Author:
Qin Lianju,Zhang Jing,Xiao Yujie,Liu Kang,Cui Yugui,Xu Fangyan,Ren Wenkai,Yuan Yanggang,Jiang Chunyan,Ning Song,Zeng Ming,Yang Guang,Qian Hanyang,Bian Anning,Li Fan,Ye Xiaoxue,Tang Shaowen,Dai Juncheng,Guo Jing,Wang Qiang,Sun Bin,Ge Yifei,Ouyang Chun,Xu Xueqiang,Wang Jing,Huang Yaoyu,Cui Hongqing,Zhou Jing,Wang Meilian,Su Zhonglan,Lu Yan,Wu Di,Zhang Zhihong,Shi Jingping,Liu Wei,Dong Li,Pan Yinbing,Zhao Baiqiao,Cui Ying,Gao Xueyan,Gao Zhanhui,Ma Xiang,Chen Aiqin,Wang Jie,Cao Meng,Cui Qian,Chen Li,Chen Feng,Yu Youjia,Ji Qiang,Zhang Zhiwei,Gu Mufeng,Zhuang Xiaojun,Lv Xiaolin,Wang Hui,Pan Yanyan,Wang Ling,Xu Xianrong,Zhao Jing,Wang Xiuqin,Liu Cuiping,Liang Ningxia,Xing Changying,Liu Jiayin,Wang Ningning
Abstract
AbstractCalciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. We reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers and mummified legs. Because of her rapid progression and refractory to conventional therapy, human amnion-derived mesenchymal stem cells (hAMSCs) treatment was approved. Establishment and release inspection of hAMSCs, efficacy and safety assessment including cytokines secretory ability, immunocompetence, tumorigenicity and genetics analysis in vitro were introduced. We further performed acute and long-term hAMSC toxity evaluations in C57BL/6 mice/rats, abnormal immune response tests in C57BL/6 mice and tumorigenic tests in the neonatal NU nude mice. After pre-clinical research, she was treated by hAMSCs with intravenous and local intramuscular injection and external supernatants application to her ulcers. When followed up to 15 months, her blood-based markers of bone and mineral metabolism were improved, with regeneration of skin soft tissue and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1 month treatment showed vascular regeneration with mature non-calcified vessels within dermis and 20 months later re-epithelialization restored the integrity of damaged site. No infusion or local treatment related adverse events occurred. To the best of our knowledge, this is the first evidence for the clinical use of hAMSCs. These findings suggest hAMSCs warrant further investigation as a potential regenerative treatment for uremic calciphylaxis with effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multi-differentiation, re-epithelialization and restorage of integrity.
Publisher
Cold Spring Harbor Laboratory