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A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism

引用

Journal of Molecular Cell Biology 2022年第2期14卷 56-71页

作者： Lianju Qin Jing Zhang Yujie Xiao Kang Liu Yugui Cui Fangyan Xu Wenkai Ren Yanggang Yuan Chunyan Jiang Song Ning Xiaoxue Ye Ming Zeng Hanyang Qian Anning Bian Fan Li Guang Yang Shaowen Tang Zhihong Zhang Juncheng Dai Jing Guo Qiang Wang Bin Sun Yifei Ge Chun Ouyang Xueqiang Xu Jing Wang Yaoyu Huang Hongqing Cui Jing Zhou Meilian Wang Zhonglan Su Yan Lu Di Wu Jingping Shi Wei Liu Li Dong Yinbing Pan Baiqiao Zhao Ying Cui Xueyan Gao Zhanhui Gao Xiang Ma Aiqin Chen Jie Wang Meng Cao Qian Cui Li Chen Feng Chen Youjia Yu Qiang Ji Zhiwei Zhang Mufeng Gu Xiaojun Zhuang Xiaolin Lv Hui Wang Yanyan Pan Ling Wang Xianrong Xu Jing Zhao Xiuqin Wang Cuiping Liu Ningxia Liang Changying Xing Jiayin Liu Ningning Wang State Key Laboratory of Reproductive Medicine Center of Clinical Reproductive MedicineThe First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Nephrology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical UniversityNanjing 211166China Department of Pathology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Cardiology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Rheumatology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Obstetrics The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Dermatology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Burn and Plastic Surgery The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Nuclear Medicine The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Infection The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Anesthesiology and Pain Management The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Nephrology The First People’s Hospital of LianyungangLianyungang 222061China Department of Nephrology Northern Jiangsu People’s HospitalYangzhou 225001China Department of General Medicine Geriatric Hospital of Nanjing Medical UniversityNanjing 210024China Department of Nephrology BenQ Medical CenterThe Affiliated BenQ Hospital of Nanjing Medical Uni

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.

关键词： calciphylaxis chronic kidney disease vascular calcification multidisciplinary rescue human amnion-derived mesenchymal stem cells preclinical research regenerative medicine

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