属医院江苏省人民医院产科,南京210029 [8]南京医科大学第一附属医院江苏省人民医院生物样本库,南京210029 [9]南京医科大学第一附属医院江苏省人民医院国际合作部,南京210029 [10]南京医科大学第一附属医院江苏省人民医院临床与转化研究院,南京210029

出　　处：《中华医学杂志》2022年第28期2217-2221,共5页National Medical Journal of China

基　　金：国家自然科学基金(81730041,81671447,81570666);国家重点研发项目(2017YFC1001303);国际肾脏病学会(ISN)临床研究项目(18‑01‑0247);江苏省临床医学中心项目(YXZXB2016001、BL2012009);生殖医学国家重点实验室创新项目(SKLRM‑GC201803);中华国际交流基金会肾性贫血科研基金(Z‑2017‑24‑2037);江苏省卫生厅项目(H201605);江苏省临床医学研究中心支撑体系建设(BL2014084);江苏省“医学重点人才”项目(ZDRCA2016002);南京医科大学第一附属医院(江苏省人民医院)优秀中青年人才支持计划。

摘　　要：钙化防御病罕见且死亡率高,因皮肤缺血坏死和感染导致剧痛,尚缺乏有效治疗方法。常发生在终末期肾病(ESKD)患者,又称钙化性尿毒症性小动脉病(CUA),组织学特征是真皮微血管钙化、内膜纤维增生和微血栓形成。本文创新性运用人羊膜间充质干细胞(hAMSCs)多学科再生治疗1例34岁尿毒症女性患者,其臀部、双下肢广泛进行性溃疡,伴剧痛和恶臭分泌物,皮肤病理符合钙化防御病。患者因常规治疗无效,经医院伦理委员会批准行hAMSCs抢救性治疗,包括静脉和局部肌内注射、创面外敷hAMSCs培养上清液。患者的皮肤和软组织再生,血生化、炎症、矿物质和骨代谢指标、免疫功能紊乱好转。患者的视觉模拟疼痛量表治疗前为10分、治疗15个月为0分;Bates‑Jensen伤口评价量表治疗前为65分、治疗15个月为13分;伤口生活质量调查问卷治疗前为68分、治疗15个月为0分。hAMSCs治疗CUA具有良好的应用前景,机制可能与抑制血管钙化、促进新生血管和皮肤软组织再生修复、抗炎及免疫调节等有关。Calciphylaxis is a rare disease with severe pain and high‑mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies.The occurrence of calciphylaxis in end stage kidney disease(ESKD)patients is known as calcific uremic arteriolopathy(CUA),which is characterized histologically by dermal microvessel calcification,intimal fibroplasia and microthrombosis.Here we innovatively treated a severe CUA patient with human amnion‑derived mesenchymal stem cells(hAMSCs).A 34‑year‑old uremic woman was presented with progressive,painful malodorous ulcers in buttocks and mummified lower limbs.Skin pathological features supported the diagnosis of calciphylaxis.The patient was refractory to conventional multidisciplinary symptomatic therapies.With the approval of our hospital ethics committee,she was treated with hAMSCs including intravenous and local intramuscular injection,and external application of hAMSC culture supernatant to the wound area.During 15‑month follow‑up,the patient had regeneration of skin and soft tissues,with improved blood biochemical,inflammatory,mineral and bone metabolic indices and immunoregulation effects.After 15‑month hAMSC treatment,the score of pain visual analog scale(VAS)decreased from 10 to 0,Bates‑Jensen wound assessment tool(BWAT)score decreased from 65 to 13,and wound‑quality of life(Wound‑QoL)questionnaire score decreased from 68 to 0.We propose that hAMSC treatment is promising for CUA patients.The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,modulating adverse inflammatory and immunologic responses,promoting re‑epithelialization and restoring skin integrity.

关 键 词：羊膜 间充质干细胞 慢性肾功能不全 钙化防御病 再生医学 

分 类 号：R692.5[医药卫生—泌尿科学]